100 years of insulin

A century of dramatic breakthroughs have led to the insulin therapy we are lucky to have access to today. Marlon Moala-Knox investigates.

Before the discovery of insulin, type 1 diabetes was almost impossible to treat. Putting patients on strict diets might lengthen their life by a few years, but dying young was still the norm, and sometimes the diets themselves killed the patients – they were eating too little to survive.

This was the reality for people with type 1 up until about 100 years ago, when production of insulin for medical use started.

Before it could be used as a treatment, however, we first needed to know it existed.

HOT ON THE TRAIL OF INSULIN

It was about 150 years ago that Western science began to figure out what that long organ behind the stomach – the pancreas – might be for.

In 1869, German medical student Paul Langerhans was studying the pancreas when he noticed that, scattered throughout it, were interesting clumps, or ‘islands’, of cells. Noone was sure what they did, but they were given the name ‘the islets of Langerhans’.

Some researchers thought they might play a role in regulating digestion. So, in 1889, two German physicians, Oskar Minkowski and Joseph von Mering, surgically removed the pancreas of a healthy dog to see how it affected its digestion.

What they discovered was that the dog immediately developed symptoms of diabetes. This was the first time a link was established between diabetes and the pancreas.

From 1910, Sir Edward AlbertSharpey-Schafer, an English physiologist – sometimes regarded as the founder of endocrinology – began to theorise that the only thing missing from the pancreases of people with diabetes was a single hormone. He found that the islets of Langerhans made a chemical that metabolised glucose, and he named this ‘insulin’ after the Latin word for island: ‘insula’.

However, attempts to extract insulin from the pancreas were unsuccessful. Enzymes from the pancreas kept destroying the insulin during the extraction process.

That was, until 1921.

FIRST SUCCESSFUL INSULIN EXTRACTION

One hundred years ago, Canadian medical researcher Frederick Banting and his assistant Charles Best found a way to extract insulin by inducing atrophy (a kind of shrivelling) in a dog’s pancreas, while leaving the islets of Langerhans intact.

Banting and Best then managed to keep a dog with diabetes alive for an extended period by injecting it with insulin extracted from a non-diabetic dog’s pancreas.

Now that this method was proven to work, Banting and Best teamed up with their colleagues John Macleod and James Collip to develop the process further. Their goal was to extract insulin in a purer form, and in quantities large enough for practical use in diabetes treatment.

INSULIN THERAPY TAKES OFF

It’s thought that the first human patient to be treated with insulin was Leonard Thomas, a 14-year-old boy with type 1 diabetes at Toronto General Hospital who was close to death.

His first injection of insulin went wrong – impurities in the extract gave him an allergic reaction. However, after the researchers further refined their methods, and Thomas began receiving daily doses of much purer insulin, he went on to make an almost full recovery.

He continued taking insulin for the next 13 years until his death from pneumonia. Though complications from diabetes were likely a major factor in his death, living for over a decade after a diabetes diagnosis was a huge improvement compared to living only few weeks or months, as had been usual before insulin was discovered.

Research and development of insulin treatment continued, now mostly using insulin from the pancreases of cows and pigs. Soon Eli Lilly and Company, an American pharmaceutical firm, made a deal with the Canadian researchers and began the first mass-production of insulin.

In 1923, Banting and Macleod were awarded the Nobel Prize in Physiology or Medicine, and, although it’s widely attested that, in reality, these men didn’t get along with each other, they split the money with Best and Collip.

Over the next few decades, diabetes treatment advanced rapidly, with innovations such as slower-acting insulin, and, eventually, the use of bacteria to produce and extract insulin identical to that of the human pancreas. This was a huge improvement. Cow and pig insulin don’t perfectly match ours and can cause complications.

INSULIN DELIVERY

The methods we use for administering insulin have changed a lot since it was first discovered. To begin with, insulin was delivered using heavy, painful syringes with large-bore needles (pictured below). The needles were reusable, but you had to sterilise them before each use by boiling them in water.

In 1924, the first specialised insulin syringe was produced by the American medical technology company Becton Dickinson. And, in 1954, Becton Dickinson introduced the first disposable glass insulin syringe.

Despite advances, using syringes could still often be unpleasant or painful, and getting the dosage right was difficult. People with diabetes tended to struggle psychologically with having to painfully inject themselves multiple times a day, and this often resulted in a lack of blood sugar control as people skipped injections.

PENS AND PUMPS ARRIVE

Novo Nordisk launched the first insulin pen in 1985. Compared to syringes, pens are much easier to use, as well as being more discreet and cost-effective.

By the 1990s, finer needles had been developed as well, greatly reducing the pain associated with injecting insulin.

The first prototype of an insulin pump was developed in 1963 by Californian doctor Arnold Kadish. It was the size of a large backpack, and had to be worn like one, strapped on to the user (pictured, below).

In 1973, Dr. Ernst Friedrich Pfeiffer, from Germany, developed a fully functioning insulin pump called the Biostator. It was still too large and complicated for anyone to use it daily, but it was proof that insulin pumps could work, and was a technological stepping stone towards more practical designs.

In 1976, the first wearable insulin pump small enough for practical use was developed by US inventor Dean Kamen, finally leading to the first real uses of insulin pump therapy.

In 1986, MiniMed introduced the first implantable insulin pump.

THE NEW MILLENNIUM

Advances in insulin therapy and its delivery are coming rapidly now. Closed loop systems or ‘artificial pancreases’ – which combine blood sugar monitoring with fully automated insulin delivery – are becoming more accessible. They remain out of the reach of many because of cost, but perhaps that will change.

One thing is certain – for over a hundred years, researchers have been working innovatively and determinedly to improve the lives of those who need insulin because of diabetes. For any of us affected by diabetes, whether we have it or a loved one does, that’s cause for celebration.

Marlon Moala-Knox is a Wellington writer and researcher whose younger sister lives with type 1 diabetes.