The credit for the discovery of insulin most often goes to Canadian physician Frederick Grant Banting (1891, 1941), Scottish biochemist and physiologist John James R.
Macleod (1876, 1935), and Canadian medical scientist Charles Best (1899, 1978).
Although earlier researchers had suggested that the pancreas secreted a substance that controlled the metabolism of the body’s blood sugar, it was not proven until 1922, when Banting, Macleod, and Best announced their discovery.
In 1921, they had begun experimenting on dogs, removing the animals’ pancreases, essentially making the dogs diabetic.
They would then grind down the animals’ organs and extract a solution they called isletin.
Injecting the solution into other animals resulted in a drop in blood sugar levels.
By January 1922, they formulated an extract, this time from cattle pancreases, to try on humans with type 1 diabetes (see Leonard Thompson, below).
When Thompson had an allergic reaction, Canadian biochemist James Bertram Collip (1892, 1965) worked for about 11 straight days, making the injection more “pure” for humans.
The new solution worked, and after several more patients were treated successfully, insulin eventually became one of the best treatments for people with diabetes.
Did any other researchers come close to discovering insulin?
Yes, several other researchers came close to discovering, extracting, and developing insulin.
The list is long and often confusing.
Some people claim that certain researchers came close but did not understand what they were witnessing.
Other historians believe certain researchers should have been given more credit for their discoveries.
And there is also a political, social, and infighting aspect of science in the early days before, during, and even after the first insulin trials.
The following lists some of the more well-known cases in the history of insulin (and some of these events are often highly debated by historians):
Canadian physician and Nobel laureate Frederick Banting was co-discoverer of insulin.
• In 1889, two European researchers, German physiologist and pathologist Oskar Minkowski (1858, 1931) and German physician Joseph Freiherr von Mering (1849, 1908), working at an institute in Strasbourg headed by an authority on diabetes, German pathologist Bernhard Naunyn (1839, 1925), discovered that when the pancreas was removed from dogs, the animals would develop symptoms of diabetes. The researchers suggested that the pancreas was crucial to the body’s sugar regulation and metabolism.
• American physiologist Ernest Lyman Scott (1877, 1966) conducted blood-sugar experiments on dogs.
If a dog’s pancreas was removed, he noticed the animal’s blood sugar would rise.
He then isolated secretions from the pancreas (what is now known as insulin) and injected the dog, causing its blood sugar level to lower.
Thus, he is often credited as the first person actually to extract insulin (in 1911; insulin for medical use was introduced in 1923).
In addition, he is most well known for developing the standard blood test for diabetes in 1914.
• Romanian physiologist and professor of medicine Nicolas Constantin Paulescu (also seen as Paulesco; 1869, 1931) worked to identify the active pancreatic substance that Minkowski and von Mering suggested could be used to treat diabetes. In 1916, he isolated the substance and called it “pancrein,” or what is now called insulin. Thus, Paulescu is often suggested as the discoverer of insulin (and why some researchers believe Paulesco and Scott should have been credited with discovering insulin).
• But in the end, the Nobel Prize in Physiology or Medicine in 1923 was awarded to Banting and Macleod, as they were the first known actually to develop insulin for human use. (Banting shared his half of the prize with Best, while Macleod shared his half of the prize with Collip.)
Who was Elizabeth Evans Hughes?
Elizabeth Evans Hughes (later Gossett; 1907, 1981) developed type 1 diabetes at age 11.
She was the daughter of Charles Evans Hughes (1862, 1948), a former governor of New York, an associate justice of the Supreme Court of the United States, and a presidential candidate (he was defeated by Woodrow Wilson), among other political accomplishments.
At the time Elizabeth was diagnosed, most people who had untreated type 1 diabetes only lived about a year after diagnosis.
In addition, most treatments included a starvation diet.
Elizabeth was put on such a diet, going from around 75 pounds (34 kilograms) to 45 (20.4 kilograms) in three years.
Eventually, Frederick Banting agreed to take Elizabeth on as a private patient.
Determined to get well even though the disease was destroying her health, she became one of the first patients treated with the “new” medication for diabetes, insulin.
She recovered quickly and was eating a normal diet within two weeks. (For more about Banting and insulin, see above.)
Who was Leonard Thompson?
In January 1921, Leonard Thompson (1908, 1935) was the first person with type 1 diabetes to receive an injection of insulin.
He was 14 years old at the time and weighed a mere 65 pounds (27 kilograms).
The insulin was created by Macleod, Banting, and Best (see above) and was reported to be “a murky, light brown liquid containing much sediment,” a far cry from what insulin is like today.
Thompson had an allergic reaction to the first shot.
But after James Collip (1892, 1965) removed many of the contaminants, the cattle-extracted solution was successful, resulting in Thompson’s sugar levels returning to “normal.” Thompson would continue taking insulin for the rest of his life.
He died at age 27 of pneumonia, thought to be a complication from his diabetes.
Why was it so difficult to make insulin long ago?
Overall, insulin was difficult to manufacture in large quantities, and there was also a problem with contamination of the insulin. In addition, at that time, there were about one million Americans with type 1 diabetes. Not only was there a low quantity and quality of insulin, there were also problems matching a correct dosage to a person.
Which company made the first commercial insulin?
The company responsible for making the first commercial insulin was Eli Lilly. In 1922, in collaboration with MacLeod, Banting, Best, and Collip (who realized they could not commercially produce their insulin in large quantities), the company put the new drug through more than 100,000 tests. By April 1923, the company was producing more than 180,000 units of insulin per week, although the overall preparations were difficult (they used cattle and porcine pancreas glands).
Who was the first person to crystallize (purify) insulin?
Because the first human insulin preparations were so impure, there was a need to isolate a pure form of the hormone. The first person to develop such a pure insulin, also called crystallized insulin, was American biochemist John Jacob Abel (1857, 1938) in 1926. Abel was also the first person to purify adrenaline (originally discovered by Edward Sharpey-Schäfer; see above), a substance he called epinephrine, and first to invent a primitive artificial kidney.
Who was Sir Harold Himsworth?
Sir Harold Percival Himsworth (1905, 1993) is thought by many historians to be the first to describe diabetes as a syndrome. Other earlier physicians had mentioned the possible connection between late-onset diabetes and obesity, hypertension, and arterial diseases. But Himsworth was the first to mention the syndrome in his 1949 Lancet paper “The syndrome of diabetes mellitus and its causes.”
American pharmacologist John Jacob Abel was the first scientist to purify insulin.
Who was Elliot Joslin?
Elliot Joslin (1869, 1962) is credited as one of the first diabetes researchers to uncover the association between obesity and diabetes and one of the first physicians to specialize in diabetes.
In addition, in the 1930s, he was the first to note the association between diabetes, hypertension, and arterial disease.
He was the founder of the Joslin Institute, a premier research institute specializing in diabetes. (For more about the Joslin Institute, see the chapter “Resources, Websites, and Apps.”)
When was the true structure of insulin determined?
The full structure of insulin, called a peptide hormone, was discovered in 1955 by British biochemist Frederick Sanger (1918, 2013). It was the first protein to be fully sequenced (or determining DNA bases in a genome; for more about genomes and DNA, see the chapter “Other Types of Diabetes”). Sanger won the Nobel Prize in Chemistry in 1958 for his research on insulin (he also won a Nobel Prize in Chemistry in 1980, one of only two people ever to have done so in the same category).
What were the steps to developing synthetic insulin?
Research shows that once a protein’s sequence is known, it is possible (in theory) to make the same thing synthetically.
Thus, in 1963, insulin was the first protein to be chemically synthesized in the laboratory.
But it was still difficult to produce enough of the insulin for the million or more people with diabetes.
By 1978, insulin became the first human protein to be manufactured through biotechnology.
It was first synthesized by American geneticist Arthur Riggs (1939, ) and Japanese molecular biologist and chemist Keiichi Itakura (1942, ) using E. coli bacteria with recombinant DNA technology.
The City of Hope National Medical Center (to date, Keiichi Itakura still works at the center), along with the biotechnology company Genentech, synthesized the first human insulin in a process that could produce insulin in large amounts.
In order to do this, the researchers inserted a gene for human insulin into bacterial DNA and used the bacteria as minifactories to make the A and B chains of the protein separately.
Then a chemical process combined them.
This procedure created a more “human-userfriendly” type of insulin, which was much more stable than animal insulin.
Most insulin-dependent people with diabetes now use recombinant human insulin instead of animal insulin.
Why did so many people hide their diabetes diagnosis long ago?
I t is hard to say why so many people once hid their diagnosis of diabetes.
In fact, it was often called an “invisible” disease because most people showed no symptoms, and many chose to hide their condition.
Some of the reason was no doubt cultural (often called the “stiff upper lip” syndrome), and many people with the disease did not want others to know they were not healthy.
Before the availability of insulin, having the disease often meant a quick death.
Other times, because the disease was not well understood, many people did not know whether the disease would spread.
All this, and no doubt more, led people to hide their diagnosis of diabetes.
Through research and education in the last half century, the disease, although still not fully understood, does not have the same stigma as in earlier times.
Before synthetic insulin was invented, pigs like this one had been used to produce insulin for humans with diabetes, since their insulin is quite similar to a person’s.
Which animals were used for insulin in the past?
Long before synthetic insulin was available, insulin for human use was usually derived from animals, especially pigs and cattle.
For example, the amino-acid sequence of pig and human insulin are almost identical, but not exact: pigs’ insulin differs from humans’ by one amino acid, and cattle (bovine) insulin differs by three amino acids.
But in the 1920s, no one knew the details of genetic sequencing.
Thus, the researchers were fortunate that the various animal species’ insulin used were almost the same as in humans (although sometimes there were adverse reactions to the animal-extracted insulin, such as skin rashes).