Insulin: a deadly disease made livable

The rice, roti and potatoes you eat are broken down into a sugar called glucose. It passes into your blood, which carries it to every cell, where it is used for energy Grade 9: Pancreas.

In diabetes, the glucose stays in the blood instead of getting into the cells. The level of sugar in the blood rises far too high, and the kidneys pass some of it out in the urine. That is why doctors in ancient times noticed that the urine of people with diabetes tasted sweet. A person with diabetes:

• passes a lot of urine and is always thirsty;
• is always hungry, yet grows thinner, because the body cannot use its sugar and starts to burn its own fat and muscle;
• in the worst cases, builds up poisonous acids in the blood as the fat is burned, falls into a coma (a deep unconsciousness) and dies.

Before 1922, the only treatment was a strict diet with very little food, sometimes only a few hundred calories a day. It gained a little time, but patients grew weaker and thinner, and some starved.

The pancreas is a long, soft gland behind the stomach. Most of it makes pancreatic juice, which flows through a tube, the duct, into the intestine and helps digest food. One of the strongest enzymes in this juice is trypsin, which breaks down proteins.

In 1869 a German student, Paul Langerhans, noticed small clusters of different-looking cells scattered through the pancreas, like islands in a sea. They are called the islets of Langerhans (islet means a small island).

In 1889 two German doctors, Joseph von Mering and Oskar Minkowski, removed the whole pancreas from dogs. The dogs got severe diabetes and died. But if a small piece of the pancreas was left in, even sewn under the skin, they did not get diabetes. So the pancreas makes something that goes into the blood, not through the duct, and controls the body’s sugar. Scientists guessed it was a hormone (a chemical messenger carried by the blood) made by the islets, and named it insulin, from insula, Latin for island, before anyone had found it.

For over thirty years, scientists all over the world tried to get insulin out of the pancreas. Some extracts lowered the blood sugar a little, but none worked well enough or safely enough to use.

1. The pancreas destroys its own insulin. Insulin is a protein. When the pancreas is ground up, its trypsin is let loose and starts to break proteins down, so the insulin is destroyed.
2. The extracts were impure. They contained many other substances, which caused fever and painful swellings where they were injected.
3. Measuring was slow. Until the 1910s there was no quick, accurate way to measure the sugar in a small sample of blood, so it was hard to tell whether an extract was working.

Banting’s idea (1920)

Frederick Banting was a surgeon who had come back from the First World War, where he was wounded. In 1920 he was a doctor in London, Ontario, and taught part-time at its university. On 30 October 1920, preparing a lecture, he read an article by Moses Barron. When the duct of the pancreas is blocked, Barron wrote, the cells that make the digestive juice shrivel and die, but the islets stay healthy.

Banting had an idea. Tie off the duct of a dog’s pancreas and wait. The juice-making cells, and their trypsin, would die away, leaving the islets. An extract made from what was left should contain the insulin, undamaged.

Toronto (1921)

Banting took his idea to John Macleod, Professor of Physiology at the University of Toronto and an expert on how the body uses sugar. Macleod was doubtful, but he gave Banting space in his laboratory over the summer, some dogs, and an assistant: Charles Best, a 22-year-old student who knew how to measure blood sugar.

1. Tying the ducts (spring 1921). They tied the pancreatic ducts of several dogs. Weeks later, the pancreas of each dog had shrunk to about a third of its size, with no healthy juice-making cells left.
2. The first extract (summer 1921). They chopped up the shrunken pancreas, ground it with sand in cold salt water, filtered it, and injected it into dogs whose pancreas had been removed. The dogs’ high blood sugar fell, and they grew stronger.
3. A better source. Tying ducts gave very little extract. Banting found that the pancreas of a calf before birth contains plenty of islets and almost no trypsin. Then they found that alcohol with a little acid pulls the insulin out of an ordinary cow’s pancreas, from the slaughterhouse, without letting the trypsin destroy it. The duct-tying trick was no longer needed.
4. A dog kept alive. Dogs without a pancreas usually died within two weeks. With daily injections of extract, they kept one healthy for ten weeks.

The first patients (1922)

In December 1921 Macleod brought in James Collip, a biochemist, to make the extract purer. At the same time the team began to test it in people.

1. 11 January 1922. At the Toronto General Hospital, the extract was injected into Leonard Thompson, a thin, weak teenage boy close to death from diabetes. The extract was too impure. His blood sugar fell only a little, and he got a painful swelling where it was injected.
2. 23 January 1922. Collip had found a better way to purify it. Leonard was given the new extract. This time his blood sugar fell to normal, the sugar in his urine almost disappeared, and so did the dangerous acids. He lived for another thirteen years.
3. More patients. Children who had been carried in, too weak to walk, began to eat normally and put on weight. Patients woke up from diabetic coma, which until then had always ended in death.

Making enough for everyone (1922–1923)

There were thousands of dying patients, and the team could make only a little insulin at a time. Best worked on making it in large amounts at the university’s Connaught Laboratories, and the American drug company Eli Lilly joined in. By the end of 1923, insulin was being made from the pancreases of cattle and pigs from slaughterhouses, and was in use in many countries.

Banting, Best and Collip patented the method so that nobody could take it over, then sold the patent to the University of Toronto for one dollar each. They wanted insulin to be made well and sold fairly, not to make money from it.

The islets contain several kinds of cells. The beta cells make insulin. After you eat, the glucose in your blood goes up. The beta cells notice and release insulin into the blood.

Insulin works like a key. When it reaches a muscle or fat cell, it attaches to the outside of the cell and “unlocks” it: little doors open in the cell’s skin and let glucose in. Insulin also tells the liver to store glucose as glycogen, a kind of animal starch, for later. So the sugar in the blood comes back down. Between meals, another hormone from the islets, glucagon, does the opposite: it makes the liver release glucose, so the blood sugar doesn’t fall too low.

There are two main kinds of diabetes Grade 10: Diabetes:

• Type 1. The body’s own defense cells destroy the beta cells, usually in childhood or youth. The body makes almost no insulin, so the person must take insulin, by injection or pump, every day. This was the deadly disease that insulin turned around.
• Type 2. Far more common, mostly in adults. The body still makes insulin, but the cells don’t respond to it well, and in time the pancreas can’t keep up. It is linked to being overweight and not exercising. It is treated with diet, exercise and tablets, and sometimes insulin.

• Millions of lives. More than 9 million people in the world live with type 1 diabetes (as of 2025). Without insulin, they would not survive.
• Diabetes in Nepal. Type 2 diabetes has become common in Nepal, as in most of the world, as people eat more sugar, oil and white rice and move less. Many people who have it don’t know. Walking, cycling, playing sport and eating fewer sweets and sweet drinks lower the risk.
• Low sugar is dangerous too. Banting found that too much insulin makes the blood sugar fall too low: the person sweats, shakes, feels anxious and confused, and may faint Grade 9: too much insulin. If someone with diabetes feels like this, they need sugar quickly: a sweet drink, juice or glucose.
• World Diabetes Day, 14 November, is Banting’s birthday.

• Insulin’s structure. In the 1950s Frederick Sanger worked out the exact order of the building blocks in insulin, the first protein ever to be read this way. He won the Nobel Prize in Chemistry in 1958. In 1969 Dorothy Hodgkin worked out its shape in three dimensions with X-rays (Dorothy Hodgkin’s prize).
• Human insulin from bacteria (1982). Scientists put the human gene for insulin into bacteria, which then made human insulin. Since then most insulin has been made this way, instead of from cattle and pigs (How does a gene make a protein?).
• Price. In some countries insulin has become very expensive, a hundred years after its discoverers sold the patent for a dollar. Making it affordable everywhere is still a problem.
• An open question: a real cure. Insulin replaces the missing hormone, but it doesn’t bring back the beta cells. Scientists are now growing new beta cells from stem cells and putting them into patients. In early trials a few people with type 1 diabetes have been able to stop injecting insulin for a year or more (as of 2025), though they need medicines to stop their body attacking the new cells. Can the body’s attack be stopped for good?

• Grade 9: Endocrine glands, Mixed glands and the Pancreas, with insulin, glucagon and blood sugar.
• Grade 10: Diabetes.
• Going further: The feedback loop (how insulin and glucagon keep blood sugar steady) and Proteins do the work.

• The prize at nobelprize.org: The Nobel Prize in Physiology or Medicine 1923, with the presentation speech, which tells the history of the search.
• Banting’s Nobel lecture, “Diabetes and insulin”, and Macleod’s Nobel lecture.

The prize was given “for the discovery of insulin.”

This prize at nobelprize.org(opens in a new tab)