for extraneous labours. 
OcToBER 16, 1913] 
NATURE 
215 
develop the art of analysis on these lines. Of the 
myriad substances, natural or artificial, known to 
im at the most a few score could be separated quanti- 
tatively from mixtures, or estimated with any accu- 
racy. It was a professional or commercial call rather 
than scientific need which evolved such processes as 
were available, so that this side of chemical activity 
developed only on limited and special lines. 
All these circumstances were, of course, inevitable. 
Organic chemistry in Liebig’s later years was con- 
‘cerned with laying its own foundations as a pure 
science, and for the rest of the century with building 
a giant, self-contained edifice upon them. ‘The great 
business of developing the concepts of molecular 
structure and the wonderful art of synthesis were so 
absorbing as to leave neither leisure nor inclination 
But it is easy to recognise 
that, near the beginning of the present century, a 
sense of satiety had arisen in connection with syn- 
thetic studies carried out for their own sake. Workers 
came to feel that, so far as the fundamental theo- 
retical aspects of chemistry were concerned, that par- 
ticular side of organic work had played its part. In 
numerous centres, instead of only in a few, quite 
other aspects of the science were taken up: in par- 
ticular, the study of the dynamic side of its pheno- 
mena. The historian will come to recognise that a 
considerable revolution in the chemical mind coincided 
roughly with the beginning of this century. Among 
the branches which are fated to benefit by this revolu- 
tion—it is to be hoped in this country as well as 
others—is the chemistry of the animal. 
But I would like to say that I do not find, on read- 
ing the contributions to science of those who, as pro- 
fessed physiological chemists, ploughed lonely furrows 
in the last century, any justification for the belief that 
the work done by them was amateurish or inexact; 
no suggestion that anything inherent in the subject 
is prone to lead to faults of the kind. Truly these 
workers had to share ignorance which was universal, 
and sometimes, compelled by the urgency of certain 
problems, had perforce to do their best in regions 
that were dark. But they knew their limitations here 
as well as their critics did, and relied for their justifi- 
cation upon the application of their results, which was 
often not understood at all by their critics. 
There is little doubt, for instance, that it was the 
earlier attempts of various workers to fractionate 
complex colloid mixtures that led to the cynical state- 
ment that ‘* Thierchemie is Schmierchemie.” But the 
work thus done, even such work as Kiihne’s upon 
the albumoses and peptones, had important bearings, 
and led indirectly to the acquirement of facts of great 
importance to physiology and pathology. 
-In connection with enzyme catalysis the work done 
at this time by physiological chemists was in the main 
of a pioneer character, but it was urgently called for 
and had most useful applications. By the end of the 
century, indeed, it had become of great import- 
ance. I recall an_ incident which _ illustrates 
the need of suspended judgment before work 
done in new regions is assumed to be inexact. 
In 1885 E. Schiitz published a study of the hydrolysis 
of protein by pepsin which showed that the rate of 
action of the ferment is proportionate to the square 
root of its concentration. When this paper was dealt 
with in Maly’s ‘‘Jahresbericht” the abstractor (who 
from internal evidence, I believe, was Richard Maly 
himself) believed so little in such an apparent depar- 
ture from the laws of mass action that he saw fit to 
deal with the paper in a ribald spirit, and to add, as 
a footnote to his abstract, the lines :— 
“* Musst mir meine Erde 
Doch lassen steh'n 
Und meine Hiitte die du nicht gebaut !” 
NO. 2294, VOL. 92] 
Yet it is now known that the relation brought to 
light by Schiitz does hold for certain relative concen- 
trations of ferment and substrate. That it had limita- 
tions was shown by Schiitz himself. The fact, how- 
ever, 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 until now. I would like in a brief way to illus- 
trate 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. I 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 statement, initiated 
fresh experiments in his laboratory at Géttingen, 
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 discovery immediately led to a large 
number of observations dealing with various condi- 
tions which affect the synthesis, but we may pass to 
the acute observations of Bertagnini. This investi- 
gator 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 corre- 
sponding substituted hippuric acid was formed. Even 
so far back as the earlier ‘fifties a clear understand- 
ing was thus established that the body was possessed 
of a special mechanism capable of bringing a par- 
ticular 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 conju- 
gates which, as later experiments have shown, are 
invariably less noxious for the tissues than the sub- 
stances 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 Schmiedeberg. After laborious but successful 
efforts to obtain a good method for the estimation of 
