The Amazing History of Insulin Invention

The history of Insulin and the course change of a disease


 

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he insulin history is filled with trials and errors like so many other great discoveries and many have contributed. Insulin was discovered in 1921 and since then it has become one of the most studied molecules in history. Diabetes have been known to men for at least 3,500 years but the causes have been a puzzle for a long time. The full causes of diabetes have only been discovered in the 1020’s. At first scientist though diabetes were only related to the digestive system but they also had clues, all leading to the pancreas. Before recent discoveries the only way to control high blood glucose was with diet low in carbohydrates and sugars and high in fat and protein. Diet alone was not enough and patients would die within a year or so after diagnosis; it was so hard to keep patients in these harsh diets some would die of starvation. This acuity in death might might have been an indication that these earlier cases might very well have been of diabetes type I. It is hard to know the ratio of diabetes type I and type II in the past since very little was known about diabetes.

The first real clue of what caused diabetes appeared in the 19th century when it was observed that patients who have died of diabetes all presented damaged pancreas. In 1869 a German medical student named Paul Langerhans discovered a cluster of cells in the tissues responsible for the production of digestive juices in the pancreas; the exact functions were unknown. Eventually, much later it was discovered that these cells produced insulin, so these clusters were named “islets of Langerhans” in his honor.

The groundwork for the discovery of insulin had the contribution of several others who made it possible for insulin to be first purified in 1921. Two European researches, Minkowski and von Mering, found that when the pancreas gland was removed from dogs they would develop all signs and symptoms of diabetes and died soon afterwords. It was then first established that the pancreas was central for sugar metabolism and its implications in diabetes was clear.

In 1910, Sharpey-Shafer of Edinburgh proposed that a single chemical was missing from the pancreas of diabetics; narrowing the search to the Islets of Langerhans specialized cells within the pancreas. He proposed that this chemical would be called “insulin” which would be later be adopted by Canadian researchers. An American scientist named E.L. Scott was trying and almost succeeded in creating a insulin extraction using alcohol. In Romania R.C. Paulesco made an extract from pancreas tissue that lowered blood glucose in diabetic dogs. Some claim Paulesco to be the first to produce insulin.

The major breakthrough in the insulin history would come in the summer of 1921 when Frederick Banting and Charles Best performed a series of experiments in the laboratory of J.J.R. Macleod and the University of Toronto. They first showed that removing the pancreas of dogs would make them diabetic much in the same way Minkowski and von Mering had previously demonstrated.

The experiments continued to be improved as they took fluids directly from Islets of Langerhans of healthy dogs and injected into diabetic dogs restoring them to normalcy for as long as the extract was available. Later they were able to successfully extract a reasonably pure formula of insulin from the pancreas of cattle from slaughterhouses.

A teenager with diabetes type I in a Toronto hospital named Leonard Thompson was the first person to receive an injection of insulin. The treatment was a success as the boy improved dramatically and the news spread around the world in a flash. Banting and Macleod received the Nobel Prize in Medicine the very next year in 1923. Royalty free licences were granted by the University of Toronto and by 1923 one year after the fist injection insulin, it became immediately available worldwide saving countless lives.

In 1926 insulin was one of the first proteins to be crystallized in pure form. The importance of this discovery allowed scientists to study its structure with a technique called x-ray crystallography and approximate its three dimensional shape. To know a molecule’s shape helped to understand how it could work in the body. Since then scientists have tried to understand how insulin works and what other molecules might interact with it.

Insulin became the first protein to be fully sequenced in 1955. Frederick Sanger received a Nobel Prize for his work. Thanks to his work we know that all human proteins have a unique sequence of 20 types of amino acids. These amino acids are strung into chains called peptides; like letters in long words.

Once protein’s sequencing is known, it is possible at least in theory recreate it synthetically. In 1963 insulin became the first protein to be chemically synthesized in a laboratory. The only draw back was the difficulty producing significant amounts of it. For 60 years insulin relied on hormone purified from cattle and pigs after its production have been discovered by Banting’s. Even though insulin from animals worked well overall it sometimes caused adverse effects such as skin rashes. Finally in 1978 insulin became the first human protein to be produced by biotechnology. Genentech manage to synthesize human insulin in the laboratory using a process which enabled production in large amounts.

A team of researchers from the City of Hope National Medical Center inserted the gene for human insulin into bacterial DNA, and used the bacteria as a miniature manufacturing center to make the A and B chains of the protein separately; a second step combined them. Humulin was born as a commercial product revolutionizing diabetes treatment in the early 1980’s. Today almost all diabetics use recombinant human insulin instead of animal insulin.

There is however a lucky turn of events. Bovine insulin worked in the 1920’s by pure luck and scientists didn’t even know about it. It turns out that the amino acid sequence of insulin is almost exactly the same in different animal species. Insulin from cows and pigs also works in humans. Insulin’s basic structure – two peptide chains with three disulfide bridges.

Looking in more details however reveals that the sequence of pig insulin and human insulin is almost identical; it differs by one amino acid. Bovine insulin differs in three amino acids. This is why animal insulin could be used but scientists didn’t know that at the time. The Food and Drug Administration approved a modified human insulin called Humalog in 1996 specially developed for quick action after injection.

Insulin history and the future 

Researchers are now looking at new forms of delivery via the lungs. Eli Lilly has a project with Dora Pharmaceuticals and is researching this alternative system. Bio-engineers are looking into the creation of beta cells in a semi-permeable membrane which would restore the lost pancreatic functions, there are still issues concerning organ rejection. These are a few examples of new developments as the history of insulin continues into the future. The continued efforts of science and individuals on a daily basis add invaluable contributions for a better management and possible cures.

 

 


Videos

Jim Turner takes us through this 3 part special on how insulin became commercially available, and saved millions of lives.

Part I


 

Jim Turner takes us through this 3 part special on how insulin became commercially available, and saved millions of lives.

Part II


 

Jim Turner takes us through this 3 part special on how insulin became commercially available, and saved millions of lives.

Part III


 

Insulin and Diabetes: The amazing story of Eva Saxl, a Holocaust refugee who survived WWII with her husband’s homemade insulin.

 


 

Diabetes Patient Education Types of insulin

 


 

Image credits: flickr.com Wikipedia, University of Toronto, PBS

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