90 Years And Still Going Strong

It needed a timely reminder from Diabetes UK that it is 90 years since the first person was treated with insulin.  And what a fascinating 90 years is has been.

The story actually dates back to the mid-nineteenth century when Paul  Langerhans described the groups of cells known as the Islets of Langerhans in the pancreas without realising what their function was.  Oscar Minkowski and Joseph von Mering later found that when experimenting with a dog, if the pancreas was removed the dog developed diabetes but that if the duct was ligated, it did not.

In the popular mind insulin was discovered by two Canadians at the University of Toronto, Frederick Banting and Charles Best but two other people were heavily involved,  the head of Banting’s department, a Scotsman called John McLeod and another scientist Bertram Collip.

Basically, Banting wanted to explore the functions of islet secretions by performing some experiments on dogs.  He was allotted a laboratory by McLeod, who oversaw the experiments.  Banting co-opted Best who was a medical student and, later when things started to move quickly, Collip.

Things developed rapidly after a dog which had had its pancreas removed was kept alive and its blood glucose level low by frequent injections of islet extract.  Collip was able to purify islet extract.  McLeod suggested the name “insulin” from the Latin word for island.

The first human with diabetes was given insulin in January 1922 and the patient, Leonard Thompson made a dramatic recovery.  Within nine months, the substance had received a product licence (eat your hearts out pharmaceutical companies !) and was manufactured by Eli Lilly who are, to this day, one of the main players in insulin manufacture.

The first cracks in the team came in 1923 when McLeod and Banting were jointly awarded the Nobel Prize in Physiology or Medicine.  Banting was furious and immediately donated half of his prize to Best.  McLeod countered by giving half his prize to Collip.

Within a year, Eli Lilly were producing large quantities of insulin while the European rights had been granted to Nordisk, one of whose partners was Hans Christian Hagedorn who, in 1946, discovered Isophane or Neutral Protamine Hagedorn (NPH)insulin.

For the first 60 years, all insulin was extracted from cow and, later, pigs’ pancreas.  Until the late forties when the longer acting isophane insulin was produced only soluble insulin was available.  This had to be given at least three times a day using syringes and needles that were sterilised between each injection.  Plainly people treated at this time had sub-optimal glycaemic control and yet many survived for many years, indeed some of the earliest people treated with insulin have only just died, having received insulin for as much as 80 years.

For many years all those treated with insulin had Type 1 Diabetes.  The first suggestions of insulin resistance were made by Professor William Falta in 1931 and developed by Sir Harold Himsworth in 1936.  Although Type 2 Diabetes was known and treated with sulphonylureas, metformin and, occasionally, insulin, insulin resistance was almost forgotton until G M Reaven’s ground-breaking Banting Lecture in 1988.  He proposed the existence of also-called “Syndrome X” which later became known as “metabolic syndrome”.  These terms have now almost been abandoned with Impaired Glucose Tolerance (or Pre-Diabetes) and Type 2 Diabetes being the preferred names.

Meanwhile things was starting to progress in insulin.  Until about 1970 soluble and isophane bovine or pork insulin were available in strengths of 20, 40 and 80 units/ml.   The potential for confusion was solved with a wholesale switch to 100 unit/ml insulin.

The pathway to synthetic insulins was laid by Frederick Sanger and Dorothy Hodgkin in the 1950’s and 1960’s; both of whom won Nobel Prizes for their work.  This work led to the synthesizing of insulins by genetically modifying yeast or bacteria to give the so-called “human insulins”.  The latest development came at the end of the century when the first “analogue” insulins became available.  These are produced by recombinant DNA technology (or molecular cloning).

At present there are 2,200,000 people in the UK with diabetes of which about 300,000 have Type 1 Diabetes.  So probably upwards of 600,000 people are treated with insulin. Things have come a long way since Leonard Thompson.

Learning links:
Diabetes Mangement distance learning course
Insulin Conversion study day

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