The last scientist ever recruited by Charles Best, the co-discoverer of insulin, is still hard at work in his University of Toronto lab, carrying on his mentor's legacy.
At 79, Mladen Vranic has just patented an important new finding that will help diabetics control their blood sugar by blocking a common peptide hormone.
While most scientists his age have long since retired, Prof. Vranic will fly to New Orleans today to present his findings at the annual meeting of the American Diabetes Association.
"I came here in 1963 and expected to stay for two years. But 46 years later, I am still here," says the professor of medicine and physiology, who has blue eyes, bushy eyebrows and a slow, deliberate manner of speaking. His small stature belies a huge intellect.
In April, Prof. Vranic was inducted into Canada's Medical Hall of Fame, alongside the late Dr. Best, whose leadership and magnetism defined the department for the 36 years he was at its helm.
When Prof. Vranic joined the department in January, 1963, it was more than 40 years after the discovery of insulin - hailed as one of the greatest medical advances of modern times. But Dr. Best was still very much a star.
Prof. Vranic points to an old photo on the wall of him as a young man with a full head of hair standing beside Dr. Best and his wife. "He always had time for people," he recalls. "I would go into his office and show him my research results. He was extremely enthusiastic and supportive."
Prof. Vranic took up his mantle, helping to train more than 50 PhD students and postdoctoral fellows, including his current one, Jessica Yue.
"I have the same excitement about my research as I've always had. I don't give up easily. In fact, I never give up at all," he says.
He helped cement the university's reputation as a global centre for excellence in diabetes research - a reputation that continues today.
Prof. Vranic's life story is almost as dramatic as Dr. Best's. He grew up in Croatia, part of the former Yugoslavia, and at the age of 11 was sent to a concentration camp in the country's south, annexed to Italy during the war, because of his parents' Jewish descent. Conditions in the camp were relatively good, he says, and he was able to go to school and play sports.
However, fearing the arrival of the Germans, the family tried for months to get out. When Italy collapsed in September, 1943, the family escaped in a boat to an island in Yugoslavia protected by American and British soldiers, as well as Yugoslavian partisans. Three weeks later, the Nazis arrived at the original camp where the Vranic family had been, and sent all the inmates to Auschwitz. All but two perished.
A talented student, Prof. Vranic went on to become a doctor in Zagreb, and learned to speak six languages, including English, Italian, French and Russian. While at a conference in Geneva in 1962, he contacted the University of Toronto to inquire about working with Dr. Best, who had been appointed head of U of T's Banting and Best Department of Medical Research, following the death of Frederick Banting in a plane crash in 1941.
It was difficult to secure exit visas to leave Communist Yugoslavia. But Prof. Vranic's mother owned a spa frequented by local authorities, and she managed to win permission for Prof. Vranic, his wife and two-year-old daughter to go to Toronto.
U of T was an exciting place for diabetes researchers. An endless stream of international scientific luminaries paraded in and out of Dr. Best's office, and he received them all graciously, remembers Prof. Vranic.
Just 22 at the time of the famous breakthrough, Dr. Best had been recruited to work as an assistant to Dr. Banting, under the direction of John Macleod, a physiologist from Scotland.
Dr. Best had given up a chance to play professional football and baseball that summer of 1922, agreeing instead to hunker down in a sweltering, under-funded lab. Together, the two young researchers isolated the hormone insulin, which today remains the prime treatment for diabetics, whose bodies don't produce it on their own.
In 1923, Dr. Banting and Dr. Macleod were awarded the Nobel Prize in medicine. Though they pledged to share the honour with Dr. Best, the younger scientist never quite recovered from the disappointment of being excluded from the prestigious prize. He went on to have a fine career, and is credited with the discovery of the enzyme histaminase and the purification of the anticoagulant heparin. Dr. Best also received the Order of Canada, and 18 honorary degrees.
In his early days at U of T, Prof. Vranic established the important role of exercise in the control of blood sugar in diabetics. He identified when the effects of exercise are beneficial, and when they are harmful, and why at certain times exercise should be avoided. (It depends on the person's insulin levels, as well as their sensitivity to insulin, which is variable.)
Low blood sugar - or hypoglycemia - is one of the most serious consequences of diabetes and can cause irritability, loss of consciousness, and even coma. Although the amount of insulin diabetics inject can be calculated based on blood sugar, the calculation is inexact, which is why hypoglycemia is common.
Prof. Vranic helped to improve the methods to measure blood sugar more precisely, opening up this field of research, and making it possible for diabetics to participate in a greater variety of physical activity, and even become Olympians.
He also conducted experiments in dogs and found that glucagon, a hormone that is released when the body needs more sugar in the blood, isn't just produced in a dog's pancreas, but also in the stomach. The discovery helped differentiate the roles of insulin and glucagon in the control of blood sugar in diabetics.
Over the years, Prof. Vranic has authored 300 scholarly papers and book chapters, and picked up just about every award in the field, including one for distinguished service in training other scientists, and an honorary degree from Sweden's Karolinska University.
"There are very few researchers who are so actively involved in research at his age, who display such mental agility and command of the latest scientific literature. He is truly remarkable," says Gary Lewis, a U of T physician and professor, and Canada's Research Chair in Diabetes.
A glass display case down the hall from Prof. Vranic's office, stuffed with books and papers, contains memorabilia from the Banting-Best era, including a set of old scales and a microscope. The university also has the original telegraph Dr. Banting sent Dr. Best upon hearing he had been awarded the Nobel Prize, pledging to share the honour.
One sad footnote in the well-known story is the depression Dr. Best suffered later in life, detailed by his son in a biography he penned about his parents. Dr. Best had to be hospitalized for a time. Though he eventually recovered, he never again returned to a life of science.
Not so for Prof. Vranic, who isn't planning to give up his lab any time soon.