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NATURE 
[OcToBER 16, 1913 
which some act upon only one type of polypeptide, and 
some specifically on other polypeptides. We must 
remember the intracellular enzymes that slit the phos- 
phorous complexes of the cell; the lipases, the 
amylases, and the highly specific invert ferments, each 
adjusted to the hydrolysis of a particular sugar. We 
have also to think of a large group of enzymes acting 
specifically upon other substances of simple constitu- 
tion, such as the arginase of Kossel and Dakin, 
the enzyme recently described by Dakin which 
acts with great potency in converting pyruvic 
aldehyde into lactic acid, and many _ others. 
Nothing could produce a firmer belief in the reality 
and importance of the specialised enzymes of the 
tissues than a personal repetition of the experiments 
of Walter Jones, Schittenhelm, Wiechowski, and 
others, upon the agents involved in the breakdown of 
nucleic acids; each step in the elaborate process 
involves a separate catalyst. In this region of meta- 
bolism alone a small army of independent enzymes is 
known to play a part, each individual being of proven 
_ Specificity. The final stages of the process involve 
oxidations which stop short at the stage of uric acid 
in man, but proceed to that of allantoin in most 
animals. It is very instructive to observe the clean, 
complete oxidation of uric acid to allantoin, which can 
be induced in vitro under the influence of Wiechowski’s 
preparations of the uric acid oxidase, especially if 
one recalls at the same time, in proof of its physio- 
logical significance, that this oxidase, though always 
present in the tissues of animals, which excrete allan- 
toin, is absent from those of man, who does not. 
I will not trouble you with further examples. We 
have arrived, indeed, at a stage when, with a huge 
* array of examples before us, it is logical to conclude 
that all metabolic tissue reactions are catalysed by 
enzymes, and, knowing the general properties of these, 
we have every right to conclude that all reactions may 
be so catalysed in the synthetic as well as in the 
opposite sense. If we are astonished at the vast 
array of specific catalysts which must be present in 
the tissues, there are other facts which increase the 
complexity of things. Evidence continues to accu- 
mulate from the biological side to show that, as a 
matter of fact, the living cell can acquire de novo as 
the result of special stimulation new catalytic agents 
previously foreign to its organisation. 
It is certain, from very numerous studies made upon 
the lower organisms, and especially upon bacteria, 
that the cell may acquire new chemical powers when 
made to depend upon an unaccustomed nutritive 
medium. I must be content to quote a single in- 
stance out of many. Twort has shown that certain 
bacteria of the Coli-typhosus group can be trained to 
split sugars and alcohols which originally they could 
not split at all. A strain of B. typhosus which after 
being grown upon a medium containing dulcite had 
acquired the power of splitting this substance, re- 
tained it permanently, even after passage through the 
body of the guinea-pig, and cultivation upon a dulcite- 
free medium. Similar observations have been made 
upon the Continent by Massini and Burri; the latter 
showed by ingenious experiments that all the indi- 
viduals of a race which acquires such a new property 
have the same potency for acquiring it. No one, at 
the present time, will deny that the appearance of a 
new enzyme is involved in this adjustment of the cell 
to a new nutritive medium. 
We have not, it is true, so much evidence for 
similar phenomena in the case of the higher animals. 
The milk-sugar splitting ferment may be absent from 
the gut epithelium before birth, and in some animals 
may disappear again after the period of suckling, but 
here we probably have to do with some simple alterna- 
NO. 2294, VOL. 92] 
‘dress to 
tion of latency and activisation. But among the 
“protective ferments studied by Abderholden we 
have, perhaps, cases in which specific individuals 
appear de novo as the result of injecting foreig 
proteins, &c., into the circulation. Consider, more 
over, the case of the reactions called out by simpler 
substances. We have seen that an enzyme separable 
from the kidney tissue can catalyse the synthesis no 
less than the breakdown of hippuric acid. Now the 
cells of the mammalian kidney have always had to 
deal with benzoic acid or chemical precursors of 
benzoic acid, and the presence of a specific enzyme 
related to it is not surprising. But living cells are 
not likely to have ever been in contact with, say, © 
bromo-benzol, until the substance was administered to 
animals experimentally. Yet a definite reaction at 
once proceeds when that substance is introduced into 
the body. It is linked up, as we have seen, with 
cystein. Now, this reaction is not one which would 
proceed in the body uncatalysed; if it be catalysed by 
an enzyme, all that we know about the specificity 
of such agents would suggest that a new one must 
appear for the purpose. I have allowed myself to go 
beyond ascertained facts in dealing with this last 
point. But once we have granted that specific 
enzymes are real agents in the cell, controlling a 
great number of reactions, I can see no logical reason 
for supposing that a different class of mechanism 
can be concerned with any particular reaction. 
If we are entitled to conceive of so large a part of 
the chemical dynamics of the cell as comprising 
simple metaplasmic reactions catalysed by independent 
specific enzymes, it is certain that our pure chemical — 
studies of the happenings in tissue extracts, expressed — 
cell juices, and the like, gain enormously in meaning 
and significance. We make a real step forward when — 
we escape from the vagueness which attaches to the — 
“‘bioplasmic molecule’? considered as the seat of all 
change. But I am not so foolish as to urge that the — 
step is one towards obvious simplicity in our views — 
concerning the cell. For what indeed are we te 
think of a chemical system in which so great an array 
of distinct catalysing agents is present or potentially 
present; a system, I would add, which when dis- 
turbed by the entry of a foreign substance regains its 
equilibrium through the agency of new-born catalysts 
adjusted to entirely new reactions? Here seems 
justification enough for the. vitalistic view that events 
in the living cell are determined by final as well as 
by proximate causes, that its constitution has refer- 
ence to the future as well as the past. But how can 
we conceive that any event called forth in any system 
by the entry of a simple molecule, an event related 
qualitatively to the structure of that molecule, can be of 
other than a chemical nature? The very complexity, 
therefore, which is apparent in the catalytic pheno- 
mena of the cell to my mind indicates that we must 
have here a case of what Henri Poincaré has called 
la simplicité cachée. Underlying the extreme com- 
plexity we may discover a simplicity which now 
escapes us. If so, I have of course no idea along 
what lines we are to reach the discovery of that sim- 
plicity, but I am sure the subject should attract the 
contemplative chemist, and especially him who is in- — 
terested and versed in the dynamical side of his sub- 
ject. If he can arrive at any hypothesis sufficiently 
general to direct research he will have opened a new 
chapter of organic chemistry—almost will he have 4 
created a new chemistry. 
It must not be supposed that I am blind to the fact 
that the phenomena of the cell present a side to 
which the considerations I have put before you do not 
apply. Paul Ehrlich, in his recent illuminating ad- 
the International Congress of Medicine, 
et Aisa Sen 
