PRESIDENTIAL ADDRESS. 665 
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 nomenclature, as between organised and unorganised ‘ ferments’) : 
“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 hypo- 
thesis 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 ‘the 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 which 
some act upon only one type of polypeptide, and some specifically on other 
polypeptides. We must remember the intracellular enzymes that split the 
phosphorous 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 constitution, 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 metabolism 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 physiological significance, that this oxidase, 
though always present in the tissues of animals, which excrete allantoin, 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 accumulate 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 
