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[IP] The Discovery of Insulin



The Discovery of Insulin
25th Anniversary Edition. By Michael Bliss. 304 pp., illustrated. Chicago,
University of Chicago Press, 2007. $22.50. ISBN: 978-0-226-05899-3 

During the past century, medical science has produced numerous remarkable
therapeutic achievements, but few accomplishments can rival - in terms of
importance or drama - the development of insulin in 1921 and 1922. The
heroic outlines of the story can be sketched briefly: Frederick Banting, a
29-year-old surgeon struggling with debt, has a flash of insight and travels
to Toronto, where he manages to convince a skeptical professor of physiology
- the esteemed J.J.R. Macleod - to provide him with laboratory support for a
few months during the summer of 1921. For a month, Macleod helps Banting get
up and running, then travels to Scotland. Banting is assisted by an honors
undergraduate student, Charles Best, in a series of experiments with dogs
that have undergone surgical removal of the pancreas, some of which yield
astonishing results. When Macleod returns and the previous tantalizing
results cannot be reliably replicated, the biochemist J.B. Collip joins the
effort, devising a different way to obtain the pancreatic extract during
December of 1921. In January 1922, the crude insulin extract is first
injected into a patient with diabetes; the result is only a mild lowering of
blood sugar (and the development of sterile abscesses, which were a common
complication of the early extracts). Forging ahead despite setbacks, by the
beginning of 1923 both Eli Lilly and Company in the United States and
Connaught Laboratories in Canada start industrial production of insulin,
transforming the lives of all persons living with what we now call type 1
diabetes. The all-too-human and at times almost tragic contours of this
narrative are marred by tempestuous arguments among the protagonists that
swell into an epic internecine squabble over credit for the discovery. The
argument erupts into public controversy when, in 1923, Banting and Macleod
(but neither Collip nor Best) are awarded the Nobel Prize in Physiology or
Medicine.

 <http://www.nejm.org/action/showImage?doi=10.1056%2FNEJMbkrev58827&iid=f01>
http://www.nejm.org/na102/home/ACS/publisher/mms/journals/content/nejm/2008/
nejm_2008.358.issue-9/nejmbkrev58827/production/images/small/nejmbkrev58827_
f1.gifPhotographs of a Young Female Patient of Dr. H. Rawle Geyelin, before
and after Treatment with Insulin, 1922. 

Twenty-five years ago, the historian Michael Bliss composed his remarkably
illuminating recounting of this saga. It has proved to be the definitive
account. Bliss, now a university professor emeritus at the University of
Toronto, has also written highly regarded biographies of the inimitable
physician Sir William Osler, the polymath surgeon Harvey Cushing, and the
fascinating, albeit mercurial, Banting. But as Bliss confides, "The
Discovery of Insulin is my favourite," and the book has now been released in
a 25th anniversary edition, with a new preface and an updated concluding
chapter.

Two great themes permeate the book. First, in Bliss's careful examination,
performed with access to laboratory notebooks, letters, and other primary
documents, the scientific endeavor that resulted in this "unspeakably
wonderful" drug is cast not as a clear and bright moment of discovery, but
rather as a laborious and often messy process of the development of ideas
and techniques, with the fate of the "discovery" hanging in the balance for
months on end. The progression of concepts and experimental strategy that
the Toronto team and their pharmaceutical collaborators made during a
two-year period is staggering. In the wee hours of October 31, 1920, Banting
wrote a note to himself: "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." By December 1921, Collip had
refined an alcohol-based method of extracting insulin from freshly harvested
beef pancreases, and soon thereafter, he developed a method of testing the
potency of each batch of insulin, using rabbits. By the autumn of 1922, the
technique of isoelectric precipitation was extracting remarkably pure
insulin in what would soon be adequate supplies to meet the demand of
countless patients with diabetes.

The second theme, implicit in the first, has to do with the human element.
The development of this drug was intimately tied to the personalities and
circumstances of the developers, for better and for worse. Ambition and
headstrong behaviors led not only to altercations and errors of data
interpretation, but also to creativity and remarkable perseverance. Clinical
engagements with patients who were desperate for insulin, portrayed so
poignantly in the book, saddled the investigators with an almost crushing
sense of responsibility while also spurring them forward. From this view,
the development of insulin was contingent on the interactions among all four
of the major actors, who were dependent on each other. In the end, as Bliss
notes with wise authority, none of the Toronto quartet adequately realized
"that those who understood history would eventually come to honour all of
them. Above all, we would honour their achievement."

Chris Feudtner, M.D., Ph.D., M.P.H.
Children's Hospital of Philadelphia, Philadelphia, PA 19104 

 

 

 

John S Wilkinson, Rome, NY

"A  veteran  is someone who, at one point in his or her life, wrote a blank
check made payable to The 'United States of America', for an amount of up to
and including their life." (Author unknown)

Be very, very careful what you put into that head, because you will never,
ever get it out. -Thomas Cardinal Wolsey (1471-1530)

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