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Charles H. Best.
Courtesy of the National Library of Medicine.
We only have a two cc. syringe you
know and so Blanche [her nurse]
fills that and gives it to me and then
unscrews it from the needle which
is left sticking in to me (I feel like a
pincushion) fills it again, and gives
me that (am left a pincushion once
more), and then have the fifth cc.
It really is quite a process, and altogether
takes about twenty minutes
for the whole performance. 1p155
There is no indication that Elizabeth
Hughes’s diabetes had worsened, nor
that her sensitivity to insulin had decreased.
Since she remained in Toronto
for the first months of treatment, it is
almost certain she received her insulin
from the same source, Connaught
Antitoxin Laboratories. A lack of consistency
in production protocol and
continued efforts to increase their yield
resulted in wide fluctuation
in the final product’s
activity. Therefore, while
Canadian researchers held
the definition of an insulin
unit constant in terms of
its clinical effects on rabbits,
the actual dosage fluctuated
greatly. 1
An ever-evolving unit
Late in 1922, additional
criticism of the definition
of the insulin unit emerged
from giants in American
diabetology such as Dr.
Frederik Madison Allen
and Dr. Elliot P. Joslin.
These physicians and their
colleagues disliked the
“physiologic unit” of insulin
because its relative
strength in humans forced
some patients to receive
fractions of a unit, creating
confusion among patients
and nurses alike. 4 Clowes
at Lilly brought their
concerns to the IC. On
December 30, 1922, they
announced:
The Toronto Committee conferred
with Drs Clowes, Allen and Joslin as
to the adoption of a unit for Insulin
required to lower the blood sugar
and the following conclusions were
arrived at:
1) The unit adopted for Insulin
shall be approximately one-fifth that
of the original Toronto unit, which
is the amount of Insulin required to
lower the blood sugar of a 2 kg fed
rabbit 0.045 per cent within four
hours, and cause symptoms. 4
This new unit was to be called the “clinical
unit” of insulin as opposed to the
original “physiological,” “Toronto,” or
“rabbit” unit. In this manner, the IC
had adjusted its calibration of insulin to
accommodate the needs of clinicians,
as represented by Lilly. Further col-
laborations between the pharmaceutical
company and the IC would not proceed
as smoothly.
As with Elizabeth Hughes’s insulin
supply, clinicians in 1923 complained of
potency discrepancies among batches
supposedly of the same clinical strength.
California physician W. D. Sansum and
his research team provided unique insight
into the unit’s evanescence. During
early 1923, they helped establish the
“sugar-metabolizing power” of a given
lot of insulin—the amount of sugar metabolized
by each insulin unit. They
showed Lilly’s insulin to have 1.25 grams
of sugar metabolizing power per unit. 5
Unfortunately, clinicians and their patients
remained vulnerable to continued
unit modifications elsewhere.
Beginning in May, the researchers
noted that previously well-controlled
diabetic patients had sugar reappearing
in their urine. The new insulin
units’ sugar metabolizing power had
decreased by approximately one third
compared to one month previously. The
authors state:
We then learned that the unit had
been redefined as being one-third
of the amount required to lower
the blood sugar below 0.045% and
cause convulsions in a two-kilogram
rabbit which had been previously
starved for twenty-four hours. This
redefinition was based on the belief,
supported by experimental evidence,
that it requires four times as
much insulin to cause a convulsion
in a two kilogram rabbit as in a
one kilogram rabbit. In using onethird
instead of one-fourth the convulsion
[dose] in the two kilogram
rabbits, these workers believed that
they were increasing the value of
the unit. 5
Their comments allude to discrepancies
in rabbit size between Lilly’s laboratories
and those of the IC. While Toronto
had been using two-kilogram fed rabbits
in its tests of potency, Lilly had
been using one-kilogram fasting rabbits.
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