Contemplating career options as a medical student in the early 1970s, I wanted to choose a field that would put me in the forefront of scientific advances. It was obvious to me that, once DNA sequences of individual genes could be examined and manipulated, Genetics would spearhead medical progress. What was less obvious was whether such a breakthrough was likely to happen in my lifetime. With all the certainty of a 22-year old budding medical scientist, I decided that it was not. Next on the list was Immunology. If we could not lay our hands on the code of life, I figured, specific immunosuppression would at least allow us to replace defective organs without rejection.

How I ended up in Endocrinology is a whole other story. But the two fields I considered and rejected came back to haunt me one winter night in the early nineties. It was the night that I spent correcting the diabetic ketoacidosis that came close to taking the life of 3-year old Marie, who had just been diagnosed with juvenile diabetes. Between discussing lab results and IV orders with the intensive care team, I had occasion to reflect on how my life as a clinician connected with my research interests which, at the time, were in genomic imprinting and its role in foetal growth and in embryonal tumours. Earlier on that day, I remember having had a discussion with Eleanor Colle who was trying to bring to my attention a paper that had just come out in Nature, showing paternal effects in the association of type 1 diabetes with the insulin gene on chromosome 11--a few short kilobases away from IGF2, the very first imprinted human gene to be identified. By daybreak Marie was asking for breakfast and I had decided that I wanted to make myself part of the effort to predict and prevent diabetes. I was going to prove that IGF2, not insulin, was the gene involved in that association. I spent the next five years proving my brilliant hypothesis wrong and, in the process, stumbled upon the role of the thymus in insulin self-tolerance that was to take my research to places I did not know existed. None of that would have happened without Marie, Eleanor, and the wonderful people who make the JDRF a source of inspiration as well as of funding.

Involvement in the genetics of an autoimmune disease inevitably drew me to immunology, a field that I found intimidating and much harder to teach myself than genetics had been. At the beginning I thought that immunologists knew something I did not, a secret that would only be divulged to me if I could, somehow, secure good standing in the fraternity. It took me a while to realize that there was no secret: practitioners of the discipline have simply learned to live with the absence of conventions. In endocrinology and in genetics, rules are refined and expanded-rarely demolished. In immunology the very axioms are tested in every experiment.

I am indebted to Drs. Jacques Ducharme and Harvey Guyda, my early research mentors, for putting up with my(usually misdirected) youthful exuberance; to Dr. Eleanor Colle for dragging me, kicking and screaming, into diabetes research; and to my father Alexandre V. Polychronakos, M.D., philosopher, homme des lettres, and valiant practitioner of interventional radiology decades before the term even existed: for helping me find a place for science in the greater context of life and teaching me how to say: "I don't know."