100 AMERICAN DIABETES ASSOCIATION
familiar with the variations to be expected in diabetics
under treatment. We were fortunate then to be constantly
in touch with the physiological observations as they pro-
gressed. It is true though that the injection of pancreatic
extract did produce a small reduction in blood sugar and
in glycosuria, and provided some encouragement to con-
tinue. More concentrated extracts were provided and these
yielded better results, but many delays and disappoint-
ments were still in store until a standardized process could
be worked out. For example: Collip put a batch of potent
extract through a Berkefeld filter and it entirely lost
potency. This was controlled by suitable adjustnment of the
hydrogen ion concentration of the solution but, even when
a process was shown to be effective in five-litre lots, the
transfer of the process to a semi-manufacturing scale was
impossible and new conditions had to be worked out.
As supplies permitted, the work was continued and
commenced to yield more satisfying results. In March,
1922, a preliminary report2 was published reviewing briefly
the physiological background and relating the progress
made in the clinical field. It was stated that: "Blood sugar
can be markedly reduced even to the normal values. Gly-
cosuria can be abolished. The acetone bodies can be made
to disappear from the urine. The respiratory quotient
shows evidence of increased utilization of carbohydrates.
A definite improvement is observed in the general condi-
tion of these patients and in addition the patients them-
selves report a subjective sense of well being and increased
vigor for a period following the administration of these
preparations."
Among the tragedies of this early period was a little
friend of Best from a nearby suburb, who came to hospital
in acidosis and Who was rescued from near-coma several
times during the next few weeks. Collip gave us the last
bit of partially completed extract at two o'clock one morn-
ing and then no more could be completed for days. It was
not enough. Though a failure, this patient taught us
much. As you know, the death of diabetic dogs cannot
strictly be compared to the phenomena of acidosis and
coma in human beings, so this was an experience not cov-
ered hy physiological investigations. We saw the improve-
ment after administration of pancreatic extract and the