Sugar, Dogs, Cows, and Insulin—The Story of How Diabetes Stopped Being Deadly

Before the discovery of insulin, diabetes was a life-threatening and untreatable illness. It was caused by very high blood sugar levels and many children died from it. In 1922, two scientists, Frederick Banting and Charles Best, treated a boy suffering from diabetes with special extracts from a cow’s pancreas. The pancreas is an organ found near the stomach. The treatment lowered the boy’s blood sugar to normal levels due to a chemical substance from the pancreas. This substance was later named insulin. In this article you will read about diabetes and insulin. You will see that the final discovery of insulin built on the work of many scientists before Banting and Best. It is a great story showing how the skills and determination of different people together led to a ground-breaking discovery. In 1978, human insulin was made artificially from bacteria and today it continues to save millions of lives.


WHAT IS DIABETES?
A high level of sugar in the blood can be dangerous and is the main sign of an illness called diabetes. Before insulin was discovered, many DIABETES A condition in which glucose levels in the blood become dangerously high. In type diabetes, insulin is not produced by the pancreas. In type diabetes, the body does not respond to insulin and the pancreas does not make enough insulin.

INSULIN
A chemical substance made by cells in the islets of Langerhans. The main role of insulin is to help the body to use glucose as a source of energy.
people died from this illness. Diabetes has been known for a long time.
The Egyptians wrote about it in medical scrolls more than , years ago in the Ebers Papyrus [ ], and there are records of treatments for diabetes dating back to ancient India and China [ ].
Aretaeus of Cappadocia, a Greek doctor in the nd century AD, first used the word "diabetes," which means "siphon" or "pass through." This word was chosen because people with untreated diabetes needed to urinate a lot, as if water flowed through their bodies. Other old medical writers described how the body wasted away and suggested that "waste" was lost in the urine. This fits with another sign of the illness, weight loss. Other symptoms include thirst, hunger, and tiredness.
The full medical name of diabetes is diabetes mellitus. Mellitus means "sweetened with honey" and was chosen because of the presence of sugar in the urine, which is caused by high levels of sugar in the blood. The sweetened urine attracts insects. Nowadays we can measure blood sugar levels directly, but before that was possible, diabetes was sometimes detected by testing whether or not ants were attracted to the sweetness of the urine.
The problem with diabetes is that, although there is plenty of sugar in the blood, the body cannot use it and instead eliminates it in the urine. Glucose is the most common type of sugar in the body and it GLUCOSE Carbohydrate from the diet is made up of smaller units. Glucose is the most common and important of these units as it is the main source of energy fuel for the body.
is the main source of energy for the body's cells, including the brain cells. When someone has diabetes, the cells cannot get access to glucose and starve instead. To solve this problem, the body makes energy from fat instead of glucose. A side e ect of this process is that the blood becomes very acidic. This is called ketoacidosis and KETOACIDOSIS A condition in which the blood becomes acidic due to the production of high levels of ketone bodies. When glucose is not available, the liver makes ketone bodies from fat molecules to provide energy for the brain. it can cause a person to go into a coma or even die. It is therefore extremely important to help the cells use glucose and to lower blood glucose levels.

DIFFERENT TYPES OF DIABETES
There are at two main types of diabetes, type and , and both are linked to a substance called insulin. Insulin is a chemical that is normally made by the body and it controls blood glucose levels, mainly by signaling to cells that they need to take up glucose from the blood. In type diabetes, people cannot make insulin. In type diabetes, insulin is at first being made, but the cells cannot respond to it properly. This is referred to as insulin resistance. In both cases, glucose is not moved into the cells. With time, people who develop type diabetes also become less good at making insulin.

Hauge-Evans
The Discovery of Insulin

Figure
The pancreas is located next to the stomach, liver, and small intestine. In this image the stomach is not shown, so you can see the pancreas. The duodenum, which is the top part of the small intestine, is connected to the stomach (figure modified from Freepik.com resource).

WHAT CAUSES HIGH LEVELS OF GLUCOSE IN THE BLOOD?
Our bodies get energy from the foods we eat. The main parts of food

INSULIN RESISTANCE
A condition in which cells do not detect or respond to insulin. Insulin-resistant cells fail to take up glucose from the blood and thus cannot use glucose for their energy needs.
are fats, carbohydrates, and proteins. Carbohydrates are an essential energy source and are found in foods, such as bread, rice, and pasta but also in fruit, vegetables, and dairy products. Carbohydrates are broken down in the stomach and intestine into smaller units, including glucose. In the small intestine, glucose is transferred into the blood stream. Therefore, glucose levels in the blood increase after a meal. Normally, the blood will transport the glucose to cells all over the body, where it is taken up with the help of insulin and used as a source of energy.
Some famous experiments in by two German doctors, Oskar Minowski and Joseph von Mering, showed that an organ next to the stomach and the liver called the pancreas (Figure ) is also essential PANCREAS An organ which helps the conversion of food to energy in the body by producing chemical messengers (hormones), such as insulin. It also makes digestive enzymes, which help break down food in the small intestine.
for controlling blood glucose levels. If the pancreas was removed in dogs, the animals would very rapidly develop serious signs of diabetes [ ].

WHAT IS SPECIAL ABOUT THE PANCREAS?
In , a medical student named Paul Langerhans was studying a rabbit pancreas under the microscope. He saw something interesting-not all pancreatic cells were the same. There were clusters of similar-looking cells dotted throughout the pancreas like small islands in the sea. Langerhans did not know why the cells were arranged this way or whether they were di erent from the rest of the pancreas. In , these small mini-organs were named islets of Langerhans by another scientist, Edouard Laguesse, who saw the

ISLETS OF LANGERHANS
Groups of cells located in the pancreas. They are responsible for the production of insulin and other hormones from the pancreas. same pattern in the human pancreas. We now know that there are about one million of these islets in a human pancreas (Figure ). Laguesse suggested that these islets could make a chemical that might regulate blood glucose levels, but at that time it was just an idea.
Other observations helped scientists develop this idea further. The pancreas is connected to the small intestine via a tube called the pancreatic duct. If this tube was blocked experimentally, all the non-islet cells eventually died. However, the islets kept their normal structure for much longer, which confirmed that islets really were di erent from the rest of the pancreas.
Scientists also noticed that urine glucose levels did not increase in animals that had their pancreatic ducts blocked, because their islets were still working. In contrast, glucose levels were high in animals that had the whole pancreas removed. These types of experiments were carried out by many di erent scientists from Italy, Germany, France and the UK around the turn of the th century [ ]. They suggested that only the islets, and not the rest of the pancreas, control blood glucose. It was later discovered that the islets control blood glucose levels through the production of insulin. Getting the insulin out of the islets was more di cult, and they had to repeat their experiments many times to get the insulin pure enough. Together with another team member, James Collip, they were eventually able to remove unwanted chemicals and concentrate the insulin from the pancreas. Banting also learned that they could use pancreas extract from cows rather than dogs. This was an important finding, because the cow pancreases were available from animals already killed for food, and much more insulin could be extracted. Excitingly, the scientists found that the purified insulin reduced blood glucose levels when it was injected into diabetic animals and then they were ready to test the extract in humans [ ].
Banting and Best worked across the road from a hospital where a -year-old boy named Leonard Thompson was a patient, su ering from diabetes. On th January , Thompson was injected with the insulin made by Collip, Best, and Banting, but unfortunately it did not work. Collip then made an even purer extract, which was used on January -this time it worked! Leonard's blood glucose levels went down, his blood became less acidic, and he felt a lot better [ ]. The same happened when six other people on the ward received the treatment.
This was the turning point-it meant that diabetes was no longer deadly. But there was still work to do. Large amounts of insulin were needed, so scientists developed methods of scaling up its production. They also discovered the genetic code for human insulin and set up clever experiments in which that code was inserted into bacteria that would then make large amounts of human insulin. In , human insulin was made from bacteria for the first time and it continues to save millions of lives today.

ONE DISCOVERY-MANY SCIENTISTS
Banting and MacLeod received the Nobel Prize in , but the discovery of insulin was due to the work of many scientists. It started with medical observations in the ancient world and went on to involve people from countries across Europe and America. Scientists throughout the world still carry out diabetes research. Some scientists work on improving diabetes treatment and others investigate why islets stop making insulin in the first place. Some study whether certain cells can be changed to become like islets, so that they will make insulin. But the ultimate aim is to one day find a way to prevent or even cure diabetes, which will improve and save the lives of millions of people around the world. . The discovery of insulin: an important milestone in the history of medicine. Front. Endocrinol.

CONFLICT OF INTEREST:
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AUTHOR
ASTRID CHRISTINE HAUGE-EVANS I am a scientist in the Department of Life Sciences at University of Roehampton in London, UK, where I teach Nutrition and Health. I am interested in how the pancreatic islets make insulin and how this process sometimes fails in diabetes. There are many factors both inside and outside the body which a ect this process. They include signals from the brain, the stomach and gut, as well as signals from cells within the islets. I am interested in how the cells in the islets talk to each other and change the production of insulin. I am also studying how other things in our diets, such as co ee and whole grains, can improve or worsen how well the islets make insulin. *Astrid.Hauge-Evans@roehampton.ac.uk