nucleus underwent cleavage, and that each of its divisions entered into the formation of a new cell. By these observations, and by others subsequently made, it became obvious that the multiplication of animal cells, either by division of the nucleus within the cell, or by the budding off of a part of the protoplasm of the cell, was to be regarded as a widely spread and probably a universal process, and that each new cell arose from a parent cell.

Pathological observers were, however, for the most part inclined to consider free cell-formation in a blastema or exudation by an aggregation of molecules, in accordance with the views of Henle, as a common phenomenon. This proposition was attacked with great energy by Virchow in a series of memoirs published in his ‘Archiv,’ commencing in Vol. 1, 1847, and finally received its death-blow in his published lectures on Cellular Pathology, 1858. He maintained that in pathological structures there was no instance of cell development de novo; where a cell existed, there one must have been before. Cell-formation was a continuous development by descent, which he formulated in the expression omnis cellula e cellulâ.

KARYOKINESIS.

While the descent of cells from preëxisting cells by division of the nucleus during the development of the egg, in the embryos of plants and animals, and in adult vegetable and animal tissues, both in healthy and diseased conditions, had now become generally recognized, the mechanism of the process by which the cleavage of the nucleus took place was for a long time unknown. The discovery had to be deferred until the optician had been able to construct lenses of a higher penetrative power, and the microscopist had learned the use of coloring agents capable of dyeing the finest elements of the tissues. There was reason to believe that in some cases a direct cleavage of the nucleus, to be followed by a corresponding division of the cell into two parts, did occur. In the period between 1870 and 1880 observations were made by Schneider, Strasburger, Bütschli, Fol, van Beneden and Flemming, which showed that the division of the nucleus and the cell was due to a series of very remarkable changes, now known as indirect nuclear and cell division, or karyokinesis. The changes within the nucleus are of so complex a character that it is impossible to follow them in detail without the use of appropriate illustrations. I shall have to content myself, therefore, with an elementary sketch of the process.

I have previously stated that the nucleus in its passive or resting stage contains a very delicate network of threads or fibers. The first stage in the process of nuclear division consists in the threads arranging themselves in loops and forming a compact coil within the nucleus. The coil then becomes looser, the loops of threads shorten and thicken, and somewhat later each looped thread splits longitudinally into two portions. As the threads stain when coloring agents are applied to them, they are called chromatin fibers, and the loose coil is the chromosome (Waldeyer).

As the process continues, the investing membrane of the nucleus disappears, and the loops of threads arrange themselves within the nucleus so that the closed ends of the loops are directed to a common center, from which the loops radiate outwards and produce a starlike figure (aster). At the same time clusters of extremely delicate lines appear both in the nucleoplasm and in the body of the cell, named the achromatic figure, which has a spindle-like form with two opposite poles, and stains much more feebly than the chromatic fibers. The loops of the chromatic star then arrange themselves in the equatorial plane of the spindle, and bending round turn their closed ends towards the periphery of the nucleus and the cell.

The next stage marks an important step in the process of division of the nucleus. The two longitudinal portions, into which each looped thread had previously split, now separate from each other, and whilst one part migrates to one pole of the spindle, the other moves to the opposite pole, and the free ends of each loop are directed toward its equator (metakinesis). By this division of the chromatin fibers, and their separation from each other to opposite poles of the spindle, two starlike chromatin figures are produced (dyaster).

Each group of fibers thickens, shortens, becomes surrounded by a membrane, and forms a new or daughter nucleus (dispirem). Two nuclei therefore have arisen within the cell by the division of that which had previously existed, and the expression formulated by Flemming—omnis nucleus e nucleo—is justified. Whilst this stage is in course of being completed, the body of the cell becomes constricted in the equatorial plane of the spindle, and, as the constriction deepens, it separates into two parts, each containing a daughter nucleus, so that two nucleated cells have arisen out of a preëxisting cell.

A repetition of the process in each of these cells leads to the formation of other cells, and, although modifications in details are found in different species of plants and animals, the multiplication of cells in the egg and in the tissues generally on similar lines is now a thoroughly established fact in biological science.

In the study of karyokinesis, importance has been attached to the number of chromosomes in the nucleus of the cell. Flemming had seen in the Salamander twenty-four chromosome fibers, which seems to be a constant number in the cells of epithelium and connective tissues. In other cells, again, especially in the ova of certain animals, the number is smaller, and fourteen, twelve, four and even two only have been described. The theory formulated by Boveri that the number of chromosomes is constant for each species, and that in the karyokinetic figures corresponding numbers are found in homologous cells, seems to be not improbable.

In the preceding description I have incidentally referred to the appearance in the proliferating cell of an achromatic spindle-like figure. Although this was recognized by Fol in 1873, it is only during the last ten or twelve years that attention has been paid to its more minute arrangements and possible signification in cell-division.

The pole at each end of the spindle lies in the cell plasm which surrounds the nucleus. In the center of each pole is a somewhat opaque spot (central body) surrounded by a clear space, which, along with the spot, constitutes the centrosome of the sphere of attraction. From each centrosome extremely delicate lines may be seen to radiate in two directions. One set extends towards the pole at the opposite end of the spindle, and, meeting or coming into close proximity with radiations from it, constitutes the body of the spindle, which, like a perforated mantle, forms an imperfect envelope around the nucleus during the process of division. The other set of radiations is called the polar and extends in the region of the pole towards the periphery of the cell.

The question has been much discussed whether any constituent part of the achromatic figure, or the entire figure, exists in the cell as a permanent structure in its resting phase; or if it is only present during the process of karyokinesis. During the development of the egg the formation of young cells, by division of the segmentation nucleus, is so rapid and continuous that the achromatic figure, with the centrosome in the pole of the spindle, is a readily recognizable object in each cell. The polar and spindle-like radiations are in evidence during karyokinesis, and have apparently a temporary endurance and function. On the other hand, van Beneden and Boveri were of opinion that the central body of the centrosome did not disappear when the division of the nucleus came to an end, but that it remained as a constituent part