MARCH 29, 1901.] 
still in early progress in another. In fact 
the phase has no exact boundary in time. 
During the second, later and much longer 
period or phase of development, the multi- 
plication of nuclei lags behind the growth 
of the protoplasm ; the increase is gradual 
and often shows itself through successive 
generations of cells, sometimes, however, in 
a single cell, which no longer multiplies. 
OF the first method of protoplasmic growth 
embryonic blood-cells offer a good illustra- 
tion, of the second the neuroblasts or young 
nerve cells afford a striking example. Now 
cells of the embryonic type show little if 
any capacity for differentiation, and the in- 
crease of the protoplasm in the single cell 
is, So far as we can judge, a necessary pre- 
liminary step to cell differentiation. The 
embryonic cells have yet another character- 
istic of basal significance ; they are capable 
of rapid multiplication. Hence we con- 
clude that the growth of the cytoplasm im- 
pedes the multiplication of cells, and, there- 
fore, ultimately retards the growth of the 
body, as a whole, while on the other hand 
it favors differentiation. Accordingly the 
growth of cells and their differentiation 
are essentially antagonistic processes, which 
are necessarily more or less mutually exclu- 
sive. This conclusion which I published 
in 1890, has since been amply confirmed by 
further observation. It is probably appli- 
eable alike to animals and plants, alike to 
normal and abnormal tissues. It is one of 
the many conclusions of embryology which 
are sure to throw a revealing light upon 
some of the dark problems of pathology. 
During the first phase of development, 
as just defined, we encounter preparatory 
changes which we may characterize sum- 
marily as the manufacture of embryonic 
cells. During the second phase, though 
the production of embryonic cells is doubt- 
less continued in certain regions, there 
supervenes the process of differentiation, 
the true histogenesis. 
SCIENCE. 
485 
After segmentation there follows the 
formation of the germ layers, a gradual 
arrangement of the cells in three distinet 
primary strata—at least in all vertebrates 
there are always three strata, never more * 
nor less. The outer and inner layers, ecto- 
derm and entoderm, very early become dis- 
tinetly epithelial. The middle layers be- 
come partly epithelial, partly of a special 
character, that is mesenchymal. At first 
one is inclined to think of the difference 
between epithelium and mesenchyma as a 
fundamental one, an early and unalterable 
separation of cells into classes. This view 
finds support in the fact that the mesen- 
chyma, and it only, produces in the course 
of further development the connective tis- 
sue and supporting tissues of the adult. 
- More attentive study of the germ layers in 
early stages reveals, however, that the 
mesenchymal cells arise from the epithe- 
lium, single epithelial cells migrating from 
the parent territory, while on the other 
hand groups of mesenchymal cells rear- 
range themselves so as to form an epithelial 
covering of some surface, as for example, in 
synovial cavities, arachnoid spaces, the 
inner surface of the cornea, lymph vessels, 
ete. Such observations teach us that we 
must not assume that either the form or 
the arrangement of cells is necessarily and 
always a sign of true differentiation, but 
that instead we are to conceive of differen- 
tiation as a change in the intimate and es- 
sential structure of the individual cell, more 
specifically of its protoplasm, and perhaps 
of its nucleus. The réle of nuclei in his- 
togenesis is a topic which unfortunately is 
still awaiting serious investigation. To 
resume: it seems to me probable that the 
cells of the germ layers are at first quite 
* Hertwig and some other German embryologists 
divide the mesoderm into two layers ; the division is 
contrary to the actual development, and is made, in 
my opinion, quite arbitrarily to satisfy the needs of an 
erroneous theory. 
