May 17, 1901.] 
formation of the zymogen granules, and 
that these, in turn, ultimately give rise to 
the soluble ferments. In this connection, 
it might be well to recall the interesting 
histological investigations of Heidenhain 
on the pancreas of the dog during the dif- 
ferent phases of nutrition. In the case of 
a dog that had been fasting for a little over 
one day, each cell of this gland was seen to 
consist of two zones. The inner zone, 
abutting on the lumen of the alveolus, was 
observed to be much the larger of the two 
and to be thickly studded with fine gran- 
ules, while the outer one, towards the 
basement membrane, was narrow and its 
substance clear and homogeneous. The 
nucleus of the cell was observed to be 
considerably shrunken and corrugated 
and to lie at the border of the two zones. 
In a pancreas of another dog, that had 
been killed during full intestinal digestion, 
the same two zones were visible. The in- 
ner granular zone, however, was much con- 
tracted and the granules much less numer- 
ous, whereas the outer hyaline zone was 
much wider. The cell, as a whole, had 
become smaller, the nucleus had regained 
its spherical shape and was situated near 
the center of the cell. These changes in 
the cells were observed to repeat themselves 
during the several phases of digestion. In 
the same manner other observers have been 
able to demonstrate a close connection 
between the degree of granularity of the 
cell and the amount of enzyme secreted. 
In studying the secretion of diastase by 
the scutellar epithelium of germinating 
barley, Brown and Morris were able to de- 
termine that when the secretion of diastase 
had ceased the marked granularity of the 
cells had also disappeared, and, what was 
even more remarkable, the nucleus of the 
cell had disappeared also. It would seem, 
therefore, that for each enzyme there exists 
in the gland cell a distinct antecedent sub- 
stance or zymogen, ready to be transformed 
SCIENCE. 
769 
into the ferment the moment the latter is 
required. That these zymogens are not 
enzymes has been.proved by Langley, for 
pepsin at least, in the most masterly and 
convincing manner ; and the same thing has 
been shown for other zymogens by other 
equally competent observers. 
The most important histological studies 
on the formation of the zymogens have 
been made by Macallum. By employing 
nuclear stains he was able to make out that 
during the formation of the zymogen a part 
of the chromatin of the nucleus was extruded 
into the cytoplasm of the cell in the form of 
a substance which he calls prozymogen. 
On coming into the cytoplasm it unites 
with some component thereof, as the result 
of which combination the granules of 
zymogen are produced. These granules 
were observed to gradually increase in size, 
apparently at the expense of some sub- 
stance in the cytoplasmic portion of the cell. 
It will be observed that Macallum’s view 
of the formation of the zymogen granules 
enables us to understand the shrinking and 
disintegration of the nucleus during secre- 
tion. It should be borne in mind, however, 
that in the formation of the mother sub- 
stance of the ferment both nucleus and 
cytoplasm supply their quota. 
This view of the formation of the zymo- 
gens strongly supports the conclusion that 
the enzymes retain a part, at least, of 
the original activity of the living proto- 
plasm. In the formation of a new cell or 
an individual, the cell nucleus and the 
cytoplasm, of either the same or different 
cells, are involved. We have just seen, 
however, that in the production of the 
zymogen granules both the nucleus and 
cytoplasm participate. If, therefore, we 
look upon the cell nucleus as the formative 
and directive force in the one case, it would 
seem logical to so regard it in the other, 
the only difference being, that while upon 
the one hand its energies go to the forma- 
