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From rabbits to the League of Nations
MRC accept control of the British patent.
At the same time, he and his traveling
companion, biochemist Harold W.
Dudley, expressed serious reservations
regarding the IC’s earliest definition of
the insulin unit. Dale wrote:
The Toronto definition of a “unit”
of the specific insulin activity, was
the dose required, with intravenous
injection, to throw 3 out of 5 rabbits
into hypoglycaemic convulsions! I
had made it no secret, from the first,
. . . that I regarded such a definition
as having so little claim to accuracy,
as to be practically almost useless,
and eventually misleading. 2p445
Clowes from Lilly later echoed these
misgivings when developing a reliable
insulin unit became a matter of international
concern.
A rabbit-based unit
Dale’s observation came months after
the first insulin unit was defined.
During the spring of 1922, Macleod,
James B. Collip, Banting, and Best began
calibrating insulin by its effects on animals.
Using two-kilogram rabbits, they
determined that hypoglycemic convusions
usually appeared as the animals’
blood sugar component fell below 0.045
percent. This observation served as a
threshold on which to base the first
“physiologic unit” or “rabbit unit” of insulin,
about one cc. The authors wrote:
As a tentative basis for the physiological
assay of insulin we consider
as one unit the number of
cubic centimeters which causes the
blood sugar of normal rabbits to fall
to 0.045 per cent within 4 hours.
This dose is decidedly active in lowering
the blood sugar in diabetic
patients. 3p175
Their report also compared the effects
of infused insulin solution on a
two-kilogram normal rabbit with an
eleven-kilogram depancreatized dog.
The authors noted that, after taking
into account the animals’ weight and
dosage disparities, the dog still showed a
much more dramatic reduction in blood
sugar levels after having received only
one third the dose that the rabbit had
received. 3 The unit’s value would change
later that year to reflect this observation.
These early attempts to define an
insulin unit coincided with the first
diabetic human patients being treated
with the pancreatic extract. Fifteenyear-old
Elizabeth Hughes, the diabetic
daughter of New York governor
and future Chief Justice Charles Evans
Hughes, began her injections in mid-
August. Just one cc twice daily effectively
cleared the sugar from her urine.
However, by October her dosage had
risen to five cc twice daily. In a letter to
her mother, Hughes wrote:
Courtesy of the National Library of Medicine.
30 The Pharos/Winter 2011