2
perfusing its blood vessels with Locke's solution containing
glucose-removes sugar from the perfusion fluid inuch more
rapidly wlhen the fluid used liad first of all been perfused
tlhrough the blood vessels of the pancreas than from fresh
Locke's solution. In tlhe liglht of these researclhes tle mnajority
of investigators concluded that a pancreatic hormone rnust
exist, but that it was impossible to detect its presence in
pancreatic extracts because of its destruction by the trypsin
and other proteolytic enzymes also present in them.
Starting-point of the Recent Advance.
The problem tlherefore was to circumvent tlhese enzymes,
and to D)r. F. G. Banting is due tlhe credit of suggesting tlhat
this might be accomplished by taking advantage of the well-
known fact that tlhe cells which secrete the digestive enzymes
beconme completely degenerated in some weeks after ligation
of tlie pancreatic ducte, wlereas those of the isles of Langer-
hans, which apparently secrete the antidiabetic hormone,
remain more or less intact. He undertook to see wlhether
extracts of tle degenerated gland iniglit yieldl rnore certain
results, and facilities asd assistance were afforded lhim in moy
department to put this suggestion to tlie test of experiment.
In collaboration witlh (J. H1. Best, Banting observed tlhe effects
produced by injection of tlhe extracts on the percentage
of sugar in the blood, as well as on the total sugar excretion
in tlhe 24-hour urine of dogs, rendered diabetic by extirpation
of tihe pancreas.5 From practically the very start of the
observations a definite lowering of both of these values was
observed to occur. lhle observations were frequently repeated
witlh all necessary controls, and it was furtlher noted that the
exhibition of tlhe extract also greatly improved tlhe subjective
condition of the animal and markedly prolonged its life. An
untreated depancreatized dog seldom lives beyond three
weeks-or four at the outside-whereas with the extracts
one such animal lived in excellent condition for ten weeks,
wlhen it was killed by clloroform. No trace of pancreas
could be seen by the naked eye post morteon, though a
very small nodule of zymogenous cells was found in the
walls of the duodenum in a careful microscopical examination.
First Therapeutic Application.
Having shown by tlhese experiments that the pancreas does
contain an antidiabetic lhorrnooe thie next step was to find
a method by wlhich an extract containing i could be made
from undegenerated gland. Knowing that proteolytic enzymes
are ailrnost, if not entirely, absent in tlhe foetal pancreas
(Ibralhim), Banting and Best° prepared extracts from this
source, and, finding tlhen also to contain the antidiabetic
hormone, tlhen proceeded to try whether an active extract
could be prepared from the pancreas of the full-grown ox, by
using alcohol as the extracting medium so as to circumvent
the destructive action of trypsin, as lhad previouslv been
suggested by E. L. Scott. Satisfactory results were obtained,
and it was considered that tlhe time had now arrived to
warrant tlhe administration of the extract to a diabetic patient.