Little Pharma and Insulin Celebrate a Centenary

"In ancient times and medieval ages diabetes was usually a death sentence. Aretaeus did attempt to treat it but could not give a good outcome. Sushruta (6th century BCE) an Indian healer identified diabetes and classified it as “Madhumeha”. Here the word “madhu” means honey and combined the term means sweet urine. The ancient Indians tested for diabetes by looking at whether ants were attracted to a person's urine. The Korean, Chinese, and Japanese words for diabetes are based on the same ideographs which mean “sugar urine disease."

"In Persia Avicenna (980–1037) provided a detailed account on diabetes mellitus in 'The Canon of Medicine'. He described abnormal appetite and the decline of sexual functions along with sweet urine. He also identified diabetic gangrene. Avicenna was the first to describe diabetes insipidus very precisely. It was much later in the 18th and 19th century that Johann Peter Frank (1745–1821) differentiated between diabetes mellitus and diabetes insipidus."

Dr. Ananya Mandal, clinical pharmacologist, West Bengal

Diabetes Mellitus is an ancient malady and it was without a cure and has remained so throughout human history. The word is derived from both Greek and Latin; a combination of 'diabetes' meaning siphon in Greek and 'mellitus' in Latin whose meaning is honeyed. To pass through honey is how diabetes was described in reference to the sugared content of urine. It was identified through the sugar crystals that formed when urine dried. In diabetes, excess sugar appears in a diabetic's blood and urine. 

James Collip as graduate student, 1914

It was the discovery of insulin in 1921 -- a century ago -- by three researchers at the University of Toronto laboratory of Dr.J.J.R. Macleod -- Drs. Frederick Banting, Charles Best and James Collip -- that gave insulin-dependent diabetics a new lease on life. Before the discovery of insulin and its availability as a protein and hormone that would move glucose/sugar from the blood stream to the body's receptive cells to produce energy, the diagnosis of what was once termed Juvenile Diabetes (now Type 1) was a death sentence.

Without the capacity to utilize the glucose derived from food and drink for energy, the body was slowly starved of the energy it needed to survive. Major organs were affected; the heart and kidneys and the nervous system. Heart failure, kidney failure, diabetic retinopathy and diabetic neuropathy leading to nerve death and gangrene and amputations spelled the future for people with diabetes. The balancing act of blood sugar and insulin, not a cure but a treatment, now grants people with diabetes the opportunity to live normal lives.

It has been mostly young people, children and infants who have suffered from insulin-dependent diabetes; without insulin an agonizingly slow death was inevitable as people's organ functions became degraded and deteriorated. The very act of consuming food created more glucose circulating in the blood, and reducing the amount of food ingested led to starvation; either way an early death ensued. There was no useful protocol or treatment to prolong life.

Insulin-dependent diabetes was theorized to have occurred through a genetically endowed susceptibility, a DNA inheritance triggered by some foreign substance introduced to the body that occasioned an immune response which destroyed the ability of the beta cells in the Islets of Langerhans located in the pancreas to produce insulin. Without insulin, glucose circulating in the blood could not be transferred to the body cells and tissues and muscles and brain to produce energy.

At the present time a chemical analysis with the use of strips placed into a meter to determine the amount of glucose/sugar in urine is a common way of determining how well a diabetic is able to balance his/her insulin injected on a daily basis to reduce excess sugar in their blood to achieve as normal a balance as possible. It is, in essence, a miraculous discovery that millions of people all over the world past and present have reason to be grateful for.

Frederick Banting and Charles Best on the roof of the University of Toronto’s Medical Building in 1922. Dogs were used as experimental subjects in the insulin tests.   Courtesy the C. H. Best Papers, Thomas Fisher Rare Book Library, University of Toronto.

 

"The restoration of this patient to his present state of health is an achievement difficult to record in temperate language. Few recoveries from impending death more dramatic than this have ever been witnessed by a physician", wrote Dr. J.R. Williams in 1921, of his 15-year-old patient-invalid, James Havens Jr., who had been one of the first in the United States to be administered insulin, when he was close to death with Juvenile Diabetes. 

"To think that I'll be leading a normal, healthy existence is beyond all comprehension", wrote fourteen-year-old Elizabeth Hughes in Toronto, having been brought back from the brink of death. "Oh, it is simply too wonderful for words this stuff." Children whose lives had been confined to home because they were too sickly to be out, unable to walk about, before long once on insulin returned to school, healthy and with a new daily routine of insulin injections.

"By Christmas of 1922, I had witnessed so many near resurrections that I realized I was seeing enacted before my very eyes Ezekiel's vision of the valley of dry bones", wrote Elliott Joslin, the doctor who embraced insulin treatment and pioneered its use in the United States, and whose clinic is now recognized worldwide as the leader in diabetes treatment innovation.

Drs. Banting and Best's research leading to the isolation of insulin as a clear, life-giving fluid saving so many lives came hard on the heels of the 1919 Spanish Flu which had wiped out entire families and settlements around the globe. It was an era of polio, measles and rubella surging through the world of children. Cancer was treated mostly with disfiguring surgery that was largely ineffective in stopping the advance of the scourge of fearful death.

In recognition of their great medical advance, Dr. Frederick Banting and his laboratory supervisor, Dr. Macleod were awarded the Nobel Prize for medicine in 1923. Dr. Banting shared his financial portion with Dr. Best and  and Dr. Macleod with Dr. Collip.  Frederick Banting refused to put his name on the patent, considering it unethical for a doctor to profit from a discovery that would save lives. James Collip and Charles Best in turn sold the insulin patient to the University of Toronto for $1.