2013 Victor A. McKusick Leadership Award Introduction: Kurt and Rochelle Hirschhorn1

My name is Joel Hirschhorn, and it is my great pleasure to introduce my parents, Kurt and Rochelle Hirschhorn, recipients of the 2013 Victor A. McKusick Leadership Award. I have none of the usual conflicts of interest, but I do note that I received from the recipients extensive financial and emotional support, as well as life itself.Often, these introductions are done by a current or former trainee. I was not my parents’ first trainee, but I was certainly one of the youngest—the joke around the house is that some of my first words were “adenosine deaminase deficiency.”As many of you know, my parents enjoy talking about the achievements of their children and grandchildren but are not as eager to brag about themselves. So, I will do my best to brag on their behalf.This is a joint award, and in addition to being married for over 60 years, my parents have been occasional formal collaborators. A review of their CVs shows that they have copublished papers or chapters in five of the last seven decades; their scientific collaboration in the field of human genetics began in Sweden in 1957, resulting in their first joint paper in Science. Of course, they have much more frequently been informal collaborators with a constant back-and-forth flow of ideas, as I witnessed over the dinner table and as many of you have witnessed at these and other meetings that they have attended together, such as shown here. They have both been members and regular attendees at meetings of The American Society of Human Genetics (ASHG) for over 40 years.This award is named for Victor A. McKusick. Unlike my parents, I did not get the chance to know him, but I do know that his name is synonymous with leadership in many aspects of human genetics and that his impressive legacy remains strong today. Rochelle and Kurt have each been leaders in multiple ways: not only in scientific achievement but also in other significant respects. These include leadership roles in many scientific societies, including ASHG, in leading by example, in pointing out or helping establish new directions for the field of human genetics, and even in being willing to speak out occasionally, or sometimes more than occasionally, about important issues of the day.Kurt was born in Vienna but left under duress as a refugee from the Nazis in 1938, and he eventually made his way 2 years later to Pittsburgh, where he enrolled in the University of Pittsburgh. After he served in the Army during and after World War II, his family moved to New York and he finished college at New York University (NYU). He graduated from NYU Medical School in 1954. Rochelle’s journey was at least geographically shorter: she grew up in Depression-era Brooklyn and then moved to Manhattan, where she graduated from Barnard College in 1953 and from NYU Medical School in 1957.Rochelle has made a number of seminal scientific contributions, particularly in the fields of immunodeficiencies and lysosomal-storage disorders. She discovered the genetic structure of the adenosine deaminase (ADA)-encoding gene, which is mutated in a form of severe combined immunodeficiency, and of the acid-alpha-glucosidase-encoding gene, which is mutated in Pompe disease. She identified and characterized numerous mutations of varying severity in these genes and became an international resource for clinicians treating patients with ADA deficiency. Through careful studies of patients with ADA deficiency, she discovered the key role of deoxyATP in the pathophysiology. She also recognized and described the first example of somatic reversion of a disease-causing mutation in two patients, resulting in a resolution of their disease. Because of this and other observations, she correctly predicted that ADA deficiency would lead the way as a target for gene therapy. Using red cell transfusions, Rochelle also provided the first evidence that enzyme-replacement therapy would be successful in ameliorating ADA deficiency.This body of work has been recognized in a variety of ways. These include being honored as a recipient of the Berson Award and Master Scientist Award from NYU (where she was chief of the Division of Medical Genetics for 24 years), being elected to the Institutes of Medicine and other prestigious societies, and receiving the 2003 Distinguished Alumna Award from her alma mater, Barnard College.Rochelle has led not only by scientific achievement but also by example as a female physician-scientist in an era when there were few such role models and when there was frequent and active opposition to the idea that a woman could or should pursue such a career. When, in 1986, she was elected to the Interurban Clinical Club, founded in 1905 by William Osler, she was its first female member; she shortly thereafter became its first female president. She also had a variety of significant roles in ASHG throughout her career, serving as a visible role model for young geneticists. She has also paid special attention to mentoring female scientists throughout her career.Kurt has also had numerous scientific achievements, beginning notably with signature accomplishments in two different fields. In immunology, he and colleagues described the mixed lymphocyte reaction, which is the basis for human leukocyte antigen matching in transplantation. In human genetics, he was the first to describe, in 1961, a partial deletion of a chromosome in 4p syndrome (also known as Wolf-Hirschhorn syndrome). This discovery was the beginning of an early and sustained use of cytogenetics to identify a wide variety of chromosomal disorders; such an approach is the foundation of prenatal and genetic diagnosis as it is still practiced today.Beyond his scientific achievements, Kurt played a major leadership role in advancing the field of human genetics. In 1968, he founded one of the first Divisions of Medical Genetics at Mount Sinai School of Medicine. In 1977, he became the chairman of the Department of Pediatrics at Mount Sinai, where during his 18 years in that role he continued to stress the importance of genetics in research and in the clinical care of children. Within ASHG, he has been a member and meeting attendee since 1958, served two separate stints on the Board of Directors, was the society president in 1969, and chaired the Awards Committee. Outside of ASHG, Kurt was one of the founders of the American College of Medical Genetics and was also instrumental in helping establish the first Masters-level genetic-counseling program at Sarah Lawrence. He was one of the founders of the Hastings Center (also called the Institute for Society, Ethics, and the Life Sciences) and served on the ethics committee at Mount Sinai for 30 years. With Harry Harris, who was a mentor and colleague to both Kurt and Rochelle, he edited the first 25 volumes of the Advances in Human Genetics.Kurt’s leadership and scientific career have been recognized by a wide variety of awards, including the William Allan Award and Award for Excellence in Human Genetics Education from ASHG, election to the Institute of Medicine, the Colonel Sanders Lifetime Achievement Award from the March of Dimes, and the Howland Award in Pediatrics. Like Rochelle, he has a strong commitment to teaching and mentoring (they have both taught their medical school’s human genetics course). Even now, Kurt spends much of his day giving advice to trainees and faculty alike—and those of you who know my father know how much he enjoys giving advice.In Yiddish, to have “naches” means to have pride and joy in the achievements of others, usually one’s children. Today, my sisters, Melanie and Lisa, our families (Lisa, Bennett, Jane, and Ariel are here also), and I have “reverse naches”—we are proud and happy for the achievements of our parents. And on that note, I present Drs. Rochelle and Kurt Hirschhorn, recipients of the 2013 Victor A. McKusick Leadership Award.