Book Review

The Discovery of Insulin

N Engl J Med 2008; 358:975-976February 28, 2008

Article

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.

Photographs 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
feudtner@email.chop.edu