Dr. Mladen Vranic is a Croatian born Canadian scientist and was the last post-doctoral fellow of Dr. Charles Best, co-discoverer of insulin. Dr. Vranic has made several ground-breaking advances in diabetes research during his five decades of scholarship, and continues to conduct research and mentor students at the Department of Physiology, University of Toronto. He has won numerous awards and has been honoured countless times by organizations around the world. His achievements include: Fellow of the Royal Society of Canada, the Canadian Diabetes Association Inaugural Lifetime Achievement Award, Canadian Medical Hall of Fame laureate, the only Canadian to receive the Banting Medal for Scientific Achievement Award, the Renold Award for mentoring, and his recent appointment to the Order of Canada (Officer) and Order of Ontario. He holds four honourary doctoral science degrees, including one from U of T.
It was a tremendous honour, privilege and delight to interview Dr. Vranic. On behalf of Canadian Diabetes Association UofT (CDAUT), I extend our gratitude to him for sharing his time and personal experiences with us. Below are excerpts from the interview.
Krishana Sankar: Dr. Vranic, could you describe your beginnings in the field of diabetes research?
Dr. Mladen Vranic: I finished [studying] medicine and then I did graduate work at the University of Zagreb. At that time, the Department of Physiology [at Zagreb] was very small and diabetes research was the only topic. [At the same time], my father developed type 2 diabetes.
There were three factors [that led me to diabetes research]. The first factor is curiosity, it was the driving force. Connected to curiosity was originality. The same as in the Arts and Literature, your work is appreciated if you brought something new [to the field]. I always tried to do something that stimulated my curiosity, and I tried to find an answer [to questions]. The last factor was that diabetes offers an incredible number of possibilities in research. It is a disease related to insulin and glucagon, and my friend called it “double-trouble” [meaning] insufficient insulin and too much glucagon. However, I would call it “triple-trouble”. There is another hormone in the pancreas called somatostatin, and we have found that the third “trouble” is related to too much somatostatin.
KS: How did you feel when Dr. Charles Best invited you to work as a post-doctoral fellow in his lab?
MV: For me it was very exciting because I finished my PhD thesis in a theme that was relatively [cutting-edge] at that time. The question was whether beta-cells can arise from ducts of the exocrine pancreas. It was published in Diabetes, which is one of the most visible journals in the field. [Dr. Charles] Best was very impressed with what I did. I was very excited to be invited [here to Canada] to give a seminar and to have [Dr.] Best be very enthusiastic about it.
KS: What would you say are your most important contributions to the field of diabetes research?
MV: When I started [research], in order to understand the pathogenesis of diabetes you had to measure glucose production in the liver separately from glucose utilization in the muscle. The methods that were available in the US and Canada [during those days] had lots of problems and were not validated. I was lucky, I had students with a background in mathematics and we were able to validate and modify the method. Then we actually developed a new method [to measure glucose production separate from utilization]. The [new] method opened the door for further research, and for a number of years everyone used [our] methods. [This led to the identification of] the roles of insulin and glucagon and how they interacted with other hormones.
Then I started in [the field of] exercise because my preceptor Gary Wrenshall, who was a type 1 diabetic, believed in [the beneficial effect of] exercise. He walked every day after three meals. So we began experiments together [testing the effects of exercise on diabetes]. We [tested this in] depancreatized dogs which we put to exercise. The [dogs’] blood sugar skyrocketed instead of improved. This led to the question: when is exercise beneficial and when is it not? We found that if a person is well-controlled by insulin, then exercise is very beneficial. We did a lot of studies explaining under which conditions exercise is beneficial and [under which] it is not. [Due to our developments in the field], I was asked to organize the first symposium on [the theme of] exercise and diabetes. It was [held] in California at the ranch of the Kroc brothers, who were the owners of McDonald’s. They invited 25 people and we would have discussions until midnight. After this [event] a number of symposia were organized; this further pushed this field. [Later on], epidemiologists found that exercise could not only ameliorate but also prevent type 2 diabetes. This, of course, was the big discovery. It was a big surprise to show that adaptation to repetitive stress can also prevent diabetes. [I therefore] concluded that if this adaptation is possible, it is beneficial to have repetitive stress.
This is of critical importance for understanding the acute complication of [insulin treatment in] diabetes, which is hypoglycemia, and we are developing a strategy to prevent it in diabetic patients. One of the most exciting discoveries was demonstrating that one pancreatic hormone, glucagon, can be produced by the stomach. This discovery changed the dogma of [that] time, and was critical [in demonstrating] the role of glucagon in diabetes. Life-threatening complications to diabetes are due to increased uptake of glucose in many organs. [This] explained the mechanisms for why this does not occur in the liver and the muscle. This was crucial for understanding diabetes complications.
KS: What are necessary characteristics for young aspiring scientists to have?
MV: The first thing is [that] you must be original. You also have to be passionate because you have a lot of fights [in your research and career]. You must be curious, and eventually [there is a need to] translate your research into clinical situations.
KS: It has been many years since the discovery of insulin. Do you think there will be a cure for diabetes?
MV: The answer is very simple. A diabetic [person] today is totally different from a diabetic [person] from fifty years ago. The control of blood sugar is infinitely better for both type 1 and type 2 [diabetes]. Since I [entered] the field, at least four new drugs have been developed for treating type 2 diabetes. The latest ones are the GLP-1 analogues and Toronto played a huge role in this due to [work by] Daniel Drucker. This is probably the most important discovery for type 2 diabetes in the last thirty years. In type 1 diabetes the main problem will be to resolve the immunological issues. Children that are prone to diabetes will be vaccinated. I am sure this will eventually be possible. But the greatest hope, not over night, is stem cells. The hope is that [people] will get stem cells from [their] own skin for example so that their body will not react [as though the cells] are foreign. But there are problems [associated with this type of treatment]. [One issue being] that a beta-cell [derived from a stem cell] would be dangerous if it becomes cancerous.
However, longevity of people with diabetes [now] is almost the same as the normal population, once diabetes is properly controlled. Diabetics can participate at Olympics [and do things that non-diabetics do]. So that’s basically the story. It is an optimistic story.
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Acknowledgements: I would like to thank Dr. Vranic for giving me the opportunity to interview him and Alex Chiang for the photograph.
Disclaimer: This interview was conducted in 2014 as part of the blog for the Canadian Diabetes Association UofT Chapter (CDAUT).
Photograph: Dr. Mladen Vranic
Krishana Sankar 