culties with which they had to contend. The microtome, the microscope, and differential staining methods, in their present-day perfection did not exist for them. It was the day of the razor and hand sectioning. The first microtome appears to have been that used by Professor His in 1866; the improvements leading to the perfection of the present-day microtome did not begin until 1875. The development of the objective of the compound microscope was just beginning in Schwann's time (1830). Although iodine was early used, it was not until about 1857 that Geleach called attention to carmine, the first nuclear stain to be introduced into histological technic. At first, tissues were examined only in the fresh state and even later when hardened they were not imbedded as now in celloidin or paraffin, but placed between vegetable pith or blocks of amyloid organs during the process of cutting.
Surely the technical difficulties were great and we are not surprised that both Schleiden and Schwann believed new cells to be formed through a process of "crystallization" from a "mother liquor" or cytoblastema and that the cell was a vesicle with a solid wall. This question of minute structure and that of mitosis yielded eventually to improvements in tecnnique and Schleiden's theory of the formation of cells de novo was discarded, and we know from Virchow's famous aphorism "omnis cellula e cellula" that in his time it was established that cells arose only by the division of preexisting cells. This general law was the result largely of the work of botanists, as Hugo von Mohl and Nägeli, and was applied by Virchow (1858) to animal tissues only after much work had been done on such tissues by Kölliker, Reichert and Remak. It was not until 1873 (Anton Schneider) that an insight into the details of cell division was gained and it was 1882 when the part of the nucleus in karyokinesis was satisfactorily demonstrated and Flemming could supplement Virchow's aphorism with another "omnis nucleus e nucleo."
Thus did Schleiden, a botanist of the University of Jena, and Schwann, assistant (1824r-1838) to Müller, establish one of the most brilliant and most important generalizations of the century, which became at once the basis of all morphological studies, and, as applied by Virchow, placed pathology on a scientific basis, and has continued as a result of its general biological applications—to development, inheritance and immunity—to influence medicine profoundly. As Verworn has said:
It will be necessary to return to the cell theory again in discussing