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In memoriam: William T. Norton (1929–2018)

2019; Wiley; Volume: 150; Issue: 6 Linguagem: Inglês

10.1111/jnc.14798

1471-4159

Robert K. Yu,

Various Chemistry Research Topics

This is an obituary for William T. Norton (1929-2018) who died in Palo Alto, California on December 17, 2018, about one month short of his 90th birthday. Very few people in the contemporary neurochemical field have exerted more influence than Bill Norton in shaping the directions of research in this field. Before retiring from an active career after 40 years of service at the Albert Einstein College of Medicine, Bronx, NY, Bill made remarkable contributions in neurochemistry, as a researcher, a teacher, and a statesman. Many of his discoveries have become classics. His clear thinking, critical judgment, and passion for excellence in science helped to build the field of neurochemistry as a distinct discipline in neuroscience. William T. (Bill) Norton was born on January 27, 1929 in Damariscotta, Maine, and died peacefully in Palo Alto, California on December 17, 2018, about one month short of his 90th birthday. He was predeceased by his long-time wife, Lila (nee, Mazur). A memorial service, arranged by his two sons, Hamish and Adam, was attended by many of his professional friends, students, relatives, and admirers on February 2, 2019 in New York City. Very few people in the contemporary neurochemical field have exerted more influence than Bill Norton in shaping the directions of research in this field. Before retiring from an active career after 40 years of service at the Albert Einstein College of Medicine, Bronx, NY, Bill made remarkable contributions in neurochemistry, as a researcher, a teacher, and a statesman. Many of his discoveries have become classics. His clear thinking, critical judgment, and passion for excellence in science helped to build the field of neurochemistry as a disctinct discipline in neuroscience. Bill received his AB degree in chemistry from Bowdoin College, Maine, in 1950, and then received his MS and PhD degrees in organic chemistry in 1952 and 1954, respectively, from Princeton University. His doctoral dissertation was on the mechanisms of the Diels-Alder reaction, an important reaction in synthetic chemistry. This early training with a strong chemistry background brought him to DuPont Chemical Company, Wilmington, Delaware, as a Research Chemist. Shortly thereafter, he was recruited to the Department of Neurology of the newly formed Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, in 1957 as a Senior Postdoctoral Fellow and Instructor. This move proved to be epithetic in defining his stature as a pioneering neurochemist. The Founding Chair of the Department of Neurology at Einstein was Dr Saul Korey, who had the unusual vision of developing a clinical department with a strong basic sciences program. He recruited Bill, Bob Ledeen, Kunihiko Suzuki, and several others to form a particularly talented core of basic sciences research in a clinical department, a bold but far-sighted move at that time. The arrival of Kuni Suzuki was particularly fortuitous because of his clinical training and basic science expertise. After Dr Korey died prematurely, the new Chair, Dr Robert Katzman, continued to build the Department on the same path. Shortly thereafter, Pierre Morell joined the Department. Together they formed a core of basic neurochemical research. At the same time, the laboratories of Maurice Rapport, Barry Bloom, Cedric Raine, Henryk Wisnewski, Kinuko Suzuki, Bob Terry, Dom Purpura and many others were all close by, making Einstein one of the most formidable centers for research and education in neuroscience. Cutting-edge research was done and new discoveries were reported almost monthly. Bill, with his clear thinking and brilliant mind, was always in the midst of those exciting discoveries. His own research efforts, notably in myelin and glia biology research, were well recognized and helped in influencing the direction of early neurochemical research. During that time, research in neuroscience in general and neurochemistry in particular began to flourish. This resulted in the establishment of the American Society of Neurochemistry, which held its first meeting in 1970 in Albuquerque; this was a year before the Society for Neuroscience held its first meeting in Washington, DC. In a relatively shortly period of time, Bill rose through the ranks, being promoted to Full Professor of Neurology (Neurochemistry) in 1971, and Professor of Neuroscience in 1974. He held that position until his retirement in 1998 as Professor Emeritus of the Saul Korey Department of Neurology and Professor Emeritus of the Dominic Purpura Department of Neuroscience. Trained as an organic chemist, Bill's work was always greatly influenced by his keen knowledge in chemistry. He first elucidated the structures of plasmalogens, which belong to a class of phospholipids containing a vinyl ether linkage at the sn-1 position of the glycerol backbone. Thus, they are structurally and chemically different from the usual phospholipids, which possess two acyl linkages at the sn-1 and −2 positions. Because of this unusual structure, plasmalogens are sensitive to mild acid. Taking advantage of this difference, Bill's initial efforts were to establish a novel method for the quantitative measurement of plasmalogens that are present in high concentrations in myelin (Norton, 1960). He then developed a specific histological stain for these compounds using diphenylcarbazone to detect bound mercury (Norton, 1959). This early work led to further studies on the chemistry and biology of the myelin membrane, and he rapidly became one of the foremost world authorities on the isolation and composition of this component of brain membrane, a unique lipid-rich membrane that is still the focus of major attempts to determine the cause of many neurological disorders, such as Multiple Sclerosis. Bill's first studies of myelin, published in 1964 with Lucy Autilio, addressed the problem of making a pure preparation from bovine brain, free of microsomal contaminants so that an accurate analysis of myelin composition could be obtained (Autilio et al., 1964; Norton and Autilio 1966). It may be characteristic of Bill's personality that, having developed in 1967 a method for preparing pure myelin that could be applied to rat brain at any stage of development, he generously made this method available to other investigators. The details of a final method were published, with Shirley Poduslo, in 1973 (Norton and Poduslo 1973a,1973b). In the meantime, at least half a dozen other investigations were able to proceed using this necessary information. The initial basic research on myelin and glia was followed by studies on a proposed mechanism underlying demyelinating diseases, namely those characterized by an inflammatory process in which axons are generally spared. The hypothesis was that demyelination might be the result of the action on myelin basic protein, a protein highly susceptible to proteolysis, of neutral proteinases secreted by macrophages. This concept was pursued with his collaborators, Barry Bloom, Wendy Cammer, Celia Brosnan, Ellen Goldmuntz, and others, for a number of years, and led to the demonstration that protease inhibitors could suppress experimental allergic encephalopathy (EAE), an animal model of multiple sclerosis. However, they eventually concluded, as knowledge of the complexity of the inflammatory process continued to develop, that proteolysis is only one factor contributing to demyelination (Cammer et al. 1978). Another major focus in Bill's laboratory carried out by George DeVries, a postdoctoral fellow, in the early 1970s was the fractionation of brain white matter to obtain axons and neurofilaments. Gentle homogenization of white matter in a buffered sucrose solution allowed myelin to stay intact around axons. Subsequent centrifugation allowed the myelinated axons to separate from other cellular elements by flotation to the surface. In this manner, axons and neurofilaments were isolated from myelinated axons of mammalian brain in quantities sufficient for biochemical characterization. (DeVries et al. 1972; DeVries and Norton, 1974; Norton et al. 1975). This led to a long series of studies with Alex Chiu, Jim Goldman, Ellen Goldmuntz, and others on the characteristics of intermediate filaments, culminating in the demonstration that astroglial filaments are composed of glial fibrillary acidic protein and are clearly distinguishable from neurofilaments. Using the floating axon method to obtain neurofilaments, further studies with Alex Chiu demonstrated from peptide mapping of the 70, 160, and 210 kDa subunit structures of neurofilaments that these proteins originated from separate mRNAs (Chiu et al. 1980; Chiu and Norton 1982). In those early days, cell culture techniques were still in their infancy and not reliable enough to provide pure preparations of cells and cell components for studying their chemical composition. Bill's major contributions beginning in the 1970s, in collaboration with Shirley Poduslo (Norton and Poduslo 1970; Norton and Poduslo 1971b; Poduslo and Norton 1975) and Muhammad Farooq (Farooq et al. 1977), were to isolate, from rat brain, neuronal perikarya, oligodendroglia, and astroglia in sufficient quantities by new techniques that yielded cell preparations considerably purer than those reported previously. The availability of relatively pure and well-defined cell and membrane preparations enabled Bill and others in the field to define their chemical compositions and to study their properties (Norton and Autilio 1966; Norton and Poduslo 1971a; Poduslo and Norton, 1972; DeVries et al. 1972; Goldman et al. 1978; Morell and Norton 1980; Farooq et al. 1981; Chiu et al. 1981; Norton et al. 1983; Norton et al. 1988; Yu et al. 1989). These monumental studies provided invaluable information to deduce aspects of the mechanisms of myelination, gliogenesis, and neurogenesis, that we begin to unravel today, employing newer and more powerful molecular and cellular technologies and tools unavailable at his time. It may be fair to say that throughout his career, Bill always demonstrated an acute understanding of the problem, a mastery of technology and experimental design, and a high level of intelligence and insight. These traits were evident from his science. His monumental contributions to neuroscience have indeed greatly enriched the neurochemical community throughout the world. Bill's love of science was legendary and inspired many of his academic offspring who surrounded him at Einstein. He set a high mark for them to achieve. He was genuinely interested in education: training clinicians, medical students, and postdoctoral fellows in his laboratories. He had a way of bringing out the best in each of the trainees who came his way. He always looked to instruct his students beyond mere science and was genuinely concerned that the whole person be educated. An anecdote might serve as an example. He had a young scientist coming to his laboratory proposing to isolate myelin from earthworms. It quickly became apparent after his arrival that he did not have the necessary skills to perform laboratory research. Bill had to let him go and advised him to pursue clinical work instead. It turned out to be the best advice for this young scientist, who later became a world-renowned clinician and science writer. Many of Bill's academic offspring are leaders in the scientific community, a testament to his instruction in, and enthusiasm for, education and research. Bill had a remarkable ability to think simply and clearly about science and described its essentials that students and scholars could understand. In fact, he frequently instructed his students and mentees that: 'If you can't write clearly, you can't think clearly', which became his motto. This is particularly evident in all his scientific contributions. It is always a pleasure to read his publications for their clarity, thoroughness, and thoughtfulness. Over the years, Bill donated generously and unselfishly of his time and effort to the scientific community by serving as a member on the editorial boards of many journals, notably, as Associate Editor of the Journal of Lipid Research (1969–1972), Advisory Editor, Editor and Editor-in-Chief of the Journal of Neurochemistry (1972–1985), Brain Research (1973), Developmental Brain Research (1981), Developmental Neuroscience (1978–8192), and International Journal of Developmental Neuroscience (1983–1992). He was elected as President of the American Society for Neurochemistry (1987–1989) and was Chair of the Publications Committee (1989–1995) of the International Society for Neurochemistry. He also won many coveted awards, among them the Lena and Joseph Gluck Distinguished Scholar in Neurology (1969–1971) and the Jacob Javits Neuroscience Investigator Award, NIH (1984–1995). He also served on many advisory and review panels for NIH and other funding agencies and foundations. Bill had a wonderful family. His wife, Lila, whom he married in 1957, was a warm and caring lady who quietly and whole-heartedly supported his pursuit of science. They had two sons, Hamish (married to Deidre) and Adam (married to Mary Ann), and four grandchildren. Among many of Bill's hobbies, his love for motorcycling was probably the most legendary. He frequently went on long sightseeing trips on his motorcycle. Following his retirement, he remained eager for news of science and continued to go to his office to read and to advise young students. He visited his sons and their families often and made many trips to Maine. He also enjoyed a glass of single-malt whisky, especially in the presence of visitors. He remained mentally sharp and knowledgeable for most of his life. As one of Bill's admirers and followers, I frequently sought advice from him, not only for scientific reasons, but also for things of a personal nature. Bill was always very generous in sharing with me his wisdom, as he had done with others. It is with great admiration and affection that we say good-bye to Bill. The author is greatly indebted to Dr Hamish Norton and Mr. Adam Norton for much personal information about their father and their families. He also thanks Drs. Robert Ledeen and George DeVries for their invaluable suggestions and comments. The author has no conflict of interest.