Editorial
Endocrinology
Volume 199 - Issue 4

The history of insulin: the mystery of diabetes

Author:  Stephen R Leeder

Med J Aust 2013; 199 (4): 227. || doi: 10.5694/mja13.10973
Published online: 2 September 2013
Since ancient times, this disease has inspired mythology as well as discovery, and continues to challenge us today.
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Drawing inspiration from our forebears in scientific inquiry to face emerging global challenges

Adisease as ancient, prevalent and serious as diabetes attracts mythology, and the edges of its history blur. The ancient Greek word diabetes, originally deriving from the verb diabainein, “to pass through”, was the name for a “siphon”, referring to the associated polyuria. Aretaeus of Cappadocia (around the first century CE) was probably an early adopter of the word although another source suggests it was first used by Apollonius of Memphis around 250 BCE. Mellitus, meaning “honey-sweet”, was added by the British physician Thomas Willis in 1675 “after rediscovering the sweetness of urine and blood of patients (first noticed by the ancient Indians)”.1 However, it was not until 1776 that another British physician, Matthew Dobson, identified excess sugar in urine and blood as the cause of their sweetness.1

In 1889, Joseph von Mering and Oskar Minkowski (variously described as physicians or physiologists, depending on the source) in Strasbourg reported that they had been able to render dogs diabetic by removing the pancreas — Minkowski must have been surgically deft, whatever his other professional skills. Mythology has it that their experimental animal keeper noticed ants (or bees in another account) enjoying the urine of pancreatectomised animals. The surgery was performed in pursuit of better understanding of the digestive organs, and this discovery was made serendipitously.2

With increasing attention paid to the pancreas, ideas developed and imagination flourished. Its exocrine and endocrine functions became clearer. Frederick Banting, a 24-year-old orthopaedic surgeon in Toronto, sought to ligate the exocrine outlet to produce atrophy of that part of the pancreas, thus, he hoped, allowing the endocrine part to be studied, undigested by the pancreatic juices. With the aid of a medical student, Charles Best, Banting ligated the pancreatic ducts of a dog. As a result, the exocrine cells in the pancreas atrophied, leaving the insulin-producing islet cells. From the islets, Banting and Best produced pancreatic extracts with which they were able to ameliorate the diabetes produced by surgical removal of the dog’s pancreas. Much work followed, leading to the acrimonious award of the Nobel Prize in Physiology to Banting and head of the department where he did his work, John Macleod.3

The developments since have been phenomenal achievements in what we now call translational research. They have been realised through clinical commitment, academic competition, private enterprise by pharmaceutical companies purifying and mass producing insulin, and government support. The nature of diabetes has continued to yield complex mysteries — what once appeared to be a straightforward deficiency disorder is now known to be exceptionally complex. Insulin resistance and metabolism more generally continue to give rise to fascinating insights.

As a second-year medical student in 1960, I shared the amazement that the A and B chains of insulin had been sequenced, after Frederick Sanger received the Nobel Prize for this remarkable feat in 1958. Since then, of course, we marvel at the complex studies of the insulin molecule and the recombinant technologies that have enabled its mass production and modification.

But diabetes has admitted no easy defeat, and the current global epidemic of type 2 diabetes has shown just how much more we have to learn about the metabolic context of the disease. The seeming simplicity of attributing type 2 diabetes to obesity has begun to yield to a deeper appreciation of the underlying metabolic upheavals that occur in the form of the origin and the expression of this disease. The epidemiology of both type 1 and type 2 diabetes raises questions about regional variations in susceptibility, genetic variability and environmental factors — there is much more to be learned. We know enough to do something, but not enough to do everything.

Insulin reminds us of the power of scientific inquiry and our remarkable contemporary capacity to intervene for good. That tens of thousands of people die worldwide each year for lack of insulin, and 50% of the estimated 200 million people with diabetes remain undiagnosed, should give us pause for thought alongside this celebration. In relation to type 2 diabetes, we face challenges of a different sort, although no less complex. Much has been achieved, but much remains to be done.

Provenance: Commissioned; not externally peer reviewed.

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