Dr. Banting conceived of ligating the pancreatic duct as a way of destroying the organ’s exocrine tissue that could provide a cleaner collection of the remaining islet cells and their extract, which he called isletin. Dr. Banting and Mr. Best set off to test this theory. They were aided by JJR MacLeod, MD, a prominent physiologist at the University of Toronto, Ontario, who provided them with lab space and 10 research dogs for experimentation before departing for a summer-long trip to Europe.3
The results were startling. Armed with a few syringes, Dr. Banting and Mr. Best moved from bed to bed on the pediatric ward where diabetic children were wasting away, injecting each child with their precious extract of isletin.4 They had nothing to lose. In 1922, a child diagnosed with type 1 diabetes carried a life expectancy of only two years. Their project met with fits and starts; different batches of the extract displayed different potencies. The purification process was further hampered by the strict regulation of alcohol during Prohibition.3 Fortunately, the development of the isoelectric precipitation method led to cleaner, more potent animal insulins, the appellation given to the purer form of isletin.
Word of their incredible discovery quickly spread across the globe. In a matter of just a few years, commercial-grade insulin saved countless lives. The 1923 Nobel Prize in Medicine was awarded to Drs. Banting and MacLeod, a bitter pill for some, considering that Dr. MacLeod was ensconced in Europe for a critical part of insulin’s discovery.3 A final footnote: Dr. Banting and Mr. Best sold their patent rights to insulin to the University of Toronto for a mere $3. Those were the days!
Under the Autoimmune Umbrella
The cause of type 1 diabetes remains unknown. What triggers the selective loss of the islet β cells that results in the dramatic underproduction of insulin? Because diabetes is no longer a fatal illness, scant pathological material exists to study and the enzyme-laden pancreas does not take kindly to needle biopsy procedures. What we do know is that in the early stages of diabetes, an intense inflammatory infiltrate in the pancreas seeks out and destroys islet cells. In fact, clinicians were aware of this hypothesis over a century ago, when salicylates were used to treat diabetes.5
Islet cells lack the ability to regenerate, so efforts to suppress the earliest stages of the type 1 diabetes immune response have met with failure. Consider that a panoply of treatments, including cyclosporine, cyclophosphamide, anti-CD-3 antibodies and, more recently, abatacept, have met with failure.6 Although co-stimulation modulation with abatacept temporarily slowed the reduction in β cell function in patients with newly diagnosed type 1 diabetes, this improvement lagged with continued administration, and eventually, the drug proved to be no better than placebo.7 Similarly, the initial hopes raised by the early success with islet cell transplantation faded. Normal endocrine reserve is not usually achieved in most cases because insulin independence is gradually lost over time.8
