Without insulin, every insulin-dependent diabetic would be having quite a shortened lifespan.
Today, you’re going to learn of the many different people involved in insulin’s progress to its eventual discovery.
In addition, I’m going to go over how it has evolved since its initial mass production efforts.
So, for everyone who uses pharmaceutical insulin, read on to find out all the people you should be thanking!
Paul Langerhans
In 1868, this German pathologist, physiologist, and biologist was remarkable with skin research (1).
So much so that as an undergrad student, he first discovered a new epidermal (skin) cell that, almost 100 years later, was found to be one of the outermost contributing cells to the immune system.
In 1869, he performed pancreatic research that was so explicitly detailed that among the 9 different types of cells he saw, he described 1 of them as a particular “cluster of cells”.
He didn’t comment any further on these cell clusters or their potential functions.
But we’ll get to the one person who did, shortly.
Oscar Minkowski and Joseph Von Mering
In 1889, German scientists, Oscar Minkowski and Joseph von Mering were experimenting with pancreatectomies (surgical removal of the pancreas) on dogs, which they observed led to severe diabetes (2).
Minkowski even implanted a small section of the pancreas into the depancreatized dogs and noticed a pause in hyperglycemia until the implant was taken out or the small bit of the organ discontinued working properly.
They were the first to come up with the theory that the pancreas is responsible for releasing a substance responsible for some type of glucose regulation in the body.
(Getting warm…)
Gustave-Édouard Laguesse
In 1893, this French histopathologist (one who studies microscopic tissue to investigate the cause of disease) was the first to officially name Langerhans’ “cluster of cells” discovery as the “islets of Langerhans”.
He believed that these clusters of cells produced a secretion that played important roles in decreasing the amount of glucose in diabetic urine and for digestion.
He was definitely on the right track!
Eugène Gley
Motivated by Laguesse’s hypothesis, this French histologist decided to test it to see if he could use this islet cell substance to eliminate glucose from the urine in diabetic dogs.
He was able to reduce glycosuria (excess sugar in the urine) in the pancreatectomized animals while reducing and improving other noted diabetic symptoms.
In an interesting twist of events, Gley wrote a report of his findings, sealed it in an envelope, and gave it to the French Society of Biology in 1905 (3).
Under strict orders, the society was not to open the sealed packet until Gley instructed them to do so.
Upon the discovery of insulin in 1921, he then permitted his findings to be opened.
He then believed he was the first person to discover insulin, unbeknownst to the medical community, during the time his experiments were conducted.
Lydia Maria Adams DeWitt
In 1906, this American pathologist observed a cat’s pancreas waste away after tying up its ducts and was able to isolate groups of islet cells (3).
Although given her lack of efficient equipment at the time, she was able to shortly obtain a beneficial, liquid extract from these cells.
She believed this liquid was a substance necessary for controlling carbohydrate metabolism in the body.
(…warmer…)
Sir Edward Albert Sharpey-Schafer
In 1910, this English physiologist and inventor was accredited to be the founder of endocrinology.
Having acknowledged the islets of Langerhans, he was also the first to coin the word “insulin,” originating from the Latin word “insula,” meaning island.
He noted the role insulin plays during the development of diabetes.
Nicolas Paulesco
In 1916, this Romanian physiologist successfully repeated Eugène Gley’s experiment on dogs (4).
Unfortunately, he was enlisted in the Romanian army for the already-in-progress World War I and had to put a pause on his research.
In 1920, Paulesco was able to conduct new experiments and termed the substance he injected in the dogs’ jugular veins “pancrein” (his word for insulin).
In August 1921, he published his results in the Archives Internationales de Physiologie.
(…getting hot…)
Fredrick Banting, John Macleod, Charles Best, E. Clark Noble and James Collip
In November 1920, Dr. Fredrick Banting, an orthopedic surgeon, was able to convince biochemist and physiologist, John Macleod, to allow him to use his labs to conduct research in finding what substance in the pancreas had been recorded to enable some progress among diabetics.
These labs were at the University of Toronto and Macleod gave Dr. Banting 2 lab assistants, he had previously worked with, to assist him with his research.
They were Charles Best and E. Clark Noble.
Banting, Best, and Noble initially followed similar protocols that Gley and Paulsco used with their research on dogs who underwent pancretectomies.
In August 1921, they were able to use a new pancreatic extract.
A couple of the main differences were that this new substance was taken from fetal pancreata with new removal procedures.
As with the pancreatic samples taken years earlier from other researchers, their current samples were riddled with impurities.
Having higher activity levels was one of them. Conventional insulin has a neutral pH balance.
On January 11, 1922, Macleod permitted Banting to use this new extract on a 14-year-old diabetic boy, Leonard Thompson.
He was diagnosed with diabetes in December 1919.
Administration of the extract included 7.5 ml injections in each butt cheek.
The initial experiment was a failure, with only slightly reduced blood glucose and glycosuria noted.
The results were as followed:
Before this initial flop, Macleod had already brought in James Collip to further assist Dr. Banting with getting a better extract.
Collip was a Ph.D. in biochemistry and an assistant professor at the university with his lab.
Since beginning his work with Macleod in December 1921, Collip used isolated insulin from a calf’s pancreas.
On January 19, 1922, Collip made an incredible discovery in that his particular extract had an ingredient that was over 90% active.
With this new extract, he finally achieved isolating the active substance, yet still with impurities but with much higher efficiency and efficacy.
On January 23, 1922, Collip’s new extract was administered to Leonard and it showed immediate clinical improvement with the results as followed:
In May 1922, the active ingredient in this administered therapy was officially labeled “insulin”.
In 1923, the production of this insulin was initiated throughout the world.
And the Nobel Prize was awarded to Banting and Macleod, later that same year, for their discovery of insulin.
Insulin’s Initial Price per Vile
On January 23, 1923, Banting, Best and Collip were awarded the American patents for insulin, which they sold to the University of Toronto for $1, each.
In November 1923, with a new “insulin factory” just built near campus, which enabled increased insulin production, the price of insulin dropped from 5 cents to 2 cents per vile.
Insulin Now: From Cattle and Pigs to Synthetic, Human Forms
Upon the initial trials of finding a viable insulin extract for human use, animal pancreases experimented on were those of dogs and cats, but the Banting crew and eventual insulin manufacturers settled with cattle and pig insulin extracts.
One of the growing side-effects of these extracts, however, was that they induced allergic reactions among a good portion of diabetics.
By the mid-1970s, insulin demand reached new heights where manufacturers needed over 50 million animals per year to satisfy market consumption.
Around that time, “it took 8,000 pounds of pancreas glands from 23,500 animals to make one pound of insulin” (5).
Those shocking numbers just weren’t sustainable and as a result, a more efficient alternative for insulin production began.
And many pharmaceutical organizations were in on this race.
Including Eli Lily, the primary U.S. insulin manufacturer at that time.
However, a small biotechnological entity called, Genentech, was the first to accomplish this feat.
In August 1978, David Goeddel and Dennis Kleid were able to produce a synthetic version of human insulin that was found to not only be as effective as human insulin but also eliminate the allergic effects many diabetics had with the prior animal-based insulin.
In 1982, this new form of insulin received FDA approval, and Genentech and Eli Lilly signed an agreement to produce and sell this synthetic insulin.
The first 2 insulins made from this discovery were Humulin (fast-acting insulin) and NPH (intermediate-acting).
By 1983, these insulins reached their goals of manufacturing efficiency while reaching the diabetic masses in dire need of it.
After years of debate, on March 1, 2023, Eli Lilly made the announcement that they will be dropping the price of their insulin. Finally making it a little bit easier for diabetics with this medical demand (6).
Insulin Discovery Controversy
There have been quite a few disagreements noted on who truly should be recognized as contributing discoverers of insulin (7).
However, the one thing that separates Banting’s team from others’ rudimentary findings was that he and his crew were the first to successfully extract and separate insulin from the islets of Langerhans of the pancreas.
In addition, they were also able to administer it safely with minimal to moderate side effects.
And for those wondering what happened to E. Clark Noble’s notoriety in all of this, please read why no one usually references his contribution to the discovery in this noted reference (8).
In summary, a lost coin toss ended up having Best be Banting’s assistant and not Noble throughout the work leading up to insulin’s discovery.
Keep in mind, Noble’s work was enormously helpful, especially during the following months after insulin’s discovery.
And before synthetic insulin’s official discovery, his work saved an enormous amount of time for Banting and Best to perform their research on this renowned finding.
Collip was understandably furious that the Noble Peace Prize was not shared with his work, having found a more effective insulin extract, as well (9).
Unfortunately, due to the “powers that be,” they concluded that only Banting and Macleod share this official discovery of insulin.
So What Do You Think?
Hopefully, this information has brought some insight into this incredible drug’s origins.
Now that you’re aware of this insulin timeline, were there any actions of any of these individuals that you may have agreed or disagreed with?
Do you think these actions would have sped up or slowed down insulin’s discovery?
Share this post with anyone else who may be interested in how insulin was discovered!
References
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1769627/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4707300/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205949/
- https://www.elsevier.es/en-revista-endocrinologia-nutricion-english-edition–412-articulo-the-discovery-insulin-continued-controversies-S2173509311000614
- https://www.gene.com/stories/cloning-insulin
- https://www.npr.org/2023/03/01/1160339792/eli-lilly-insulin-price
- https://www.elsevier.es/en-revista-endocrinologia-nutricion-english-edition–412-articulo-the-discovery-insulin-continued-controversies-S2173509311000614
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC137361/
- https://physoc.onlinelibrary.wiley.com/doi/abs/10.1113/expphysiol.1989.sp003266