PRESIDENTIAL ADDRESS. 657 
an oxidation product of the camphor and an oxidation product of glucose. 
Both substances were then new to chemistry, and the latter—glycuronic acid— 
has since proved itself of great physiological interest. After Schmiedeberg’s 
and Hans Meyer’s experiments it was realised for the first time that the 
sugar molecule might play a part in metabolism quite distinct from its function 
as fuel, a fact that has much of cogency at the present time. We have good 
reason to believe that though, as a matter of fact, glycuronic acid is a normal 
metabolite, the actual synthesis concerns sugar itself, the oxidation of the 
glucose molecule occurring later. The compound formed is of the glucoside 
type, and the analogy with the formation of glucosides in the plant is un- 
mistakable. Already the number of substances known to suffer this particular 
synthesis is legion. Almost every organic group yields an example. 
' Lastly, in illustration of a quite different type of synthesis (I can only deal 
with a few of the many known cases) we may recall the methylation which 
certain compounds undergo. The mechanism of this process, as it occurs in 
the body, is obscure, and its explanation would be of the greatest chemical 
interest. I must mention only one particular instance investigated by Acker- 
mann. When nicotinic acid is fed to animals, it is excreted as trigonellin, a 
known vegetable base. This conversion involves methylation, and is of striking 
character as an instance of the artificially induced production of a plant 
alkaloid in the animal bedy. 
The full significance of all such happenings will not be understood unless 
it be remembered that a nice adjustment of molecular structure is in many 
cases necessary to prepare the foreign substance for synthesis. Preliminary 
regulated oxidations or reductions may occur so as to secure, for example, 
the production 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 not been won systematically, and the fate of a 
multitude of other types of organic substances remains for investigation. The 
known facts have, one feels, an academic character in the view of the physio- 
logist, 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 potentialities of the tissue laboratories. 
In a brilliant address delivered befcre 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 over- 
power 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 physiologist 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 consequent vagueness of molecular structure as to make 
their reactions impossible of study by his available and accurate methods. There 
1913, UU 
