From Intracellular Morphology to Function: The Secretory Pathway

The field of modern cell biology was forged from advances in both electron microscopy and biochemical analysis of cell fractions. At the center of this emerging discipline was George Palade (1912-2008). Not only did he pioneer analytical techniques and discover new cellular structures, he also used biochemistry to unite structure with function. In the 1950s and 1960s, having discovered ribosomes and their association with the endoplasmic reticulum, he detailed the pathway by which proteins are made in, transported through, and discharged from secretory cells. For this achievement, in 1974 he was awarded the Nobel Prize, shared with Albert Claude (1899-1983) and Christian de Duve (1917- ).

Palade, George

Palade arrived at Rockefeller in 1947, shortly after Albert Claude and Keith Porter (1912-1997) published the first electron micrograph of an intact cell. With colleagues in Claude's research group in the laboratory of James B. Murphy, Palade worked to improve the techniques for imaging cells. He developed the sucrose method for cell fractionation, by which organelles could be isolated without distorting their shapes, and he used osmium tetroxide to obtain better contrast with electron microscopy. With these methods, Palade became the first to isolate intact mitochondria and describe the fine structure of this organelle. He spent several years continuing to map the structures inside the eukaryotic cell, focusing in particular on the endoplasmic reticulum and chemical synapses, while developing improved methods of preparing and fixing samples in thin slices.

In order to learn how cellular structures carry out their functions, Palade returned to fractionation techniques in the 1950s, but now also employed other techniques, including biochemical analysis and autoradiography; he later developed the method of pulse-chase labeling in tissue slices. In 1955, he made his landmark discovery of the ribosome (originally called the Palade granule), the protein making factory within the cell. With Philip Siekevitz, he published a series of classic papers tracing the pathway of secretory proteins from synthesis to release from the cell. With Marilyn Farquhar, he described complexes that connect epithelial cells.

In elucidating how cells are organized and regulated, Palade helped lay the groundwork for a new approach to medicine. In his words, "Cell Biology finally makes possible a century old dream: that of analysis of diseases, at the cellular level—the first step towards their final control." Furthermore, in addition to his many scientific contributions at the core of modern cell biology, Palade was an important figure in organizing the new discipline. Rockefeller became famous for electron microscopy in the 1950s, and researchers from around the world came to train in Palade's laboratory. When the new group of cell biologists found that existing journals could not print high-quality reproductions of electron microscope images, and often rejected their interdisciplinary papers, Palade and others started the Journal of Biophysical and Biochemical Cytology, which began publication at the Rockefeller Institute in 1955. In 1962 the name was changed to the Journal of Cell Biology. Palade also was a founding member of the American Society for Cell Biology, established in 1960.

Diagram of intracellular transport. From Science, 1975, 189: 347-358

George E. Palade received the MD from the University of Bucharest, Romania (1940). He joined the faculty of the anatomy department at the university, and during World War II served in the medical corps of the Romanian army. In 1946 Palade came to the United States for postdoctoral research at New York University. Albert Claude, who was working under James B. Murphy, invited Palade to come to Rockefeller the following year. The two had met after a seminar Claude gave describing his work in electron microscopy. In 1951 Palade moved to the laboratory of Herbert Gasser, then director of the Rockefeller Institute. He became professor, with his own laboratory, in 1956. Palade remained at Rockefeller until 1973, when he moved to Yale University to become professor and chair of the section of cell biology. In 1990 he moved to the University of California at San Diego, where he was the first dean of scientific affairs. In addition to the Nobel Prize (1974), Palade's research was recognized with the Lasker Award (1966), the Gairdner Special Award (1967), the Louisa Gross Horwitz Prize (1970, shared with Albert Claude and Keith Porter), and the National Medal of Science (1986). He was an elected member of the U.S. National Academy of Sciences (1961) and served as president of the American Society for Cell Biology in 1974-1975. A postage stamp in Palade's honor was issued by Romania, his native country, in 2001.

Selected Publications

Hogeboom GH, Schneider WC, and Pallade GE. Cytochemical studies of mammalian tissues. I. Isolation of intact mitochondria from rat liver; some biochemical properties of mitochondria and submicroscopic particulate material. J Biol Chem, 1948, 172: 619-635

Palade G.E., et al. A small particulate component of the cytoplasm. J Biophys Biochem Cytol,  1955, 1: 59-68

Siekevitz P and Palade GE. A cytochemical study on the pancreas of the guinea pig. I. Isolation and enzymatic activities of cell fractions. J Biophys Biochem Cytol, 1958, 4: 203-218

Siekevitz P and Palade GE. A cytochemical study on the pancreas of the guinea pig. II. Functional variations in the enzymatic activity of microsomes. J Biophys Biochem Cytol, 1958, 4: 309-318

Siekevitz P and Palade GE. A cyto-chemical study on the pancreas of the guinea pig. III. In vivo incorporation of leucine-1-C14 into the proteins of cell fractions. J Biophys Biochem Cytol, 1958, 4: 557-566

Siekevitz P and Palade GE. A cytochemical study on the pancreas of the guinea pig. IV. Chemical and metabolic investigation of the ribonucleoprotein particles. J Biophys Biochem Cytol, 1959, 5: 1-10

Siekevitz P and Palade GE. A cytochemical study on the pancreas of the guinea pig. V. In vivo incorporation of leucine-1-C14 into the chymotrypsinogen of various cell fractions. J Biophys Biochem Cytol, 1960, 7: 619-630

Siekevitz P and Palade GE. A cytochemical study on the pancreas of the guinea pig. VI. Release of enzymes and ribonucleic acid from ribonucleoprotein particles. J Biophys Biochem Cytol, 1960, 7: 631-644

Siekevitz P and Palade GE. Cytochemical study on the pancreas of the guinea pig. VII. Effects of spermine on ribosomes. J Cell Biol, 1962, 13: 217-232

Farquhar MG and Palade GE. Junctional complexes in various epithelia. J Cell Biol, 1963, 17: 375-412

Palade G. Intracellular aspects of the process of protein synthesis. Science, 1975, 189: 347-358

Further Reading

Kresge N, Simoni RD, and Hill RL. George Emil Palade: How sucrose and electron microscopy led to the birth of cell biology. J Biol Chem, 2005, 280: 19

Blobel G. Obituary: George Emil Palade (1912-2008). Nature, 2008, 456: 52

Jamieson JD. A tribute to George E. Palade. J Clin Invest, 2008, 118: 3517-3518

Rasmussen N. Picture control: The electron microscope and the transformation of biology in America, 1940-1960. Stanford Univ Press, 1999

Bechtel W. Discovering cell mechanisms: The creation of modern cell biology. Cambridge Univ Press, 2006


The Nobel Prize in Physiology or Medicine, 1974

Albert Lasker Basic Medical Research Award, 1966