188 
NATURE 
[FEBRUARY 10, 1923 

Insulin, Diabetes, and Rewards for Discoveries. 
By Sir W. M. Bavutss, F.R.S. 
A NUMBER of problems, some of great scientific 
interest, others of practical importance in 
various ways, have been brought to notice by the 
somewhat sensational statements in the daily press 
relating to the Canadian treatment of diabetes by a 
preparation extracted from the pancreas and known 
as “insulin” (see NaTuRE, November 25, p. 713; 
December 9, p. 774). In order to understand the state 
of affairs, it is necessary to review briefly our present 
knowledge of the physiological processes concerned 
with the utilisation of carbohydrate food. This will 
also serve to direct attention to gaps which need filling 
up, and the opportunities afforded by a trustworthy 
preparation of the hormone of the pancreatic “ islets.” 
If such a preparation shows itself to be of value in 
the treatment of diabetes in man, it is clear that 
difficulties of several kinds arise in the ensuring of an 
adequate commercial supply of an active product. 
We shall see further that the question of due rewards 
for discoveries which involve the cure of disease arises 
in the present case in an acute form. 
If we look at tables drawn up to indicate a reasonable 
proportion between the constituents of a normal diet, we 
notice how large a part of the total energy required is 
supplied by carbohydrate. In that of the Royal 
Society Food Committee, for example, more than 
65 per cent. is from this source. The justification is 
given by the fact that evidence of various kinds shows 
that the material from which muscle directly derives 
the energy for its activity in normal conditions is 
glucose. This is burned up with consumption of 
oxygen, while the products finally leave the body as 
carbon dioxide and water. Since measurements of 
the “ Respiratory Quotient ” in muscular work form 
a part of the evidence and are of importance in judging 
the properties of insulin, a word may be useful here as 
to the meaning of this number. If glucose is burned 
in the ordinary way in air, and the amount of oxygen 
consumed and of carbon dioxide and water produced is 
determined, the volume of carbon dioxide is found to 
be equal to that of the oxygen used. This is of course 
due to the fact that carbohydrate contains sufficient 
oxygen in its molecule to oxidise the hydrogen. Fat or 
protein, on the other hand, requires more oxygen, to 
burn part of the hydrogen as well as the carbon. The 
respiratory quotient expresses the ratio of the volume 
of the carbon dioxide produced to that of the oxygen 
consumed, so that if carbohydrate alone is burned, the 
value is unity, and it decreases in proportion to the 
amount of the fat or protein burned. [If it rises, due 
attention being paid to absence of retention of carbon 
dioxide, we are justified in concluding that more 
carbohydrate is being oxidised. 
Glucose is also known to be consumed in other 
organs—the secreting glands, for example—and prob- 
ably in the tissues generally. It is supplied by the 
blood, although only present therein in very low 
concentration, about o-1 to o-15 per cent. Being a 
crystalloid and filtering through the glomeruli of the 
kidney, a large quantity would be lost were it not that 
as this filtrate flows along the renal tubules, the glucose 
is almost entirely reabsorbed, along with other con- | 
NO. 2780, VOL. I11] 
stituents of value. If, however, the concentration 
of sugar in the blood rises aboye the normal value 
(hyperglycemia), owing to a large amount of carbo- 
hydrate in the food, or an incapacity on the part of 
the tissues to consume it to the proper degree, then the 
absorptive power of the kidney is insufficient, and 
sugar appears in the urine (glycosuria). The glyco- 
suria resulting from excess of blood-sugar owing to 
diet is in itself harmless; glucose is often added to 
gum-saline for intravenous injection in cases of trau- 
matic shock. When glycosuria, on the other hand, is 
due to failure to consume glucose, we have the morbid 
state known as diabetes mellitus, in which there are 
involved other consequences of this defect, themselves 
giving rise to serious symptoms. ; 
Since the supply of sugar from the digestive canal is 
intermittent and in excess of the immediate demand, 
while this demand is constant, it is clear that some 
means of storage is needed. This is provided by the 
liver, which deposits glucose in its cells in the form of 
the insoluble glycogen. From this store it is released 
as required. The muscular tissues, especially that 
of the heart, are also able to store glycogen to some 
extent. Now in diabetes it is found that the liver has 
lost this power, although the muscles retain it. It is 
not obvious why this loss of storage power in the liver 
should be connected with failure of the tissues generally 
to consume glucose, but so it is; and there is another 
rather remarkable fact. If the food given to a diabetic 
animal is devoid of carbohydrate, glucose is produced 
from certain amino-acid components of proteins, 
although it is not utilised, and escapes in the urine. 
It may be that the consumption of glucose is never 
completely absent in diabetes, but is dependent on a 
high concentration in the blood. This minimal con- 
sumption being absolutely essential to life, it is provided 
from protein, if no other supply is available. Hence 
the great wasting of body substance present in diabetes. 
In the year 1889, a paper by Von Mering and Min- 
kovski was published, in which it was-shown that if 
the pancreas was removed from dogs, a condition like 
that of diabetes was produced. They found further 
that if a small piece of the pancreas had previously 
been grafted under the skin, removal of the rest of 
the pancreas was ineffective until this graft was also 
removed. It was also found that ligature of the ducts 
of the pancreas did not produce diabetes. These 
results pointed clearly to an internal secretion from the 
pancreas as being necessary for the utilisation of sugar. 
It was found that the residue of pancreatic tissue left 
in both the cases referred to consisted of the structures 
known as “ Islets of Langerhans,” and it was advocated 
by Sharpey Schafer that these organs are responsible 
for the internal secretion. Further evidence confirmed 
this view, although there are still some differences of 
opinion as to the independence of the islet tissue and 
the ordinary secreting tissues. The discovery of 
Diamare that in many teleostean fishes the islet 
tissue exists in organs separate from the pancreas is — 
important evidence that this tissue is not in the adult 
formed from the pancreatic cells. In Lophius, accord- 
ing to Diamare, these masses of islet tissue may be as 
