By Hermione Cabie-Santos, MD and Prof. Honor Blanco Cabie
DIABETES (a metabolic condition in which the body has elevated blood sugar levels as a result of insulin deficiency or insulin resistance) was once a death sentence until the first score of the 20th century. It remains among the health challenges the world faces throughout the current pandemic. Thanks to Canadian researchers of the University of Toronto a century ago, this medical scourge has seen the light of hope as the world pays tribute to the perseverance of a group of researchers led by Dr. Frederick Grant Banting, Charles Herbert Best, James Bertram Collip and John James Rickard Macleod.
This year, millions of patients, families and advocacy groups (in Canada and around the world) celebrate the 100th anniversary of this medical miracle.
The discovery raised a welcome reprieve for sufferers from the unforgiving clutches of the fatal medical condition, when the only therapeutic option was adherence to a carbohydrate-restricted, low calorie diet. A well-known approach was the Allen’s diet, coined after the leading Diabetologist at the time, Dr. Frederick Allen.
Patients on Allen’s diet clung to this stringent approach (to the brink of starvation),
a sacrificial solution to diabetic patients who could not process/metabolize glucose (sugar). In the years prior to insulin’s discovery, this approach meant an extension of life for a year or two, at best. A prescription best described as ‘starving a patient so he/she may live.’
However, one fateful night in 1920, a young surgeon from London, Ontario who recently returned from England as a battalion medical officer, was reading himself to sleep when he chanced upon a medical article in the November issue of the journal Surgery, Gynecology and Obstetrics, “The Relation of the Islets of Langerhans to Diabetes with Special Reference to Cases of Pancreatic Lithiasis,” written by American Pathologist Moses Barron.
Years later, in a letter to Dr. F. G. Banting dated February 14, 1923, Barron wrote:
“Although I was quite interested in the study of the pancreas at the time when I
published that article, I did not have the faintest idea or hope that it would at any time
or in any way be sufficiently suggestive to start such an epoch-making investigation
as you have undertaken.
I wish you and your co-workers great success in furthering the refinement of the insulin
and of bringing its manufacture to a stage where it will be within reach of the millions
or more of suffering humanity.”
One may wonder how the discovery team was created.
The team was formed in the most serendipitous circumstances.
Banting initially contemplated on bringing the research idea to Western University through Professor Miller, a Neurophysiologist unfamiliar with research in carbohydrate metabolism. However, facility and funding were relatively scarce at Western and the suggestion to re-direct the research into the laboratory lap of the better-funded University of Toronto took shape.
In November of 1920, Banting pitched his idea to John James Rickard Macleod, a Physiology expert of the University of Toronto.
Macleod, despite his reservations, eventually became instrumental in providing the modest environment for Banting’s research. He was quoted as saying that despite the risks of failure, such investigation “would be of great physiological value.”
Banting’s idea was relatively straightforward.
He was to isolate the internal secretion of the pancreas to relieve glycosuria (a condition of having sugar in the urine). He postulated that by ligating (tying off) the pancreatic ducts of dogs, such action will atrophy (decrease or shrink in size) the organ’s acinar cells that produce digestive juices, eventually isolating the secretion of the Islets of Langerhans cells (the cells thought to produce the internal secretion of the pancreas).
In essence, Banting may have initially believed that glycosuria was the condition to be addressed in diabetes. Further advances in diabetes management unveiled the importance of addressing hyperglycemia (high blood sugar state) which causes glycosuria.
In May 1920, Banting was introduced to Charles Best and Clark Noble, two student assistants employed by Macleod. Both were seniors in the university’s Honour Physiology and Biochemistry course They were to assist Banting in his pancreatic research.
Little did they know that destiny was inviting them to play a pivotal role in the history of medicine.
With a toss of a coin (as legend would have it), Charles Best became Banting’s first laboratory assistant that spring-summer of 1921. A role which entailed sacrifice, long nights in the laboratory, handling of depancreatized dogs, failures coupled with frustration leading to victories.
On July 30, 1921, Banting and Best successfully prepared a pancreatic filtrate, a pink-colored liquid extract of degenerated dog pancreas (still in its impure state) which they injected into the vein of a terrier dog (the first dog to receive the extract). After a series of failed attempts, a third dog (a yellow collie) eventually received the remainder of the extract in August that year. The collie survived with promising results of reduced blood sugar levels.
For the first time, Banting and Best gave the name “Isletin” to their mysterious extract.
In December that year, James Bertram Collip (an active researcher from the University of Alberta, Edmonton) was invited by Banting and Macleod to develop a method of purifying the pancreatic extract using alcohol purification.
Collip’s work in the research demonstrated the restoration of a diabetic animal’s glycogen production in the liver, a function lost or is lacking in diabetes. The animal received an injection of the pancreatic extract and was allowed to consume milk and sugar liberally. The results were promising.
On December 30, 1921, the discovery team presented their findings during the conference of the American Physiological Society, Yale University. Due to the in-depth interrogation of leading Diabetologists and Endocrinologists in attendance, the presentation was regarded by experts as poorly presented. Nevertheless, this event remains an important thread in insulin’s development.
Also in attendance was Dr. George H.A. Clowes who was the Research Director of the US-based pharmaceutical Eli Lilly and Company. This paved the way for Eli Lilly’s collaboration with the discovery team in the production/standardization of insulin for human use.
Suffice to say that Collip’s major contribution in insulin’s discovery was purifying the pancreatic extract where impurities were dissolved while its lifesaving properties were retained.
Collip’s purified animal extract (purer than previous extracts) of insulin allowed Banting and colleagues at the Toronto General Hospital to begin treating patients, with the first injections administered in January 1922. Within weeks, the world heralded the arrival of a miracle.
Leonard Thompson holds the record of being the first diabetic patient, a 14-year old boy, to successfully receive an injection of purified insulin. Diagnosed as a diabetic in 1919, he was in a state of cachexia (wasting of the body), an image of death in a living body. He first received the extract of Banting and Best and, weeks later, the purer version of Collip’s extract, miraculously improving patient outcome and minimizing adverse reactions/infections to previous impurities.
Thompson’s ketonuria disappeared, his blood sugar improved.
The almost-mythical-response marked the successful revival of a human diabetic treated with the internal secretion of the pancreas. The treatment instantly offered hope and optimism to a doomed teenager. Suddenly, a second lease on life.
Countless miracles were witnessed as insulin became available all over the world:
(1) Elizabeth Evans Hughes, Banting’s prize patient (2) James Havens, the first diabetic to receive insulin the in the United States and (3) Dr. Joseph Gilchrist, first patient who received a pancreatic extract by mouth.
In the same breath, Oscar Minkowski, a pathologist at the University of Strassburg (considered the Grandfather of Insulin by Banting), and Nicolae Paulesco (Romanian Physiologist who described the internal secretion of the pancreas which he named pancreine), are scientists forever etched on the road to insulin’s discovery.
In 1923 the Nobel Prize in Physiology or Medicine was awarded to Frederick Grant Banting and John James Rickard Macleod for their discovery of insulin, a major medical breakthrough saving millions of lives to this day. Banting shared his prize with Best, while Macleod shared his with Collip.
Regardless of the Nobel Prize designation and controversy surrounding the body of research, the discovery of insulin rests in the hands of these gentlemen, led by the unwavering vision of Dr. Frederick Banting.
Today, The International Diabetes Federation has reported that 1 out of 10 adults are living with diabetes. The World Health Organization has estimated that more than 95% percent of people with diabetes have Type 2.
This December, the International Diabetes Federation will host a global virtual congress featuring the latest research on diabetes complications and other sessions devoted to the centenary of insulin as well as the IDF Diabetes Atlas 10th Edition.
Diabetes Canada and other advocacy groups (in the US, Europe, around the world) have created Clinical Practice Guidelines and policies, in the fight against diabetes. An expanded armamentarium of therapeutic options have also been developed.
It is upon the next generation of dedicated researchers to advance diabetes therapy and management This generation owes it to the next, to pass the baton of innovation to find a cure.
While insulin is not a cure, it was (and remains to this day) a lifesaver.
A miracle of hope celebrating a century of victory to conquer diabetes.
About the Authors:
Hermione Cabie-Santos is an internationally-trained Physician and a clinical research professional based in Toronto, ON, Canada.
Honor Blanco Cabie, award-winning journalist, holds a master’s degree in Journalism and Media Management from the Asian Institute of Journalism and Communication, Philippines.
He is Editor of The Manila Standard, Philippines.
References:
The Discovery of Insulin by Michael Bliss
Elizabeth Evans Hughes-Surviving Starvation Therapy for Diabetes (Perspectives, The Art of Medicine, 2011)
International Diabetes Federation
Diabetes Canada
American Diabetes Association
World Health Organization