April 2010

Philip Siekevitz (1918—2009)


Photo courtesy of Rockefeller University.

Philip Siekevitz, a pioneer in cell biology and a professor emeritus at The Rockefeller University, passed away Dec. 5 at age 91.

Siekevitz was born in Philadelphia (1918) and attended the Philadelphia College of Pharmacy and Science. He became interested in biochemistry and wanted to go to graduate school, but he was drafted into the Army in his final year of college. He managed to defer for a year and graduated in 1942.

After almost four years of service, Siekevitz enrolled at the University of California, Berkeley. Working with David Greenberg, he studied amino acid metabolism and became one of the first to use radioactive amino acids to look at in vitro protein synthesis using cells and tissue slices.

Siekevitz earned his doctorate in biochemistry in 1949. He then joined Paul Zamecnik’s laboratory at Harvard’s Massachusetts General Hospital, where he collaborated with Fritz Lipmann, studying mitochondrial biochemistry. While at Harvard, Siekevitz was among the first to use subcellular fractions, microsomes, mitochondria and nuclei to look at protein synthesis. Previously, this was done with whole homogenates or tissue slices. His work at Mass General played an early role in Zamecnik’s successful development of a system for cell-free protein synthesis.

In 1951, Siekevitz became a postdoctoral fellow in Van R. Potter’s laboratory at the University of Wisconsin, Madison, where he studied the regulation of energy metabolism in mitochondria.

Three years later, George Palade invited Siekevitz to work with him at Rockefeller University. He and Palade spent the next 20 years as colleagues. The pair first studied the pancreas as a system for protein synthesis and secretion and, using radioactive amino acids, showed that the secretory enzymes of the pancreas were first synthesized on ribosomes and then transported across the endoplasmic reticulum membrane into the organelle’s lumen, finally appearing in the zymogen granules that were secreted into the lumen of the intestine.

Next, Siekevitz and Palade became interested in membrane formation and found that various microsomal enzymes had different time courses of appearance in the endoplasmic reticulum. They demonstrated that there is a turnover of enzymes in the endoplasmic reticulum, with each protein having a characteristic half-life. From this, they inferred the presence of a substructure where newly synthesized enzymes were deposited.

Also, with Rachele Maggio, they carried out the first systematic fractionation of nuclei, leading to a clean separation of nucleoli and nucleoplasm that enabled a new era of biochemical investigation of the nucleus.

As an independent member of the Rockefeller faculty, Siekevitz changed the focus of his research to the nervous system and the events that occur at the neural synapse. By chance, he discovered postsynaptic density, a finding made a year earlier by Carl Cotman, and became convinced that the density represented a separate subcellular structure that underlies the postsynaptic membrane. For the next 16 years, Siekevitz and his colleagues incisively studied postsynaptic density, determining which proteins were attached to it. He retired from Rockefeller in 1988.

Siekevitz was elected to the National Academy of Sciences in 1975 and became the president of the American Society for Cell Biology in 1966 and president of the New York Academy of Sciences in 1976. He was an advocate of the social responsibilities of scientists and a founding member of the New York Scientists Committee for Public Information. He was also co-author of one of the first textbooks on cell biology, Cell Structure and Function, published in 1963.

Nicole Kresge (nkresge@asbmb.org) is the editor of ASBMB Today.


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