656 TRANSACTIONS OF SECTION I. 
aseptic conditions, the reaction being one which comes to an equilibrium point 
when some 97 per cent. of the substance is broken down. The occurrence of this 
equilibrium, and the form of the reaction-velocity curve as obtained by Mutch, 
suggested that synthesis under the influence of the enzyme was to be expected, 
and, on submitting the mixture of benzoic acid and glycine to its influence, Mutch 
obtained a product which, though too small in amount for analysis, was almost 
certainly hippuric acid. I have myself obtained evidence which shows that the 
synthesis does certainly occur under these conditions. 
The significance of this earliest known synthesis in the body is no limited 
one. The amide linkage established by it is one with which the body deals 
widely, and is, of course, of the type which is dominant in tissue complexes, 
since it is one which unites the amino-acids in the protein molecule. 
Seeing, from the nature of the material supplied for the synthesis by the body 
itself, that the foreign substances administered must intrude themselves into 
the machinery of protein metabolism, it is not surprising that many have turned 
their minds to consider how far a detailed study of the phenomena might throw 
light upon this machinery. How far can the body extend its supply of glycine 
when stimulated by increasing doses of benzoic acid? What effects follow when 
administration is pushed to its limits? How is the fate in metabolism of the 
whole molecule of protein affected when one particular amino-acid is inhar- 
moniously removed? Can the amino-acid be itself synthesised de novo in 
response to the call for it? These and similar questions clearly arise. I can 
only stop to remind you that there is evidence that, in connection with this 
particular chemical synthesis, the carnivore reacts differently to the herbivore. 
If the body of the former be flooded with benzoic acid, only a proportion under- 
goes condensation. Only so much glycine is supplied as would correspond, 
roughly, at any rate, with that rendered available by the normal contemporary 
breakdown of protein, whereas, in the herbivorous animal, pushing the adminis- ~ 
tration of benzoic acid may lead to the excretion of so much conjugated glycine 
that it may contain more than half of the whole nitrogen excreted. This is, of 
course, much more than could come from the protein of the body, and it would 
seem that the amino-acid is prepared de novo for an express purpose, a signifi- 
cant thing. But I must not stop to consider questions which are still in course 
of study. Before the hippuric synthesis was first observed synthetic powers 
were thought to be absent from the animal. Since then we have been con- 
tinuously learning of fresh instances of synthesis in the body, not only in 
connection with its treatment of foreign substances, with which I am just 
now concerned, but in connection with all its normal processes. 
Another most interesting group of syntheses in which substances are so 
dealt with in the body as to reappear in conjugation with protein derivatives 
are those in which the sulphur group plays its part. In 1876 Baumann first 
introduced us to the ethereal sulphates of the urine. and, from much subsequent 
work, we know how great a group of substances, chiefly those of phenolic 
character, are, after administration, excreted linked to sulphuric acid. We 
have evidence to show that, in all probability, the original condensation is not 
with sulphuric acid itself, but that oxidation of a previously formed sulphur 
containing conjugate has preceded excretion, and we know that another group 
of substances leave the body combined with unoxidised sulphur. Certain 
cyanides—the aliphatic nitriles, for example—reappear as sulpho-cyanides; but 
above all in interest is the case described by Baumann, in which the intact 
cystein complex of protein, after suffering acetylation of its amino group, 1s 
excreted as a conjugate. The administration of halogen-benzene compounds is 
followed by the appearance of the so-called mercapturic acids in which the 
cystein is linked by its sulphur atom to the ring of chlor-, bromo-, or iodi- 
benzene. That large amounts of these conjugates can be formed during the 
twenty-four hours is certain, but it would be interesting to know what limit is 
set to this loss of cystin from the body. 
I will now recall to you syntheses in which the substance supplied by the 
body is derived, not from protein, but from carbohydrate. The study of the 
fate of camphor in the body, carried out by Schmiedeberg and Hans Meyer in 
1878, if it stood by itself, would abundantly illustrate the significance of this 
type of experiment. As you are aware, these workers proved that, after the 
administration of camphor, the urine contains a conjugate formed between 
