Professor Mladen Vranić received the honorary degree of the University of Zagreb, Croatia in 2011

I was born in Zagreb in 1930 to Vladimir and Ana (Figure 1), and I grew up as an only child in an environment strongly influenced by the academic pursuits of my father, who was a mathematician. Our home was a gathering place, not only for colleagues of Science, but also for colleagues in the Arts, including actors and musicians. For a young person, it was a wonderful experience and unique to the culture of Zagreb at the time. Even my elementary school was influential, preparing us to fight for originality and for useful stubbornness.
In 1918, my father and his brother changed their name and religion, in order to facilitate joining mainstream life in Croatia. My father completed a doctorate in mathematics and physics and became a private docent. He was considered a very talented scientist, but because of his background, he was told that he would not be able to pursue and academic career. My father became Vice President of an Italian insurance company, but he was also well known in the University Community and continued to give lectures, examinations, and write mathematical books and scientific papers. However, in May 1941, he received a letter from the Rector of the University in Zagreb, which explained that his appointment was being terminated to adhere to the racial laws. The letter stated that he did an important job for the University without any enumeration.

When I was 10 years old, I came home and told my parents that we played an interesting game at school: “Chase the Jews”. This is when my parents explained to me that I was of Jewish background. At the time, this didn’t have any effect on me because I felt that I was never exposed to any anti-Semitism, and our school game reflected more of a harmless game of tag. However, when the Ustase ruled in Croatia, I noticed that there were strange pictures in the newspapers. My father saved those newspapers, and the titles were telling. “Blood and Dignity of the Croatian People are Protected by Special Provisions”, signed by Milovan Zanic and Ante Pavelic (Figure 2). I didn’t yet understand that this was a death sentence for my family and me. In the same newspapers, on May 3, 1941, there was also an article that explained the genetic need for the new racial laws, written by a professor of genetics.

My first year of high school coincided with the fascist Ustase government in Croatia. With my father, mother, and grandmother, I managed to escape in 1941 to Crikvenica, which was under Italian occupation. Sadly, however, most of my other relatives were killed in the extermination camps of the Ustase or the Nazis. In 1942, we spent one year in Italian concentration camps at Kraljevica and Rab, respectively. The prisoners organized a school in the camp, and some of the teachers in these concentration camps actually became University Professors in Zagreb after the war. Following the collapse of Mussolini’s government in Italy in 1943, and because a large part of Croatia was liberated by the Partisans, we were able to escape in January 1944 from the island of Rab to Taranto (Italy), which at that time was occupied by the Allied forces. Our escape was made possible when the last partisan ship carrying wounded partisans also carried us to the island of Vis. For the last year of the war, my father returned to Croatia to join the Partisan movement, while I, my mother and my grandmother stayed in Taranto until the end of the war.

I spent two years of high school in Taranto, and since the education focused mainly on classics, it greatly stimulated my love for literature. We covered, Dante’s Comedia Divina, and I knew a lot of it by heart. Today I only remember Francesca De Rimini’s statement “Amor Cha Nullo Amato Amar Perdona”. I was much luckier than Francesca since I am very fortunate to have a fantastic wife, whose support has always been invaluable, and three daughters, who are great fun. After the war, I returned to Zagreb and completed my final three years of high school. In the meantime, my father became professor and Dean of Economics and later Engineering, and he also lectured on the theory of probability. In addition, my father also brought the first computer to the University of Zagreb, despite the fact that his mathematical colleagues thought that using a computer would be a “prostitution” of math.

I enrolled in the Medical School in Zagreb, where the Department of Physiology had a keen scientific interest in carbohydrate metabolism and diabetes, initiated by Professor Allegretti a few years earlier. This early summer, scientific experience in Zagreb was further enhanced by my participation in two summer research programmes at the Universities of Vienna and Amsterdam. The only experience I had as a practicing physician was during internship and one year of military service, and since it would have been very difficult to combine clinical practice with basic research, I decided to embark on a career as a physiologist. During summers and later, as a research assistant, a close collaboration developed with Drs. Allegretti (Chairman of the Department), Pokrajac, Rabadija and Mihic. In addition, we had intense discussions with respect to teaching and research with Fister, Gabric, Ris, Nakic, Kastelan, and Silobrcic (Figures 3, 4, 5). The intense teaching of general physiology provided a background for the rest of my career, and it was a critical early experience.

My Ph.D. thesis discussed the growth of pancreatic islets by cortisol, providing early evidence that new islet cells sprout from ducts. I presented this work when I arrived in Toronto, and my post-doctoral supervisor (the co-discoverer of insulin, Dr. Charles Best), was extremely enthusiastic, which was of great importance for my initial career. It was marvelous how Professor Best stimulated young researchers.

When completing my Ph.D thesis, I felt that I needed post-doctoral training, and a well-known German professor of Diabetology, Werner Creutzfeld, whose father co-discovered “mad-cow disease”, helped me many years earlier. He introduced me to Otto and Anna Sirek, from the University of Toronto, and after exchanging a few dramatic letters, Dr. Best invited me to be his last post-doctoral Fellow (Figures 6, 7). I got a passport from the Ministry of Anterior, who felt that my late-wife, Magda, and two-year old daughter Iva, would have to remain behind. Fortunately, my mother had a spa in Zagreb, and one of her patrons was Savka Dabevic. Luckily Savka supported us, and so my Canadian adventure started.

In Toronto, I got very interested in sophisticated research in the field of Diabetes and I felt that in order to continue, it would be advantageous to stay in Canada, at least for a while. Savka was disappointed, but when she later experienced her own troubles, she understood my decision much better. Three years after arriving in Canada, we returned to Zagreb for a visit. It was an incredibly emotional moment. I realized that when I was living in Croatia, I took for granted the beauty of its cities, Dalmatian coast, and its mountains. My love was for the incomparable rock-climbing in Slovenia. When visiting Croatia, there was some resentment from my colleagues because I had left the country. However, from the beginning, I had a close relationship to the Vuk Vrhovac Institute of Diabetes, which can be credited to Professor Skrabalo (Figure 8). This resulted in collaboration, regular visits to Zagreb, and participation at many symposia; some of which we organized together.  I was also well supported by Granic, later by Metelko, and other diabetologists throughout Croatia.
My relationship to the University of Zagreb has always remained important, and this has resulted in many collaborations and long lasting friendships. I was very honoured to be one of the first three Croatian Scientists, who became visiting professors. In 1989, we organized an international meeting between Zagreb, Toronto, Stockholm, and Boston, where in addition to all Croatian diabetologists, we also had Dr. Luft, Chair of the Nobel Committee, its secretary, and a number of additional scientists. From 1991 to 1993 I organized visits from the Rector, and many professors from the University of Zagreb, which was helpful to inform the Canadian public about the situation in Croatia (during Domovinski Rat). I was especially honoured when I became a corresponding member of the Croatian Academy of Arts and Science. I was very honoured when I received a diploma for the promotion of Croatian medicine and public health from the Croatian Medical Council. Dr. Janko Herak included aspects of my life and science in the book Distinguished Croatian Scientists in the World. I have given many lectures throughout Croatia, and I am a member of the International Committee for Medical Studies in English, in Zagreb. For many years I have promoted the relationship between the Universities of Toronto and Zagreb. This coincided with my title as Honourary President of Toronto AMCA.
In terms of my research, I participated in a number of areas in Diabetes research, which developed sequentially, like a story. To understand pathology of Diabetes, it is necessary to measure production of glucose, mainly by the liver, and utilization of glucose, mainly by the muscle, even when the sugar dramatically changes in blood. I was lucky that there were two students who had a background in biophysics. This allowed us to further develop such methods, which were previously not used in clinical research. We modified the methods, validated them, and like a tsunami, clinical and basic researchers started to use those methods widely. This provided the basis for understanding the role of different hormones and their interactions, and how they work in physiology and in Diabetes. The breakthrough occurred when I was invited by the Kroc Foundation in California to organize the first Symposium on Exercise and Diabetes. In a fantastic environment, a group of 25 scientists intensified work in this field, which was followed by a number of symposia. Today we know that exercise cannot only improve diabetes, but it can also prevent the onset of type 2 diabetes. There was a dramatic improvement for diabetics after we and others classified the problems related to exercise and diabetes, so that today, even diabetic patients can become Olympians. With clinical researchers, we also classified the effects of some lipid diseases.
However, the question still remained; why could exercise prevent diabetes? Most recently, in a series of papers, we hypothesize that exercise affects the hypothalamic-pituitary-adrenal axis and the release of cortisol. It increases glucose utilization by the muscle, and decreases inflammation. All of these factors decrease oxidative stress, and protect the islet cells in the pancreas from deteriorating. This work combines tracer, biochemical, and molecular methods, and it was only possible through wide collaboration with specialists in different areas. In addition, we now know that repeated stress can deteriorate diabetes and perhaps even induce diabetes. Very much to our surprise and to that of clinicians, we showed that if animals can adapt to repetitive stress, they could actually prevent the onset of diabetes, as is the case with exercise. This concept of adaptation to stress carries implications for many diseases.
Diabetes is such a dangerous disease, because it can affect many organs. This is because increased blood-sugar enters the cells and affects the structure of many proteins. We demonstrated a mechanism, whereby both the liver and the muscle are protected against high blood sugar, and thus, they are also protected against major complications.
The general belief concerning the endocrinology of the pancreas was that insulin and glucagon (its two main hormones) were only produced in the pancreas. In experiments that we conducted both in Toronto and during my sabbatical in Geneva, we demonstrated in dogs, that the stomach can produce equal amounts of glucagon as the pancreas. This was a very dramatic finding, because it changed a scientific dogma. It not only explained the role of glucagon in diabetes, but it was also very helpful in understanding the interrelationships of the effects of insulin and glucagon.
In the last twenty years, it became clear that improved blood sugar control decreases the danger of diabetic complications. This is called, intensive insulin treatment.  However, the problem is that this results more frequently in episodes of low blood sugar, which complicates a diabetic’s life. It can be lethal and damage the brain, since this is dependent on a normal supply of blood sugar. We studied why low blood sugar occurs using molecular methods to study changes of genetic activities in the brain, and we patented a new method to prevent low blood sugar. The experiments are still being conducted in rats until every aspect is sufficiently safe to start experimenting in humans.
In terms of my successes, my greatest pleasure and pride has been that some of my graduate students and post-docs are leaders in their own fields today. For example, they have been Presidents of the American Diabetes Association, Japanese Diabetes Association, and the European Association for Studying Diabetes.
In addition to my own research and teaching, I have been involved in administrative work as a Chair, or as a member of various committees organizing symposia. I am proud that during my Chairmanship of the Department of Physiology, I brought together clinicians and basic scientists for collaboration. I have also worked for many granting agencies and journals as an Associate Editor. I am extremely proud for being a member of four academies, having four honourary degrees, receiving the two highest Canadian Civilian Awards, and for being the only Canadian who has received Key recognitions in Diabetes, with respect to science and training of future scientists.
The great American Poet Robert Frost wrote in his famous piece “The Road Not Taken” captured what I have seen so many successful people do.  He writes:-

Indeed, all of us are always facing major choices.  I attempted to take the road “less traveled”.  That is the route to originality, which in my opinion is the key to making a difference in any discipline or any profession.
Life can be unfair and it can be tough.  It is not easy, to get new and original ideas accepted, and it is a constant fight to get grants, and to get papers and new ideas accepted in competitive journals.  In that respect, I titled a recent retrospective “Odyssey between Scylla and Charybdis through storms of carbohydrate metabolism and diabetes”.  You may recall that Scylla and Charybdis were two sea monsters in Greek mythology described by Homer. They were located close enough to each other that they posed an inescapable threat to passing sailors, including Odysseus. Avoiding Charybdis meant passing too close to Scylla and vice versa. 

Life is full of such challenges.  It may sometimes feel as if you need the legendary strength and perseverance of Odysseus to avoid being devoured by sea monsters.  But you can and must persevere.

In the end, my thanks go to my wife Linda (Figure 9), since without her love and support, it would be impossible to get through all of life’s challenges and the stresses of immigration. My daughters, Iva, Anne, and Claire (Figure 10) are all very successful in their own endeavors, but in my dreams, I still see them as little girls who have enchanted me with their fun.