PRESIDENTIAL ADDRESS. 655 
Yet it is now known that the relation brought to light by Schtitz does hold for 
certain relative concentrations of ferment and substrate. That it had limitations 
was shown by Schiitz himself. The fact, however, involves no such shaking of 
the foundations as the abstractor thought. We quite understand now how such 
relations may obtain in enzyme-substrate systems. 
As for analytical work involving a separation of complex organic mixtures 
the biochemist of the last century was in this ahead of the pure organic chemist, 
as the development of urinary analysis if considered alone will show. 
In countless directions the ‘acquirement of exact knowledge concerning 
animal chemistry has been, as I have already claimed, continuous from Liebig’s 
days till now. I would like in a brief way to illustrate this, and if I choose 
for the purpose one aspect of things rather than another, it is because it will 
help me in a later discussion. J propose to remind you of certain of the steps 
by which we acquired knowledge concerning the synthetic powers of the animal 
body, apologising for the great familiarity of many of the facts which I shall put 
before you. 
It seems that the well-known Glasgow chemist and physician, Andrew Ure, 
was the first actually to prove, from observations made upon a patient, that 
an increased excretion of hippuric acid follows upon the administration of 
benzoic acid. Wohler had earlier fed a dog upon the latter substance, and 
decided at the time that it was excreted unchanged; but when, later, Liebig had 
made clear the distinction between the two acids, Wohler recalled the properties 
of the substance excreted by his dog, and decided that it must have been 
hippuric acid and not benzoic acid itself. Excited by the novel idea that a 
substance thus extraneously introduced might be caught up in the machinery 
of metabolism, Wohler, immediately after the publication of Dr. Ure’s state- 
ment, initiated fresh experiments in his laboratory at Gottingen, where Keller, 
by observations made upon himself, showed unequivocally that benzoic acid is, 
and can be on a large scale, converted into hippuric acid in the body. Thus was 
established a fact which is now among the most familiar, but which at that time 
stirred the imagination of chemists and physiologists not a little. The dis- 
covery immediately led to a large number of observations dealing with various 
conditions which affect the synthesis, but we may pass to the acute observations 
of Bertagnini. This investigator wished to earmark, as it were, the benzoic 
acid administered to the animal, in order to make sure that it was the same 
molecule which reappeared in combination. He so marked it with a nitro- 
group, giving nitro-benzoic acid and observing the excretion of nitro-hippuric 
acid. Later on he continued this interesting line of research by giving other 
substituted benzoic acids, and showed that in each case a corresponding substi- 
tuted hippuric acid was formed. Even so far back as the earlier ’fifties a clear 
understanding was thus established that the body was possessed of a special 
mechanism capable of bringing a particular class of substances into contact with 
the amino-acid glycine, and of converting them, by means of a synthetical 
condensation (which had not then been induced by any laboratory method), into 
conjugates which, as later experiments have shown, are invariably less noxious 
for the tissues than the substances introduced. Great is the number of com- - 
pounds which are now known to suffer this fate. To the story begun by Ure 
and Wohler, chapter after chapter has been added continuously up to the 
present day. In 1876 came the classical experiments of Bunge and Schmiede- 
berg. After laborious but successful efforts to obtain a good method for the 
estimation of hippuric acid in animal fluids, these authors proved, by a method 
of exclusion, that, in the dog at least, the kidney is the seat of the hippuric 
synthesis. When, in their carefully controlled experiments, blood containing 
benzoic acid and glycine was circulated through that organ, after its isolation 
from the body, the production of hippuric acid followed. Schmiedeberg, a 
little later, convinced himself that the reaction in the kidney was a balanced 
one; the organ can not only synthesise hippuric acid, it can also hydrolise it. 
As with reactions elsewhere, so in the kidney cell, the equilibrium of the 
reaction depends on the relative concentration of the products concerned. 
Schmiedeberg then separated from the tissues of the kidney what he believed to 
be an enzyme capable of inducing the hydrolysis. Mutch, with improved 
methods, has recently shown that a preparation from the kidney, wholly free 
from intact cells, can, beyond all doubt, hydrolise hippuric acid under rigidly 
