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Vol.26, No. 08 Oct. 30, 2000

Horwitz Prize Goes To MITís Horvitz, Harvardís Korsmeyer

Columbia’s Louisa Gross Horwitz Prize honored the joint accomplishments of two researchers, H. Robert Horvitz and Stanley J. Korsmeyer, who collectively described several cellular mechanisms controlling programmed cell death, or apoptosis, a process crucial to normal development as well as immune function, at a dinner in Low Rotunda on Nov. 8.

Horvitz is Whitehead Professor of Biology at the Massachusetts Institute of Technology, and Korsmeyer is Sidney Farber Professor of Pathology and Professor of Medicine at the Dana-Farber Cancer Institute at Harvard Medical School. The work of Horvitz and Korsmeyer, both Howard Hughes Medical Institute Investigators, demonstrated the universal importance of several cellular mechanisms in regulating apoptosis in both vertebrates and invertebrates.

The prize is given annually to recognize exceptional accomplishments in biological and biochemical research, considered by many to be the precursor of the Nobel prize. In choosing the recipients for the Horwitz Prize, the selection committee designated by Columbia President George Rupp favors recent research not previously recognized by a major award, but which may represent the cumulative work of more than one researcher over decades.

Probably as important in development and disease as cell division and the specification of cell types, apoptosis is essential in eliminating superfluous or damaged cells. This “cell suicide” response can be triggered by normal developmental signals, disease-related deterioration or cell damage resulting from toxic exposure, low oxygen or traumatic injury. Once the pathway is unleashed, the cell’s DNA is minced into fragments and the cell awaits engulfment and removal by macrophages, the immune system’s “clean-up” crew.

Aside from the role of apoptosis in embryonic development, misregulation of apoptosis may contribute to cancer and autoimmune and neurodegenerative diseases. Teasing apart the components of the cell’s system for regulating apoptosis may greatly further understanding of diseases as well as the ability to treat them.

Apoptosis is orchestrated and tightly regulated by interconnected intracellular pathways involving proteins that act as death activators or as inhibitors. Several of these important proteins were identified by Horvitz and Korsmeyer. As discoverers of crucial parts of the cell death machinery and the genes that encode them, the two researchers have contributed substantially to the understanding of apoptosis.

Korsmeyer is recognized for his discovery in 1985 of bcl-2, a gene whose activity was changed in human follicular B-cell lymphoma. In 1989, Korsmeyer showed that overexpression of the bcl-2 gene in transgenic mice led to an increase in the number of B cells by enhancing their survival. This demonstration that a defect in regulation of cell death could play a role in tumor growth prompted extensive expansion in research on apoptosis.

Horvitz is credited with identifying many of the components of the biochemical cascade mediating apoptosis in the worm, Caenorhabditis elegans. In 1986, Horwitz discovered two genes that were required for cell death. In 1993, he showed that one of these genes, ced-3, encodes an enzyme called a caspase. Several caspases are now known to be crucial components of the biochemical cascade that culminates in cell death.

CED-3, the protein product of the ced-3 gene, is activated by CED-4, which is the protein product of the second gene identified by Horvitz. In addition, he discovered the gene encoding CED-9, a regulatory protein that sequesters the CED-4 protein, thereby preventing CED-3 activation and stalling the chain of biochemical events that lead to cell death. Later, Horvitz showed that CED-9 was similar to the product of the bcl-2 gene discovered by Korsmeyer, demonstrating the generality of mechanisms involved in apoptosis in both vertebrates and invertebrates alike.

Columbia has awarded the annual Horwitz Prize since 1967. The prize is named after Louisa Gross Horwitz, the mother of the late S. Gross Horwitz, who sponsored the award with a gift to the University. Louisa Gross Horwitz was the daughter of Samuel David Gross of Philadelphia, who authored a classic surgical text and served as a president of the American Medical Association during the 19th century.

—Office of External Relations, Columbia University Health Sciences Division, hsdnews@columbia.edu