Dr. Stefan Fajans, Active Professor Emeritus of Internal Medicine at the University of Michigan, Division of Metabolism, Endocrinology, and Diabetes (MEND), is an international leader in the study and treatment of diabetes. Dr. Fajans’ long and impressive career spans over seven decades. Although he has been officially retired for 25 years, he still plays an active role in the MEND Division by continuing his fascinating research.
Stefan Fajans was born in Munich, Germany in 1918, the son of Polish parents. His father, Kasimir Fajans was Professor of Physical Chemistry and Director of an Institute of Physical Chemistry established for him by the Rockefeller Foundation in Munich. He was a pioneer in the science of radioactivity. Stefan’s mother, Salomea Fajans was a physician. Kasimir Fajans lost his positions in 1934 by edict of the Nazi regime. The family left Munich in January, 1936, and in September came to the University of Michigan where Professor Fajans had been recruited by Dean Kraus.
Stefan Fajans enrolled in the University of Michigan and received a Bachelor degree in Chemistry in two years. Thereafter, he entered the University of Michigan Medical School and graduated with an MD degree in 1942. He completed a one year internship in New York’s Mt. Sinai Hospital. In 1943 he entered the US Army Medical Corp during World War II. He was assigned to an evacuation hospital which was the first to arrive on Omaha Beach on the third day of the Normandy invasion.
Following the end of the war, Fajans returned to the University of Michigan in 1946 as a research assistant to Dr. J.W. Conn until 1947. He went on to finish his medical residency in 1949, a fellowship in Endocrinology & Metabolism in 1951, and then accepted an Assistant Professorship in that Division. Since that time, Fajans has devoted his life to endocrinology and metabolism research, patient care, and teaching.
In 1949 Fajans initiated a long-term study on the prediction of future diabetes, the natural history of diabetes, its genetics and treatment. This study was funded by two NIH-supported research grants, each of approximately 30 years’ duration and he has continued to be funded to the present time by the NIH-supported Michigan Diabetes Research and Training Center which he obtained in 1977. The study started by the examination and testing by oral glucose tolerance tests (OGTT) and cortisone-glucose tolerance tests (CGTT) of first degree relatives of known diabetic patients, including children. A large group of healthy subjects without a family history of diabetes or large babies at birth served as controls. From these studies evolved in the 1950s criteria for the interpretation of the OGTT and CGTT and a classification of diabetes into four stages (prediabetes, subclinical diabetes, latent diabetes and overt diabetes) as well as the diagnosis and natural history of progression of diabetes. In 1960 a paper for a definition of the ‘prediabetic state’ defined it as the period of time from conception to the first recognizable abnormality in carbohydrate metabolism in a genetically predisposed individual. The paper emphasized that prediabetes was a concept but that a diagnosis of prediabetes could not be made as we had no means of recognizing a genetic predisposition.
A completely new and startling finding was that mild, asymptomatic diabetes was found in children, adolescents, and young adults resembling type 2 diabetes that at that time was thought to occur only in middle-aged and older “maturity-onset type” diabetes patients. Fajans also noted that this type of diabetes occurred in a familial fashion and named it “maturity-onset type diabetes of the young”, later abbreviated as “MODY”. Together with a research fellow from Great Britain, Robert Tattersall, they studied 23 multi-generational families and determined that their diabetes was inherited in an autosominal-dominant fashion, meaning that the disease appeared in approximately 50 percent of each successive generation. One such family with more than 360 members now spanning seven generations and 72 known diabetic patients, the RW pedigree, became a model for further investigation. This inheritance was different than that found in type 1 and type 2 diabetes. This led to the conclusion that diabetes was not a single disease but several different diseases all sharing hyperglycemia. Fajans’ Banting Lecture to the American Diabetes Association in 1978 was entitled “The heterogeneity of diabetes mellitus.”
Simultaneously, in the early 1960s and 1970s, Fajans and collaborators first discovered that amino acids and proteins were powerful stimuli to the secretion of insulin in normal subjects and diabetic patients. Up to that time it was thought that glucose was the only nutrient that caused insulin secretion. These studies were facilitated by the first description of an immunoassay for insulin by Yalow and Berson, and followed by John C. Floyd’s skillfully development of the first immunoassay of insulin at the University of Michigan. This was followed by immunoassays for growth hormone (R. F. Knopf) and glucagon (S. B. Pek) and the demonstration that amino acids were stimuli to the secretion of these hormones.
In 1988 Fajans began collaborating with the molecular geneticist Graeme Bell, PhD, Louis Block Professor of Biochemistry and Molecular Biology and Medicine at the University of Chicago. Fajans co-published the first paper describing a genetic marker for MODY in the RW pedigree in 1991. In 1996, Bell and his colleagues and Fajans found the mutated gene for MODY in the RW pedigree, designated as MODY-1. These studies introduced the concept that MODY is a monogenic disorder while type 1 and type 2 diabetes are polygenic. Studies on the nature and pathogenesis of MODY-1 in the RW pedigree followed with W. H. Herman and other collaborators. Fajans and Bell extended the investigations of MODY by studying families with MODY-2, MODY-3, and MODY-4. Also, 35 years after the introduction of the concept of “prediabetes”, it has become possible to diagnose prediabetes in the RW and other MODY pedigrees as the mutated gene can be recognized at birth. Today at the age of 95 years, Fajans is still studying the RW pedigree as well as other families with MODY. Genetic testing for MODY is routine and can affect correct diagnosis and treatment of diabetes.
Fajans bibliography includes 173 articles in peer-reviewed journals and 72 book chapters.
Aside from his research Fajans was active as the Chief of the Division of Endocrinology and Metabolism and had a reputation as an outstanding and stimulating teacher and practicing clinician. He lectured in and received awards and honorary memberships in the USA and from many countries on all continents. He was president of the American Diabetes Association, 1971-72, and Vice President of the Endocrine Society the preceding year. He gave Banting Memorial Lectures to the Diabetes Associations of the USA, Canada, and Great Britain. In 1983 Fajans was named Russell Lecturer, the most prestigious research award given by the University of Michigan. He is a member of the Institute of Medicine of the National Academy of Sciences.