We lost a wonderful colleague and friend with the passing of Dr. Gustav Schonfeld on May 21, 2011. Gus Schonfeld was the Samuel E. Schechter Professor and former head of the Department of Medicine at Washington University School of Medicine in St. Louis, Missouri. He died at the Memorial Sloan-Kettering Cancer Center in New York at age 77. Gus suffered from complications from chronic myelogenous leukeumia while he was on vacation visiting his children.
Gus was born in what was then Munkacs, Hungary, but is now called Mukachevo in the Ukraine. It is reported that when Gus was 10 years old, he and his family were transported to the concentration camp in Auschwitz by cattle car. He and his parents never saw his 7-month-old brother or grandmother afterward. Gus and his father were separated from his mother and spent time at Auschwitz, Warsaw, Dachau, and Muhldorf. A touching and disturbing description of their time in the concentration camps is contained in Gus' Absence of Closure, published in 2009. Gus describes his father getting him a job in the dispensary, which he attributes to saving his life. His father, who was trained as a physician, treated the sick and kept Gus alive by providing him with food. After the war, Gus and his father recuperated in Czechoslovakia and during this time were reunited with his mother, who had also survived Auschwitz. Relatives of Gus in St. Louis were able to get immigration papers to enable them to leave Czechoslovakia and enter the United States. The three of them moved to St. Louis approximately a year after they had been liberated. Gus donated the proceeds of Absence of Closure to the St. Louis Holocaust Museum and Learning Center, to two Hebrew day schools attended by his grandchildren, and to the Washington University School of Medicine.
Gus received his BA degree from Washington University in 1956 and his MD degree from Washington University School of Medicine in 1960. He did an internship (1960–61) and residency in internal medicine (1961–63) at New York University at the Bellevue Medical Center. He returned to St. Louis as Chief Resident at the Jewish Hospital in 1963. Gus then did postgraduate training as a National Institutes of Health Trainee in Endocrinology and Metabolism at Washington University from 1964–66 and entered the US Air Force School of Aerospace Medicine as a Research Flight Medical Officer from 1966–68. Gus returned to St. Louis at the Cochran VA Hospital from 1968–70, and during this time he was an Assistant Professor of Medicine at Washington University and an Assistant Physician at the Barnes Hospital. During this time, he collaborated with David Kipnis on studies of glucose and fatty acid interaction and metabolism. Gus next spent 2 years in the laboratory of Dr. Robert Lees, with appointments at Harvard Medical School and the Massachusetts Institute of Technology Clinical Research Center. He was appointed as an Associate Professor of Metabolism and Nutrition at MIT, and it was here that Gus began his investigations on lipoprotein metabolism.
With Bob Lees and colleagues, Gus published a description of the catabolism of human very low-density lipoprotein and a description of an assay of total plasma apolipoprotein B concentration in human subjects. This assay has taken many years to standardize but has become increasingly important. Gus returned to Washington University as an Associate Professor of Preventive Medicine and of Medicine in 1972 and was promoted to full professor in 1977. During the next 30 years, Gus and his colleagues produced a steady stream of important studies on the structure and metabolism of the plasma lipoproteins. He had a number of outstanding collaborators who became leaders in the field, including Joe Witzum, Wolfgang Patsch, and Anne Goldberg, to name a few. Gus' studies covered a wide range of topics. A number of studies examined assays of specific antibodies to epitopes on the surface of lipoproteins. In this way, Gus and his colleagues were able to gain an understanding of the changes on the surfaces of low-density lipoprotein, high-density lipoprotein, and very low-density lipoprotein that occurred during lipolysis and metabolism. An example is a paper by Schonfeld, Patsch, Pfleger, Witzum, and Weidman entitled “Lipolysis Produces Changes in the Immunoreactivity and Cell Reactivity of Very Low Density Lipoproteins,” published in the Journal of Clinical Investigation in 1979. Gus also performed a number of studies on the effects of hormones on lipoprotein structure and metabolism, in accordance with his interest and training in endocrinology and metabolism. With Patsch, Kim, and Wiest in Endocrinology in 1980, he describes the effects of sex hormones on rat lipoproteins. In addition, Gus investigated the effects of probucol, colestipol, and statins on lipoprotein structure and metabolism, and he was involved in various clinical trials with lovastatin and pravastatin.
I first met Gus in 1972 when he succeeded Dave Kipnis as the head of the Lipid Research Clinic program in Washington University. At the time, I was heading the Lipid Research Clinic program at the Baylor College of Medicine and the Methodist Hospital in Houston, Texas. Joseph Patsch and I collaborated with Wolfgang Patsch and Gus on one publication, “Characterization of Human High Density Lipoproteins by Zonal Ultracentrifugation,” published in the Journal of Biological Chemistry in 1980. Gus later contributed two chapters to a book that I co-edited on Treatment of Severe Dyslipoproteinemia in the Prevention of Coronary Heart Disease entitled “Truncated Forms of Apolipoprotein B and Hypobetalipoproteinemia” and “The Other End of the Spectrum: Hypobetalipoproteinemia.” The 2008 volume of the Transactions of the American Clinical and Climatological Association contains an article on truncated apolipoprotein B and hypobetalipoproteinemia based on his lecture of the previous year. Gus became interested in hypobetalipoproteinemia about 2 decades ago and continued with this interest throughout his career. He identified various mutations of apolipoprotein B and described in collaboration with Talmud, Humphries, and others “a novel truncated apolipoprotein B (apoB55) in a patient with familial hypobetalipoproteinemia and atypical retinitis pigmentosa” in 1992. Gus and his colleagues elucidated the mechanism of hypobetalipoproteinemia with varying lengths of apolipoprotein B. In some cases, the hypobetalipoproteinemia resulted in an increased rate of catabolism of the truncated apolipoprotein B. In other cases, different mechanisms were involved.
In recent years, Gus' work has become increasingly significant as ongoing efforts are made to get levels of low-density lipoprotein cholesterol (LDL-C) lower and lower in patients. Indeed, with current experimental strategies, such as those involving antibodies and inhibitors to proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that plays a major role in cholesterol homeostasis, therapeutic attainment of extremely low levels of LDL-C could occur in the near future. Investigators now look at Gus Schonfeld's work to predict the lowest levels of LDL-C that may be safely obtained. Similarly, researchers studying inhibitors of microsomal triglyceride transfer protein to lower LDL-C used Gus as a consultant to assess the effects of these drugs on steatosis. Gus was a pioneer in investigating the relationship between the synthesis of truncated forms of apolipoprotein B and steatosis.
Gus was a warm, outgoing, lovable individual. This was obvious to all who knew him at the ACCA since joining in 2006. Devoted to his family, his friends, and his profession, he exhibited the highest ethical standards in all that he did. I interacted with Gus and his lovely wife Miriam frequently. Once when my wife Anita and I were visiting St. Louis as part of a Methodist Hospital activity, Gus and Miriam generously devoted a full day of their activities to making sure that we were well entertained in their hometown. We also saw them many times in New York before our move to Weill Cornell in New York. Gus served as a valuable member of the first National Cholesterol Education Program committee. I remember a meeting on high triglycerides and low high-density lipoprotein cholesterol at the National Institutes of Health in 1994 when Gus brought a sense of balance to the discussion at a time when a representative of the Food and Drug Administration and an academic researcher were pushing to get the fibrate class of drugs banned from the market. I recall Gus saying something to the effect of “there's some advantage to having gray hair in these discussions.” Gus' wisdom, as well as his humor, was always appreciated. I remember Gus' great excitement when he was called from a dinner we were attending in New York in 1996 and was informed he had just been appointed chair of medicine at Washington University. What a thrill and delight this was for him, one of the proudest achievements of a remarkable career.
In addition to Gus' lovely and delightful wife Miriam, he is survived by three children: Joshua Schonfeld, Julia Zeuner, and Jeremy Schonfeld. I have enjoyed having some interaction with Jeremy, who organized his own band at an early age and is now an extremely talented musician. We wish Miriam, her children, and her grandchildren well. We share with them in their loss. Gus leaves a lasting legacy in the field of lipoprotein research. He and his accomplishments will long be remembered.