Dr. Sam Seifter: Reflections on His Days at Einstein; My Recollections and His Contributions

Olga Blumenfeld1

1Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461

Sam Seifter, Distinguished University 
Professor Emeritus
Sam Seifter, Distinguished University Professor Emeritus

I first met Sam Seifter and Paul Gallop in 1960, at a Gordon Conference on Proteins and Nucleic Acids. After several talking sessions, I was offered a postdoctoral position in Paul’s lab. Sam was one of the first faculty members at this newly established College of Medicine and Paul had joined him as a member of the Department of Biochemistry. Paul had set up his own lab, part of the Unit for Research in Aging headed by Chip Deming, in the basement of Van Etten Hospital. Sam’s lab was in the Forchheimer building, but their research interests were closely tied. The two men were collaborating on several projects, but above all, they were close friends, two beings sharing the same thoughts and values. I was lucky to join them, to become a member of their circle, and to have them as teachers, mentors, role models, colleagues, and friends.

At that time, Sam’s and Paul’s interests focused on colla- gen, a major insoluble extracellular protein about which little was known. They used ingenious approaches to study its properties and structure in solution, including the mechanism of fiber formation through covalent cross-linking. In attempts to solubilize collagen, Sam shifted his attention to a bacterial collagenase, that of Clostridium histolyticum. He purified the enzyme, stud- ied its properties, and showed that it is specific for col- lagen, giving rise to well-defined peptides. This led to the understanding of amino acid requirements for pep- tide cleavage and, indirectly, shed light on the unusual features of the amino acid sequence of collagens. At the time, this was a big step forward in understanding the structural features of collagen. Carl Franzblau and Elvin Harper participated in these studies as students and along with Shizuko Takahashi, who later joined the lab as a postdoctoral fellow, they contributed much to the detailed knowledge of the structure of this enzyme, its metal requirements and its elastolytic activ- ity. Because of these seminal contributions, Sam’s name remains associated with this enzyme. With Mercedes Paz, who joined the lab as a postdoctoral fellow, they began to study the nature and mechanism of covalent cross-linking in elastin, another major protein of the connective tissue.

Other important contributions included development of new methods, many ingenious, such as determination of galactose in proteins by use of galactose oxidase or the determination of aldehydes in proteins by use of tritiated sodium borohydride.

In the early 1970s, Sam and Paul were asked to write a review on the structure and metabolism of connective tissue proteins, for Annual Reviews of Biochemistry. The knowledge in that field was growing and the discover- ies of Partridge in England and those from Sam’s, Paul’s, and Carl Franzblau’s labs at Einstein were leading to a general excitement about the elegant chemistry that involved covalent cross-links resulting in the formation of fibers of collagen and elastin. The review became an important undertaking for Sam, and he devoted much time and energy to it. That review remains a classic about the state of knowledge at the time and is a testimony to Sam’s clear thinking and precise writing style. Over the years, his other reviews were equally important and each had an impact on their respective fields. Notably, the chapters “Energy Metabolism” and “Carbohydrate Metabolism,” both co-authored with Sasha Englard and published in the books The Liver and Diabetes Mellitus: Theory and Practice, respectively, still remain classic learning tools for the details of carbohydrate metabolism.

Sam’s association with the newly formed Liver Center resulted in studies of murine schistosomiasis as a model for liver fibrosis. With Marcos Rojkind, Michael Dunn, and others, they showed the role of collagen and tissue collagenases in the fibrotic process.

In the early 1970s, Paul and Mercedes left for Harvard and I set up my own laboratory to study membrane proteins, in particular, the structural polymorphisms of glycophorins. Soon after, Sam put together a Program Project Grant, which became funded by the NIH Aging Institute. The grant dealt with the biochemistry of aging and life span of cultured human primary cells. Sam’s lab continued to focus on properties of collage- nase and collagen post-translational modifications, such as phosphorylation of hydroxylysines with his student George Wu. Shizuko Takahashi undertook studies of the gamma glutamyl cycle in relation to the aging of human fibroblasts in culture.

At the same time, to optimize collaborations and activities of the Program Project Grant, a portion of Sam’s lab and my lab were moved to an adjoining space on the 3rd floor of the Forchheimer building. With Tom Robinson and Mahboubeh Egbahli, a postdoctoral fellow, we initiated studies on structural aspects of collagen and elastin in the heart and on the role of cardiac cells, myocytes and fibroblasts in collagen synthesis and degradation. With Maria Zeydel and with help from Bea Wittenberg, we developed methods to obtain pure preparations of either cell type and showed that collagen synthesis was carried out uniquely by the fibroblasts. Our focus on heart fibroblasts and the demonstration of their relatively large numbers and their role in the heart were novel and drew attention within the field.

Sam’s contribution to research was not only in the success of the above projects. His willingness and ability to offer advice optimized the progress of research of many of his colleagues and students throughout the College. His breadth of knowledge, his familiarity with other disciplines, such as physiology or medicine, his ability to understand any experiment, and his creativity, intuition, and perspective made his advice invaluable. In fact, the door to his office was always open and many sought his help in research, personal, or school problems. In addition, he spent many hours editing the manuscripts, presentations, and grants of his colleagues. An excellent example of this aspect of his contributions was the beginning and development of the hemoglobin A1C story in Paul’s and Helen Ranney’s lab in the Aging Unit. Sam’s involvement helped dem- onstrate, at first, that hemoglobin A1C was a hexose derivative of hemoglobin and that it could be relevant to the diabetic state.

Perhaps more important than his contribution to research, was Sam’s contribution to teaching. He was one of the best teachers we ever had and could teach the entire medical biochemistry course with ease and without notes. He could also teach organic or analytical chemistry, physiology, histology, and certain topics in medicine. His knowledge of biochemical pathways and processes was so broad and thorough that it seemed nearly intuitive. Over the years, he organized the medical biochemistry course in which he taught carbohydrate and nitrogen metabolism, he organized and taught a course on the biochemistry of disease, and he organized and taught, nearly single-handedly, the summer biochemistry pre-course for incoming students. He was always involved in tutoring of individual students, and more recently, led tutoring sessions for first year medical students. His lectures not only conveyed information, but were inspiring; he was able to communicate to the students the beauty of the pathways and their importance. It was also apparent how much he enjoyed teaching and how much he cared. He was elected as an honorary member of Alpha Omega Alpha (the medical honor society), was awarded the Sam Rosen Teacher Award at AECOM, and a Continuing Annual Teaching Award was established in his name at Downstate Medical School in Brooklyn.

Sam’s knowledge is also encyclopedic outside of science: music, flowers, stamps, architecture, history, literature, and politics. I was always surprised at the ease with which he could handle the most esoteric questions on essentially any topic. His collection of flowers is a testimony to his patience and his love and respect for nature and beautiful things. With Shizouki, he spent many hours preserving and cataloguing their vast collection of specimens. He also has an important collection of stamps, of which he is very proud and which, I believe, is outstanding.

Another aspect of Sam’s contributions and achievements is his involvement in administrative functions and social issues at the school. He was here from the beginning of the College and was one of the first members of the Department of Biochemistry. I am sure he was quite instrumental in the “setting up” of the department, advising Dr. White, the chairman, in the selection of faculty, design of courses, and teaching. As the school was growing, his friendship with Drs. Lawson and Scharrer and other chairmen probably helped in formation of other basic science departments. In 1976, he became chairman of the Department of Biochemistry and helped it grow and prosper. At a time when pressure from the administration was to integrate the department under the aegis of the Division of Biology, he was determined and succeeded in keeping the department intact as a separate entity.

His involvement and achievements in social issues at the school are many. He was instrumental in formation of the Faculty and Student Senate and in drawing up its rules and regulations. He played a major role in the establishment of the King-Kennedy Program for recruitment of minority students to the school. He actively participated in the design of the program; he tutored students and taught classes and had personal contact with each student. He was honored for his contributions by the Annual Endowed Lecture on Minority Issues and endowed by one of the former King-Kennedy students.

The Einstein’s Quarterly (now known as the Einstein Journal of Biology and Medicine) was his idea and his “pride and joy.” He strongly felt that Einstein’s faculty, students, and alumni needed a forum that could be identified with them and where they could express their ideas, present reports of original investigations, and share poems, prose, or essays. He organized the journal, obtained funding, and edited most pieces. His enthusiasm and the standards of excellence that he designed for the journal were largely responsible for its quality and high regard over the years.

He was a strong advocate for women faculty and students and in the early 1970s helped organize the Women’s Committee of the Senate and develop the Faculty Review Committee. He fought for increases in salaries for female faculty to equalize with those of men and he succeeded. In the Senate he raised many issues having to do with injustice and prejudice and was never afraid to talk or act. He is a leader and a force that made a difference.

Thinking about Sam and our days here, while writing these recollections, I am overwhelmed by feelings: feelings of gratitude – because Sam is my best friend, my most influential teacher and mentor, someone who always encouraged me and believed in me. He guided me when decisions were difficult and helped me “get it right.” He helped with ideas, edited my writing, comforted me when I was sad, and rejoiced with me when “things” were good.

Over all these years, our interactions evolved and ripened. While always a friend, at first Sam was the teacher and mentor; he always remained and still is my teacher and mentor, but then he became a colleague: a serious and real collaborator in research, and a guide and partner in teaching. The joy I feel is the good times we had and shared; the pleasure we shared in good and “elegant” experiments, when grants got funded and manuscripts accepted, the pride and happiness we felt when the students “got it,” the laughter, and the Christmas poems and plays. It was much fun and Sam’s good humor and cheer prevailed. In sad events his favorite saying was “it will pass."

We became even closer over the last few years, when we stopped teaching, doing research, and being “active faculty.” Fortunately, and thanks to Vern Schramm and the Biochemistry faculty, we stayed in our department, in our offices, and Sasha Englard’s office remained in close proximity. With Maurice Rapport, we became the “elders,” our role more as examples, consultants, and friends, rather than active members. We have more time to reflect, to talk, to discuss our respective projects and other topics in science, issues in the world and those raised in the New York Times. Our lunches are well known gatherings and discussions are always lively and much fun.

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