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NIDDK Glycobiology Expert Ginsburg Dies

By Joan Chamberlain

Dr. Victor Ginsburg, an NIDDK scientist who pioneered the field of glycobiology, died Mar. 12 at Suburban Hospital.

Ginsburg retired in 1991 as chief of NIDDK's Laboratory of Structural Biology. He devoted most of his career to studying the complex carbohydrates that cover the surface of many cells and dictate their interactions with other cells as well as bacteria, viruses and biological toxins. His work helped to define how carbohydrate molecules govern cell communication and contribute to the development of diseases as diverse as cancer and infection at a time when few scientists appreciated the role these substances play in the recognition of other molecules.

"Vic Ginsburg was a prime mover in the development of glycobiology, making key contributions to structural, enzymological and biological aspects of this field. He was both a great scientist and a terrific person with a wonderful sense of humor," recalled NIDDK's Dr. Reed Wickner.

Dr. Victor Ginsburg

A 1964 paper co-authored by Ginsburg and B.M. Gesner in the Proceedings of the National Academy of Sciences "cracked open the door and lit up the field of glycobiology," said Dr. John Magnani, who worked as a biochemist in Ginsburg's lab. Ginsburg's team found that when they used enzymes called glycosidases to clip off sugars from rat lymphocytes, the fate of those cells dramatically changed. When the treated white cells were reinjected into the animals, they migrated to the liver instead of homing, as they normally did, to the spleen and lymph nodes.

To explain these results, Ginsburg postulated two receptor systems for carbohydrates. The enzymes had destroyed the outermost carbohydrates on the lymphocytes' surface, structures that normally bind to a receptor in lymphoid tissue. "This interaction could be a critical event that controls the selective migration of lymphocytes from the blood into lymphoid tissue," he speculated. In addition, the enzymes had exposed underlying carbohydrate structures on the surface of the lymphocytes, forcing the cells to bind to a receptor in the liver. Both hypotheses later proved correct, though it would take years to confirm them.

Dr. Gilbert Ashwell of the National Institute of Arthritis and Metabolic Diseases and colleagues identified the second receptor, now known as the asialoglycoprotein receptor in the liver. "The first receptor took many years to discover," said Magnani. "Eventually, it became clear that selectin receptors, as they are now called, play a crucial role in promoting inflammation and cancer metastasis."

With the publication of the PNAS paper, the study of carbohydrates as recognition molecules suddenly came into its own. As glycobiology researcher D.A. Rees put it in 1971, "the ugly ducklings have begun to look a little more like swans…carbohydrates are beginning to appear attractive…shapely molecules" instead of the drab, uninteresting structures they were once perceived to be. Scientists would eventually learn that carbohydrates are important in a variety of cell interactions, from the attachment of bacteria to tissues in the early stage of infection, to the promotion of metastasis in some types of cancer. Currently, researchers are exploiting this knowledge to develop drugs that prevent infection or metastasis by blocking or neutralizing the binding of carbohydrates to proteins or other carbohydrates.

In other work, Ginsburg and British researcher W.M. Watkins helped prove that people have specific, genetically determined sugars on the surface of their cells that specify their A, AB, B and O blood types. By isolating and studying the glyco-syltransferase enzymes responsible for the attachment of specific sugars to red blood cells, they showed, for example, that only people with blood types B or AB have the transferase for the sugar galactose, the determinant of those blood types.

"Vic will be well remembered for his seminal contributions to the fast growing field of glycobiology," said Dr. Nathan Sharon of Israel's Weizmann Institute of Science, who first met Ginsburg on a visit to NIH 40 years ago. In 1978, he and Ginsburg organized the first conference on glycobiology, "Complex Carbohydrates in Biological Recognition," sponsored by the Fogarty International Center. "I was captivated by Vic's kind, warm personality, his wit and delicate sense of humor, and his incisive mind," said Sharon. "We had a close friendship. Vic was proud of his collection of antique books, his paintings and book bindings."

"As a lab chief and mentor, Victor Ginsburg had a sharply critical mind and little patience for poor research. At the same time, he was jovial, good natured, and very loyal and supportive of the researchers he mentored," remembers John Magnani, who now heads Glycotech Corp. and is planning a symposium to honor Ginsburg's work. (For more information, email or call 301-738-1084.)

Born in Singapore on Mar. 22, 1930, Ginsburg moved to San Francisco at age 4 and obtained his Ph.D. in biochemistry from the University of California at Berkeley in 1955. He came to NIH in 1956 as a postdoctoral fellow in the PHS to work with Dr. Herman Kalckar. After pursuing a 1-year fellowship in Belgium with the Polio Foundation under the sponsorship of Prof. G. Hers, he returned to NIAMD in 1959, joining the Laboratory of Biochemistry and Metabolism under Dr. Gordon Tomkins. In 1965, he became chief of the section on biochemistry in Dr. Herbert Tabor's Laboratory of Biochemical Pharmacology. He was chief of NIDDK's structural biology lab from 1986 until he retired.

Ginsburg is survived by his wife, Dr. Ann Ginsburg, who heads NHLBI's section on protein chemistry; two children, Mark Ginsburg and Lisa Ginsburg; a sister, Helen Benjamin in Cambridge, UK, and her three children; and three grandchildren, Ava, Daniel and Lily who reside in Providence, RI.

NIGMS Council Member Herskowitz Dies

Dr. Ira Herskowitz, a member of the National Advisory General Medical Sciences Council and a long-time NIGMS grantee, died of pancreatic cancer on Apr. 28. He was 56 years old.

Dr. Ira Herskowitz

Herskowitz was co-director of the program in human genetics in the School of Medicine at the University of California, San Francisco, where he was also a professor in the department of biochemistry and biophysics. He studied the control of gene expression in yeast, cell signaling, cell morphogenesis and growth control and pharmacogenetics. On the day he died, the Proceedings of the National Academy of Sciences published two articles that Herskowitz co-authored as a member of the NIH pharmacogenetics research network.

Herskowitz earned a B.S. degree in biology from the California Institute of Technology and a Ph.D. in microbiology from the Massachusetts Institute of Technology, where he also conducted postdoctoral research.

He was a member of the National Academy of Sciences and a fellow of the American Academy of Arts and Sciences, the American Association for the Advancement of Science and the American Academy of Microbiology. Herskowitz's honors include a MacArthur Foundation fellowship from 1987 to 1992 and the Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research in 2003.

He is survived by his parents, a sister and two brothers.

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