Cell Death and Differentiation (2005) 12, 1158–1161 & 2005 Nature Publishing Group All rights reserved 1350-9047/05 $30.00 www.nature.com/cdd Interview Early work on the ubiquitin proteasome system, an interview with Avram Hershko A Hershko*,1 Technion. His pivotal work that described the discovery of the ubiquitin system was granted with several prestigious awards, 1 The B. Rappaport Faculty of Medicine and the Rappaport Institute for including the 2000 Albert Lasker Award for Basic Medical Research in the Medical Sciences, Technion-Israel Institute of Technology, Research (with Ciechanover and Varshavsky) and the 2004 Haifa, Israel Nobel Prize for Chemistry (along with Ciechanover and Rose). * Corresponding author: A Hershko, Unit of Biochemistry, the B. Rappaport Faculty of Medicine and the Rappaport Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, 1 Efron Street, P.O. Box 9649, Haifa 31096, Israel. Fax: 9724 853 5773; CDD: How was your family and your early E-mail: [email protected] childhood? I was born on December 31, 1937, in Karcag, Hungary. Cell Death and Differentiation (2005) 12, 1158–1161. Karcag is a small town of around 25 000 inhabitants, about doi:10.1038/sj.cdd.4401709 150 km east of Budapest. It had a Jewish community of nearly 1000 people. My father, Moshe Hershko, was a schoolteacher in the Jewish elementary school in Karcag; most of the Jewish children in that town were his students. His former students from Hungary, and later from Israel, described him with admiration as an inspiring teacher and a role model educator. My mother Shoshana/Margit (‘Manci’) was an educated and musically gifted woman. She gave some English and piano lessons to children in Karcag. My older brother, Chaim, was born in 1936, less than 2 years before me. My mother wanted very much to have also a girl baby, but the times were at the eve of World War II, Hitler’s screams could be frequently heard on the radio, my parents became apprehensive of the future and thus did not try to have more children. Still, my recollections of my early childhood are of very happy times, with loving and supporting parents, growing up in a nice house with a beautiful garden, created by my father who was also an amateur (but avid) gardener. This early paradise was lost rapidly and brutally. World War II broke out, and soon Hungary joined in as an ally of Nazi Germany. In 1942, my father was taken by the Hungarian Army to serve as a forced laborer, with companies of other Jewish men. They were sent to the Russian front, where most About the author of them perished. Luckily for my father, the Soviet Army Avram Hershko was one of the discoverers of the non- advanced so rapidly after Stalingrad that he was captured by lysosomal ubiquitin proteolytic system. His early work was the Soviets before the Nazis could kill him. Then, he was used dedicated to the biochemistry of the system and the role of by the Soviets as a forced laborer. He was released only in 1946, non-lysosomal protein degradation. Now the system has so we did not know for 4 years whether or not he was alive. grown to become a large family of related proteins with a In the spring of 1944, Hungary’s dictator Horthy understood broad array of cellular functions and important therapeutical that Germany was loosing the war, and planned to desert. The potential. However, how did it all begin? What triggered his Germans sensed this and quickly occupied Hungary. This scientific interest in this field from his previous work? Here, was followed by the rapid extermination of much of the Jewish Cell Death and Differentiation asks Avram Hershko about his population of Hungary. In May–June 1944, most Jewish early work on the system. This interview was obtained thanks people were concentrated in ghettos and then transported to to the kind help of the Nobel Foundation in Stockholm, http:// death camps in Poland. I was 6 years old at that time. We were www.nobelprize.org (r The Nobel Foundation 2004). in a ghetto at the outskirts of Karcag for a couple of weeks and Avram Hershko was born in Karcag (Hungary) in 1937. In then were transferred to a terribly crowded ghetto in Szolnok, 1950 he settled in Israel, where he studied medicine at which is a larger city in the same district. From there, Jews Hebrew-Hadassah Medical School in Jerusalem from 1956, from the entire district were transported further on freight- obtaining also his Ph.D. in 1969. Dr. Hershko worked several trains. They were told that they were sent to work, but after the years in San Francisco before returning to Israel at the war we learned that most of the trains were headed for Interview A Hershko 1159 Auschwitz. By some random event, my family and I were put and he sneaked biochemistry into his lectures on organic on one of the few trains that headed for Austria, where Jews chemistry whenever he could, which was often. Basic were actually used for labor. This group included my mother biochemistry was taught by Shlomo Hestrin, also an inspiring with us two children, my paternal grandparents and my three teacher who had a special talent to transfer his enthusiasm of aunts. In Austria we were in a small village near Vienna, where science to the students. Physiological chemistry was taught adults worked in the fields and in a factory. We were liberated by Ernst Wertheimer, a professor of German Jewish origin by the Soviet Army on the spring of 1945. My maternal whom we had some difficulty to understand because of his grandparents perished in the Holocaust, along with 360 000 heavy German accent, but who had an excellent perspective Hungarian Jews and almost two-thirds of the Jewish people of of integration of metabolism at the level of the total body and of Karcag. Following our reunion with my father in 1946, the physiological contexts of biochemistry. Another part of the family lived for 3 years in Budapest, where my father found job same course was taught by Jacob Mager. Mager was an as a schoolteacher. The family immigrated to Israel in 1950. outstanding biochemist and a man of encyclopedic knowl- In Israel we settled in Jerusalem and I started a new and edge. However, he was very shy and quite a bad classroom very different life. Of course, there were initial difficulties of teacher (although an excellent teacher in the laboratory, as I being new immigrants. We had to learn a new language, learned later). Most of his lectures were delivered while he Hebrew. This was not too difficult for children (I was less than was writing whole metabolic pathways on the blackboard, 13 years at that time), but it was more difficult for my parents. without any notes, with his face to the blackboard and his back Still, my father studied Hebrew and soon started to work, directed to the class. Still, I was so much impressed by the again as a schoolteacher. (Later he taught in at a teachers’ depth and breadth of his knowledge of biochemistry that I seminary and authored mathematics textbooks, which were decided to ask Mager to do some research in his laboratory. very popular in Israel). As always, education of their children I started to work in Mager’s laboratory in 1960. At that time, was my parents’ highest priority. Although we were quite poor there was no formal M.D.–Ph. D. program at the Hebrew immigrants at that time, my brother and I were sent to an University, but it was possible to do a year of research expensive private school in Jerusalem. I suspect that most of between the preclinical and the clinical years of medical the salary of my father was spent on our tuition fees. studies. I did that, and although I completed medical studies At school I was received well by the other children. These later on, I already knew by the end of that year that I was going were times of massive immigration to Israel, so a new to do research, rather than clinical practice. I was very immigrant child with a Hungarian accent did not stand out too fortunate to have had Jacob Mager as my mentor and tutor of much (I am told that I still have some Hungarian accent, biochemical research. He was a scientist of incredible scope especially in English, although my Hungarian language is of interests and knowledge. He was interested in every quite poor now). I was a good student, and learned easily subject in biomedicine, he knew almost everything about different subjects, such as mathematics, physics, literature, every subject and he worked simultaneously on 3–4 com- history and even Talmud! That became a problem when I pletely different research projects. This undoubtedly caused finished high school, I was interested in too many subjects, so fragmentation of his contributions to science, but provided his it was difficult for me to decide how to continue. I chose to students with a broad experience in different areas of study medicine, probably by default, because my brother biochemistry in a single, relatively small laboratory. In a Chaim was already a medical student, so I could inherit his period of a few years, I worked with Mager on subjects as books for free! Chaim always wanted to be a physician, and he different as the effects of polyamines on protein synthesis in is now a very well-known hematologist and an authority on vitro, glucose-6-hosphate dehyrogenase deficiency and a iron metabolism.