A man with diabetes using an injection pen to administer insulin

History of insulin

Rosie Cotter explores the history of this important protein and its role in diabetes

In 1922, a 14-year-old boy named Leonard Thompson lay in Toronto General Hospital dying from diabetes. He weighed less than 30 kg and was at risk of slipping into a diabetic coma. To avoid this, Leonard’s father allowed him to be injected with a new pancreatic extract, now known as insulin.

At the time, people with diabetes tried to control their condition through a strict diet, but they usually died within a year of diagnosis. Remarkably, after the injection, Leonard regained his strength and appetite and went on to live for several more years.

News of insulin and Leonard’s recovery spread around the world and brought notoriety to Dr Frederick Banting and student George Best at the University of Toronto. With the support of Professor John Macleod and biochemist Bertram Collip, Banting and Best had successfully extracted insulin from an animal pancreas and purified it so that it could be administered to humans.

Insulin is a hormone that regulates glucose levels in the blood. When we eat, our glucose levels rise and insulin is released into the bloodstream. Insulin works by regulating glucose transport proteins in cells so they can take up the glucose and use it as an energy source or convert it to glycogen for storage.

Type 1 diabetes develops when the insulin-producing beta cells of the islets of Langerhans found in the pancreas have been destroyed and the body is unable to produce insulin. Type 2 diabetes develops when the body can still make some insulin, but it is produced in insufficient amounts or in a form that does not work properly.

Discovery and application

Between 1920 and 1921, Banting and Best had been removing dogs’ pancreases to make them diabetic. Building on the work of other researchers, Banting and Best took fluid from healthy dogs’ islets of Langerhans (cells within the pancreas that produce insulin) and injected them into the dogs with diabetes to reverse its effects.

The dogs remained healthy for as long as they were injected with the extract. Subsequently, Collip purified the insulin so it could be used on humans.

The researchers’ work led to the widespread use of animal insulin to treat diabetes. Banting and Macleod were awarded the Nobel Prize in 1923 for the discovery, sharing the prize money with Best and Collip. For the next 60 years, people with diabetes relied on animal insulin – usually from pigs or cows – to survive.

Sequencing insulin

In 1955, insulin became the first protein to be sequenced. Biochemist Fred Sanger took on the challenge of determining the amino acid sequence of insulin, which had never been done before.

He developed a method to ‘read’ the amino acid sequence that involving splitting insulin into fragments and carrying out techniques called electrophoresis and chromatography on these.

He found that insulin is made up of two amino acid chains linked together by disulphide bonds, and it is because of this discovery that we know that every human protein has a unique sequence of any or all of the 20 types of amino acids. Sanger was awarded the Nobel Prize in 1959 for the discovery.

Chemical synthesis and structure

Insulin also became the first protein to be chemically synthesised, in 1963. Researchers were unable to produce it in large quantities, however, so people continued to rely on animal insulin to treat diabetes. Although animal insulin worked well, it wasn’t an exact match to the human hormone and some patients suffered minor side-effects, including immune reactions to the hormone.

Nobel Prize winner Dorothy Hodgkin deciphered the molecular structure of insulin in 1969 using X-ray crystallography. Knowing the structure meant that scientists could begin to understand more about the properties of insulin, such as how it is formed, which receptors it binds to and how it is made and transported around the body. Having this kind of information is invaluable for understanding more about conditions such as diabetes and how to treat them.

Large-scale manufacturing

The type of insulin used today came about in 1978 when researchers were able to manufacture a form of human insulin using biotechnology. Scientists genetically modified bacteria to produce the separate A and B chains that make up human insulin and combined these through a chemical process.

The result? The mass production of synthetic human insulin. This revolutionised the treatment of diabetes because it meant that insulin could be produced on a mass scale and used without the side-effects associated with animal insulin.

Lead image:

A man with diabetes using an injection pen to administer insulin.

Wellcome Library, London

References

Questions for discussion

  • How does Banting and Best’s method of testing their extract differ from how we test new treatments today?
  • Banting and Best’s research built on the discoveries of several scientists working before them. What else can you find out about these researchers and their contributions to the discovery of insulin?

About this resource

This resource was first published in ‘Proteins’ in January 2014.

Topics:
Cell biology, Health, infection and disease, Biotechnology and engineering
Issue:
Proteins
Education levels:
16–19, Continuing professional development