132 
Proceedings of the Royal Society of Edinburgh. [Sess. 
(It is worthy of note that in one case, Observation B 3, the removal of 
the ovaries from two young bitches was attended by generally similar 
results.) 
SECTION II.— HISTOLOGICAL AND PHYSIOLOGICAL. 
The histological facts of the process of endochondral ossification are 
universally known, but their metabolic interpretation is not. A short state- 
ment of the writer’s views on the subject is therefore necessary as a 
preliminary to the complete discussion of the nature of the changes in the 
environment of the somatic cells induced by ablation of the testicles. 
1. The Histology of Endochondral Ossification in terms 
of Metabolism. 
In an embryo of the second month the mesoblastic cells which are 
placed in the axis of each limb bud become crowded together to form the 
cartilage which maps out the developing bone. After a time the cells 
situated near the centre of the mass gradually but progressively hyper- 
trophy, and by their hypertrophy mark histologically the centre of 
ossification. 
It is a commonplace that the surface of a sphere increases as the square, 
the content as the cube of its diameter. It follows that, as the hypertrophy 
of a cell continues, its surface area must become progressively smaller in 
proportion to its mass, and eventually must become too small to support 
that mass. The cell must then divide or die. 
These simple facts are expressed in the cytological law : “ The early 
growth of a cell, the increasing bulk of contained protoplasm, the accumula- 
tion of nutritive material, correspond to a predominance of protoplasmic 
processes which are constructive or anabolic. The growing disproportion 
between mass and surface must, however, imply a relative decrease of 
anabolism. Yet the life or general metabolism continues, and this entails 
a gradually increasing preponderance of destructive processes, or katabolism. 
So long as growth continues, the algebraic sum of the protoplasmic processes 
must be plus on the side of anabolism. The limit of growth, when waste 
was overtaken and is beginning to exceed the income or repair, corresponds 
in the same way to the maximum of katabolic preponderance consistent 
with life ” (30). 
In other words, the growth of a cell varies directly as the surplus of 
nutrition over expenditure, and directly as the rate at which this surplus 
decreases. The moment the surplus falls below zero, the cell must 
degenerate and die. This is the metabolic explanation of the histological 
