OcTOBER 16, 1913] 
esis. Preliminary regulated oxidations or reduc- 
tions may occur so as to secure, for example, the 
roduction of an alcoholic or phenolic hydroxyl group, 
which then gives the opportunity for condensation 
which was otherwise absent. 
I have touched only on the fringes of this domain. 
The body of knowledge available concerning it has 
tude of other types of organic substances remains for 
investigation. The known facts have, one feels, an 
academic character in the view of the physiologist, 
and even in that of the pharmacologist, to whom we 
owe most of our knowledge about them. But, in my 
opinion, the chemical response of the tissues to the 
chemical stimulus of foreign substances of simple 
constitution is of profound biological significance. 
Apart from its biological bearings as the simplest type 
of immunity reaction, it throws vivid light, and its 
further study must throw fresh light on the poten- 
tialities of the tissue laboratories. 
In a brilliant address delivered before the faculty 
_of medicine of the University of Leeds, Lord Moulton 
likened the process of recovery in the tissues after 
bacterial invasion to the generation of forces which 
establish what is known to the naval architect as the 
“righting couple.’ This grows greater the greater 
the displacement of a ship, and finally may become 
sufficient to overpower the forces tending to make 
her heel over. It is surely striking to realise that 
the establishment of the ‘righting couple’? which 
brings the tissue cell back to equilibrium after the 
_ disturbances due to the intrusion of simple molecules 
calls for such a complex of chemical events, events 
which ultimately result in the modification of the 
disturbing substance and its extrusion from _ the 
_ tissues concerned in a form less noxious to the body 
as a whole. 
Oxidation, reduction, desaturation, alkylation, 
acylation, condensation; any or all of these processes 
may be brought de novo into play as the result of the 
intrusion of a new molecule into reactions which were 
in dynamic equilibrium. It is clear that chemical 
systems capable of so responding to what may be 
termed specific chemical stimuli must not be neglected 
by any student of chemical dynamics. The physio- 
logist has for many years been engaged upon careful 
analyses of the mechanical and electric responses to 
stimulation. In the phenomena before us we find 
“responses’’ which are. equally fundamental. If we 
do not study them exhaustively we shall miss an 
important opportunity for throwing light upon the 
nature of animal tissues as chemical systems. 
One reason which has led the organic chemist to 
avert his mind from the problems of biochemistry is 
the obsession that the really significant happenings 
in the animal body are concerned in the main with 
substances of such high molecular weight and conse- 
quent vagueness of molecular structure as to make 
their reactions impossible of study by his available 
and accurate methods. There remains, I find, pretty 
widely spread, the feeling—due to earlier biological 
teaching—that, apart from substances which are 
obviously excreta, all the simpler products which can 
be found in cells or tissues are as a class mere dejecta, 
already too remote from the fundamental biochemical 
events to have much significance. So far from this 
being the case, recent progress points in the clearest 
way to the fact that the molecules with which a most 
important and_ significant part > of the chemical 
dynamics of living tissues is concerned, are of a 
comparatively simple character. The synthetic re- 
actions which we have already considered surely pre- 
pare us for this view; but it may be felt that, however 
important, they represent abnormal events, while the 
not been won systematically, and the fate of a multi- | 
NATURE 
217 
ing the end-products of change. Let me now turn 
to normal metabolic processes and to intermediary 
reactions. 
We know first of all that the raw material of 
metabolism is so prepared as to secure that it shall 
be in the form of substances of small molecular 
weight; that the chief significance of digestion, in- 
deed, lies in the fact that it protects the body from 
complexes foreign to itself. Abderhalden has ably 
summarised the evidence for this and has shown us 
also that, so far as the known constituents of our 
dietaries are concerned, the body is able to maintain 
itself when these are supplied to it wholly broken 
down into simple bausteine, any one of which could be 
artificially synthesised with the aid of our present 
knowledge. Dealing especially with the proteins, we 
have good reason to believe that the individual con- 
stituent amino-acids, and not elaborate complexes of 
these, leave the digestive tract, while Folin, Van 
Slyke, and Abel have recently supplied us with sug- 
gestive evidence for the fact that the individual amino- 
acids reach the tissues as such and there undergo 
change. 
But still more important, when things are viewed 
from my present point of view, is the fact 
that recent work gives clear promise that we shall 
ultimately be able to follow, on definite chemical lines, 
the fate in metabolism of each amino-acid individu- 
ally; to trace each phase in the series of reactions 
which are concerned in the gradual breakdown and 
oxidation of its molecule. Apart from the success 
to which it has already attained, the mere fact that 
the effort to do this has been made is significant. To 
those at least who are familiar with the average 
physiological thought of thirty years ago, it will 
appear significant enough. So long as there were 
any remains of the instinctive belief that the carbonic 
acid and urea which leave the body originate from 
oxidations occurring wholly in the vague complex of 
protoplasm, or at least that any intermediate products 
between the complex and the final excreta could only 
be looked for in the few substances that accumulate 
in considerable amount in the tissues (for instance, 
the creatin of muscle), the idea of seriously trying 
to trace within the body a series of processes which 
begin with such simple substances as tryosin or 
leucin was as foreign to thought as was any con- 
ception that such processes could be of fundamental 
importance in metabolism. However vaguely held, 
such beliefs lasted long after there was justification 
for them; their belated survival was due, it seems 
to me, to a certain laziness exhibited by physiological 
thought when it trenched on matters chemical; they 
disappeared only when those accustomed to think in 
terms of molecular structure turned their attention to 
the subject. But it should be clearly understood that 
the progress made in these matters could only have 
come through the work and thought of those who 
combined with chemical knowledge trained instinct 
and feeling for biological possibilities. Our present 
knowledge of the fate of amino-acids, as of that of 
other substances in the body, has only been arrived 
at by the combination of many ingenious methods of 
study. 
It is easy in the animal, as in the laboratory, 
to determine the end-products of change; but, when 
the end result is reached in stages, it is by no means 
easy to determine what are the stages, since the 
intermediate products may elude us. And yet the 
whole significance of the processes concerned is to be 
sought in the succession of these stages. In animal 
experiments directed to the end under consideration, 
investigators have relied first of all upon the fact 
that the body, though the seat of a myriad reactions, 
study of them has been largely confined to determin- ! and capable perhaps of learning, to a limited extent 
NO. 2294, VOL. 92] 
