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The author is chief resident in
Internal Medicine at the Yale
Primary Care Residency Program.
From its advent in September
2006 until its removal from the
market in October 2007, inhaled
insulin for diabetes mellitus
represented the first effective alternative
to subcutaneous injections in
more than eighty years. Aside from
its administration modality, Exubera
(Insulin Human [rDNA origin]) also
transformed dosage labeling from
the traditional insulin “unit” into
milligrams. While this conversion
may have appeared novel, it actually
harked back to a time early in insulin
therapy’s history. Indeed, defining insulin
quantity in terms of milligrams
sits at the heart of post-World War I
efforts to ensure the new product’s
safety and reliability. These early attempts
at its international standardization
laid the foundation on which
insulin dosage is still based today.
Frederick Grant Banting.
Courtesy of the National Library of Medicine.
Producing an insulin extract
In the autumn of 1920, Canadian
surgeon Frederick Grant Banting
scribbled,
Diabetus
Ligate pancreatic ducts of
dog. Keep dogs alive till acini
degenerate leaving Islets.
Try to isolate the internal secretion
of these to relieve glycosurea
[sugar in the urine]. 1p50
In this short note, Banting
outlined how he would
find the quintessentialtreatment
for a disease he could not even spell.
Over the next year, Banting worked
in the University of Toronto physiology
laboratory of Professor J. J. R.
Macleod. With the help of graduate
students Charles Best and Clark
Noble, he purified his first insulin extract
from the degenerating pancreases
of canine subjects and showed it
could transiently reduce the animals’
blood sugar.
Banting presented his findings to
the American Physiological Society
conference in December 1921. Among
attendees expressing interest in extract
production was George H. A.
Clowes, research director for the Eli
Lilly Pharmaceutical Company of
Indianapolis. Though his offer was
initially turned down, it caused the
researchers to patent their process
to maintain their control over the
integrity of the extract’s manufacture
and purification. The University of
Toronto’s Board of Governors subsequently
licensed the process to Lilly’s
laboratories. 1 American production
supplemented the relatively meager
yields at Toronto’s own Connaught
Antitoxin Laboratories, supplying
a burgeoning international market
with insulin therapy.
To oversee insulin’s future licensing
and distribution, the Board
of Governors organized Toronto’s
Insulin Committee (IC) in 1922. One
of its first actions was to offer patent
rights to the British Medical Research
Council (MRC), thus giving Europe
its first access to insulin. The MRC
sent Dr. Henry H. Dale, a department
director at their National
Institute for Medical Research, to
Toronto. Dale quickly recognized the
promise of insulin and suggested the
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