changes. 
the microscope, and the phenomena would be just as 
significant it reactions occur in the water imbibed by 
spaces of the bioplasm. 
actual 
OcToBER 16, 1913] 
tive processes also occur outside them. We need not 
think of a visible vacuole as the only seat of such 
Similar fluid phases in the cell may elude 
the colloids of the cell or present in the intra-micellar 
It is always important to 
remember that 75 per cent. of the cell substance 
consists of water. 
All of these considerations we may apply to the 
tissue cells of the higher animal. To my mind, at 
least, the following considerations appeal. It is note- 
worthy that all the known complexes of the cell— 
the proteins, the phosphorous complexes, the nucleic 
acids, &c.—are susceptible to hydrolysis by catalytic 
agents, which are always present, or potentially 
present. If the available experimental evidence be 
honestly appraised, it points to the conclusion that 
only to hydrolytic processes are the complexes un- 
stable. Under, the conditions of the body they are, 
while intact, resistant to other types of change, their 
hydrolytic products being much more susceptible. 
Since hydroclastic agents are present in the cell we 
must suppose that there is, at any moment, equili- 
brium between the complexes and their water-soluble 
hydrolytic products, though the amount of the latter 
present at any moment may be very small. Now, I 
think we are entitled to look upon assimilation and 
dissimilation, while very strictly defined, as being 
dependent upon changes in this equilibrium alone. 
They are processes of condensation and hydrolysis 
respectively. Substances which are foreign to the 
normal constitution of the complexes—and these com- 
prise not only strictly extraneous substances, but 
material for assimilation not yet ready for direct con- 
densation, or metabolites which are no longer simple 
hydrolytic products—do not enter or re-enter the com- 
plexes. They suffer change within the cell, but not 
as part of the complexes. When, for instance, a 
supply of amino-acids transferred from the gut 
reaches the tissue cell, they may be in excess of the 
contemporary limits of assimilation; or, once more, 
individual acids may not be present in the har- 
monious proportion required to form the specific pro- 
teins in the cell. Are we to suppose that all never- 
theless become an integral part of the complexes 
before the harmony is by some mysterious means 
adjusted? .I think rather that the normality of the 
cell proteins is maintained by processes which precede 
condensation or assimilation. Conversely, 
when the cell balance sets towards dissimilation, the 
amino-acids liberated by hydrolysis suffer further 
changes outside the complexes. So when a foreign 
substance, say benzoic acid, enters the cell, we have 
no evidence, experimental or other, to suggest that 
such a body ever becomes an integral part of the 
complexes. Rather does it suffer its conjugation with 
glycine in the fluids of the cell. So also with cases of 
specific chemical manufacture in organs. When, for 
instance, adrenaline—a simple, definite crystalline 
body—appears in the cells of the gland which prepares 
it, are we to suppose that its molecule emerges in 
some way ready-made from the protein complexes of 
the gland, rather than that a precursor derived from 
a normal hydrolytic product of these proteins or from 
“the food supply is converted into adrenaline by re- 
actions of a comprehensible kind, occurring in aqueous 
solution, and involving simple molecules throughout ? 
While referring to adrenaline, I may comment upon 
the fact that the extraordinarily wide influence now 
attributed to that substance is a striking illustration 
of the importance of simple molecules in the dynamics 
of the body. : 
It should be, of course, understood, though the 
NO. 2294, VOL. 92] 
NATURE 
hea 
consideration does not affect the essential significance 
of the views I am advancing, that the isolation of 
reactions in particular phases of the cell is only rela- 
tive. I have before emphasised the point that the 
equilibrium of the whole system must, to a greater 
or less degree, be affected by a change in any one 
phase. A happening of any kind in the fluid phases 
must affect the chemical equilibrium and, no less, the 
physico-chemical equilibrium, between them and the 
complexes or less fluid phases. A drug may have an 
“action” on a cell, even though it remain in solution, 
and it may have a specific action because its mole- 
cular constitution leads it to intrude into, and modify 
the course of, some one, rather than any other, of the 
numerous simple chemical reactions proceeding in the 
cells of different tissues. 
But I must now turn from consideration of the re- 
actions themselves to that of their direction and con- 
trol. It is clear that a special feature of the living 
cell is the organisation of chemical events within it. 
So long as we are content to conceive of all hap- 
penings as occurring within a biogen or living mole- 
cule all directive power can be attributed in some 
vague sense to its quite special properties. 
But the last fifteen years have seen grow up a 
doctrine of a quite different sort which, while it has 
difficulties of its own, has the supreme merit of pos- 
sessing an experimental basis and of encouraging by 
its very nature further experimental work. I mean 
the conception that each chemical reaction within the 
cell is directed and controlled by a specific catalyst. 
I have already more than once implicitly assumed 
the existence of intracellular enzymes. I must now 
consider them more fully. 
Considering the preparation made for it by the 
early teaching of individual biologists, prominent 
among whom was Moritz Traube, it is remarkable 
that belief in the endo-enzyme as a universal agent 
of the cell was so slow to establish itself, though in 
the absence of abundant experimental proof scepticism 
was doubtless justified. So long as the ferments 
demonstrated as being normally attached to the cell 
were only those with hydroclastic properties, such as 
were already familiar in the case of secreted digestive 
ferments, the imagination was not stirred. Only with 
Buchner’s discovery of zymase and cell-free alcoholic 
fermentation did the faith begin to grow. Yet, a 
quarter of a century before, Hoppe-Seyler had written 
(when discussing the then vexed question of nomen- 
clature, as between organised and unorganised “ fer- 
ments”): ‘The only question to be determined is 
whether that hypothesis is too bold which assumes 
that in the organism of yeasts there is a substance 
[the italics are mine] that decomposes sugar into 
alcohol and CO, ...I hold the hypothesis to be 
necessary because fermentations are chemical events 
and must have chemical causes. .. .”” If in the last 
sentence of this quotation we substitute for the word 
“fermentations” the words ‘tthe molecular reactions 
which occur within the cell,’ Hoppe-Seyler would, I 
think, have been equally justified. 
Remembering, however, the great multiplicity of 
the reactions which occur in the animal body, and 
remembering the narrow specificity in the range of 
action of an individual enzyme, we may be tempted 
to pause on contemplating the myriad nature of the 
army of enzymes that seems called for. But before 
judging upon the matter the mind should be prepared 
by a full perusal of the experimental evidence. We 
must call to ‘mind the phenomena of autolysis and 
all the details into which they have been followed; the 
specificity of the proteolytic ferments concerned, and 
especially: the evidence obtained by Abderhalden and 
others, that tissues contain numerous enzymes, of 
