Prof. Avi Ben-Nun (1947-2019)“What furthered me most in life was that I dared to set high goals”, is what Prof. Ben-Nun used to say. He passed away on January 18, 2019, at the age of 72. He earned his master's degree in microbiology, cum laude, from Tel Aviv University in 1974 and his doctorate in immunology under the advice of Prof. Irun Cohen at the Weizmann Institute in 1981. A year later Avi moved to Boston for his postdoctoral studies at the Department of Genetics at Harvard Medical School. In 1984 he returned as a young scientist to the Department of Immunology at the Weizmann Institute. He was appointed Associate Professor in 1993 and received full professorship in 2007.
The science is still alive: papers dedicated to his memory
1. Kaushansky N.,* A. Kaminitz, H. Allouche-Arnon and A. Ben-Nun. 2019. Modulation of MS-like disease by a multi epitope protein is mediated by induction of CD11c+CD11b+Gr1+ myeloid-derived dendritic cells. J Neuroimmunology.333:476953. *corresponding author
2. Kaushansky N., E. Bakos, S. Becker-Herman, I. Shachar*, and A. Ben-Nun* . 2019. Circulating
picomolar levels of CCL2 downregulate ongoing chronic EAE by induction of regulatory
mechanisms. J Immunol. 203(7):1857-1866 *Co- last author.
3. Zilkha-Falb, R., Kaushansky N., and A. Ben-Nun"The Median Eminence, a new oligodendrogenic niche
in the adult mouse brain”, Stem Cells report, under minor revision.
Prof. Ben Nun’s research focused on autoimmune diseases, in particular on Multiple Sclerosis (MS). Multiple sclerosis (MS) is a disease of the human central nervous system (CNS), characterized by perivascular inflammation accompanied by primary demyelination and axonal damage. Although the etiology of the disease is unknown, it is believed that MS results from autoimmune mechanisms, leading to the destruction of myelin, presumably initiated by abnormally activated, potentially pathogenic, autoimmune T cells that recognize components of the myelin sheath in the CNS of MS patients. One of Avi’s major contributions, which was considered a breakthrough in the field of immunology, was the in vitro production of T cells against myelin epitopes. Following injection of these cells, mice develop MS-like disease (experimental autoimmune encephalomyelitis, EAE). This find was published in the top-tier journal Nature and paved the way for the development of therapies for MS and several other diseases. Prof. Ben Nun’s research contributed to the identification of potential target antigens in MS, e.g. myelin oligodendrocyte glycoprotein (MOG), myelin-oligodendrocytic basic protein (MOBP), and oligodendrocye specific protein (OSP). Injection of these antigens to laboratory animals resulted in EAE and T-cell reactivity against these antigens in MS patients were detected. MS is a complex and dynamic anti-myelin autoimmune disease. Prof. Ben Nun therefore believed that the ultimate goal of immune therapy for MS is a multi-target approach to immune-specific modulation that targets only the deleterious autoimmune T cells without compromising the immune competence of normal physiological functions. He also examined the use of stem cells for the regeneration and repair of damaged myelin in MS. Prof. Ben-Nun's scientific contribution constitutes a milestone in the world of immunology and in the study of autoimmune diseases in particular
Prof. Michael Feldman (1926-2005)Professor Feldman graduated from the Hebrew University in Zoology and trained with noted embryologist and philosopher of science Conrad Hal Waddington at the Institute of Animal Genetics in Edinburgh. Michael joined the Weizmann Institute in 1955, was promoted to full professor in 1961, and at the same year founded the Department of Cell Biology, which he headed until his official retirement in 1990.
As a professor Emeritus he joined the department of immunology when departments were rearranged. In the intervening years he also served for varying periods of time as Dean of the Faculty of Biology and of the Feinberg Graduate School, Chairman of the Weizmann Institute Scientific Council, visiting professor at Stanford University and at the Memorial Sloan Kettering cancer Institute, New York, and also served as Fogarty Scholar in Residence at the NIH. In 1977 he was elected Member of the Israel Academy, and in the following years received a number of national and international awards, including the Rothschild Prize, Honorary Doctorate of Ben Gurion University of the Negev, Honorary Fellowship of the Open University of Israel, Membership of the World Academy of Arts and Sciences and the San Marino Prize for Medicine. His activities in scientific and other areas in Israel and worldwide are too many to mention.
Professor Feldman’s research interests were primarily immunology and cancer research with special focus on metastasis. He also contributed seminaly to other fields like macrophage biology and transplantation. He published over 350 papers and book chapters. Michael was one of the rare scientists who could traverse comfortably the fields of both science and art. His many friends and admirers included not only with scientists in Israel and elsewhere, but also writers, painters and politicians.
Prof. Ofer Lider (1955-2004)Ofer Lider began his PhD in 1983 in the Department of Immunology at the Weizmann Institute of Science, despite having recently been diagnosed with leukemia (CML). He completed his degree in the laboratory of Irun Cohen in 1987 and went on to a post-doctoral fellowship with Howard Weiner at the Harvard Medical School (1987-9). He returned to establish his own laboratory in the Department of Immunology, where he studied the regulation of the immune system and its interactions with the extra-cellular matrix (ECM). His unique research achievements earned him international acclaim and a professorship with tenure at the Weizmann Institute in 2001. Various treatments including two bone marrow transplantations failed to cure his leukemia, and Ofer Lider died in 2004 at the age of 49.
Despite his illness, Ofer went on to form a perfect union with Osnat, raise three daughters, create a family and build a home. He was a leader who never commanded, never asserted his will, never imposed. His influence rested on his quiet nobility and his care for the feelings of others. Ofer always made time to listen, to comfort, to advise, to identify with the fear and the pain of others. For himself, he always knew what was truly important, and he used his time well. Towards the end of his life, he wrote and published poetry, including the highly regarded book Beynotayim (In the Meantime). Despite his short years, Ofer lived many times over the measure of life lived by others. His life was his poetry.
In the spirit of his memory, Ofer’s family, friends and colleagues established a non-profit association dedicated to fostering the literary expressions of scientists in poetry and short stories – Life’s Verse (Shirat Hayav). This enterprise is now sponsored by the Weizmann Institute of Science as The Poetry of Science (Shirat HaMada). For more than a decade, over a thousand literary works have been submitted to the annual competition. In this enterprise, Ofer’s courageous life of creative science and literary creativity continue to enrich science and art.
Prof. Israel Schechter (1935-2012)Israel Schechter first studied the active site of enzymes (proteases) discovering that their size is larger that expected, with important interactions in regions remote from the catalytic site allowing high binding energy of enzyme-inhibitor complexes. This led to rational design of inhibitors developed at 1990th into drugs against HIV (inhibitors of virus proteases) and revolutionized AIDs disease turning a lethal into a chronic disease. Other drugs were against hypertension, congestive heart failure, diabetes, cancer (methotrexate), bacteria (antibiotics), anti-viral (relenza) but also Viagra.
The Schechter-Berger model of the active site of enzymes divided into subsites (1967) became a milestone in enzymology and a template for drug design. His studies on the antibody combining site (1967) revealed a region of four subsites of independent Interactions being just additive, i.e., ligand’s binding energy was the sum of binding energy attained in each subsite. Israel also studied the biological aspects of the immune response focusing on cellular localization of antigen in relation to antibody producing cells. Other studies focused on immunological tolerance, antigenic competition, the role of antigen conformation on immunogenicity as well as the development of skin grafts with decreased immunogenicity and increased resistance to infection for the treatment of burnt patients. He also studied the molecular biology of schistosome, the cause of bilharzia., in collaboration with Egyptian scientists. Back in 1973 a major attention was devoted to the evolution of antibody diversity with the primary goal of isolating an immunoglobulin (Ig) gene. He was the first one to isolate pure mRNA encoding for a single protein (which could be translated to the first gene). He developed a general procedure based on the specific immune precipitation of polysomes engaged in the synthesis of a given molecule – here the Ig. The mRNA which was translated into the Ig precursor containing a signal peptide of marked hydrophobicity while intracellular but cleaved upon secretion, later identified as a property of other proteins as well.
Prof. Nathan Trainin (1922-1999)Born in Argentina Nathan graduated Medical school of the University of Cordoba and made Aliya to Israel in 1949 with his wife Zila. They settled in Kibuz Maabarot where he served as a rural physician, riding on horse, visiting settlements of new immigrants. He then served in the IDF as a physician. After release from service in 1956, he joined the Department of Experimental Biology of the Weizmann Institute, headed by Prof. Isaac Berenblum.
He focused on cancer research, studying a possible two stage mechanism in experimental leukomogenesis, using radiation and chemicals such as Urethan. He then moved to study the function of thymic tissue in diffusion chambers implanted in neonatally thymectomized mice. This led him to discover a thymic humoral factor shown to prevent wasting and influencing lymphopoiesis in such mice. He then proceeded to characterize this factor focusing on its role in the development of cell-mediated immune competence. In collaboration with Prof. Yigal Burstein from the Department of Organic Chemistry, the Thymic Humoral Factor (THF) has been purified from calf thymus and sequenced as an octapeptide. Together with Prof. Rina Zaizov from the Dept. of Pediatric Oncology at the Beilinson hospital a beneficial effect of THF in immunosuppressed children with lymphoproliferative neoplasia and generalized varicella was observed. Furthermore, in collaboration with Prof. Shlomo Ben-Efraim from the Tel Aviv University medical school, it was discovered that THF repairs immunodeficiency of mice cured from plasmacytoma. With Dr. Marit Pecht it was found that THF potentiates myeloid colony formation in bone marrow of intact and neonatally thymectomized mice. He published more than 200 papers and reviews. This research has been interrupted by the untimely death of Nathan.
Besides his research conducted almost till his last days, Nathan contributed to the society, heading the Israel CancerAssociation and helping cancer patients with advice and empathy.