PULMONARY EVOLUTION IN MAMMALIA 159 
A. Structural modifications of the primitive lung-sacs 
The further development of the primitive smooth walled lung- 
tube depends upon two subsequent changes: 
I. With the extension of the lung-sac its circumference de- 
velops points of increased epithelial proliferation. These areas 
of heightened mitotic activity protrude as hollow epithelial buds, 
whose lumina are in open communication with the central cavity 
of the lung-sac. The latter thus becomes studded with closely 
aggregated pulmonary vesicles or crypts (fig. 7”). 
The lung of the Anure amphibian (Rana) furnishes a good 
example of this phyletic stage. 
As the surface area of the lung-sac increases the previous uni- 
form budding of the pulmonary vesicles is replaced by a smaller 
number of localized areas of more intensive proliferation, which 
develop into sac-like protrusions. By continued centrifugal bud- 
ding from their walls these repeat in every detail the structure 
of the primitive vesiculated lung-sac, and initiate the subdivision 
of the original wide pulmonary cavum into a number of cham- 
bers (fig. 7°). The walls of the adjacent compartments come 
into contact by their mesodermal investment and fuse. The 
lung now is seen on section to be divided into a series of pockets 
by septa, apparently arising from the surface and directed toward 
the center of the original pulmonary cavum, into whose axial 
remnant the individual pockets open by wide mouths. The fused 
walls of the original centrifugally developed outgrowths from the 
primitive lung-sac carry the mesodermal blood vessels in the 
resulting septa. The multiple components of this advancing 
lung have, like the antecedent primitive lung-sac from which 
they arose, the capacity to initiate from their entodermal lining 
epithelial buds, each one of which is equivalent to one of the or- 
iginal points of proliferation from the primary lung-sac respons- 
ible for the production of the entire generation of the secondary 
sacs. The lung now contains a central tubular space, the reduced 
pulmonary cavum of the primitive lung-sac, which leads by a 
number of passages ventrad and dorsad into a corresponding 
number of secondary chambers, each a replica of the entire prim- 
