Dr. George Palade, the UC San Diego Nobel laureate whose work isolating, imaging and identifying the function of minute organelles within cells prompted the Nobel committee to label him and his co-winners the fathers of cell biology, died Tuesday at his home in Del Mar, Calif., after a long illness. He was 95.
Working in the 1950s and '60s, Palade took advantage of the newly developed techniques of differential centrifugation to separate the intracellular components and electron microscopy to image them. Using those techniques, he identified the function of, among other things, mitochondria, the power plants of the cell, and ribosomes, the protein-making machinery.
"Dr. Palade had a tremendous impact on the course of science, as well as a personal impact on countless colleagues and students who were inspired by his teaching and example," said UCSD Chancellor Marye Anne Fox.
"George Palade was not only one of the leading scientists of his era, but was a pioneer in modern cell biology, using electron microscopy to study and describe subcellular structures for the first time," said Dr. David A. Brenner, vice chancellor for health sciences.
When Palade immigrated to the United States from Romania in 1946, most studies of cellular interiors had been performed with optical microscopes, which magnify objects only about 1,000-fold and thus cannot resolve the finer details of structure.
Electron microscopes, first produced commercially in 1939, could easily exceed the 10,000X magnification required to see the interior of the cell and can now give magnifications of 2 million or more.
But time was required to develop techniques to isolate appropriate specimens and prepare them for the microscope.
Working with Albert Claude at the Rockefeller Institute for Medical Research -- now Rockefeller University -- in New York, Palade began developing ways to separate cellular components. He, George Hogeboom and Walter Schneider developed the widely used sucrose gradient technique in which cells are first homogenized in a blender to break up cellular membranes.
The homogenate was then layered onto the surface of a test tube containing sugar water, with a very high concentration of sucrose at the bottom and steadily decreasing concentrations at higher levels. When the test tube was spun at high speeds in an ultracentrifuge, the heaviest cellular components, such as the nucleus, would sink into the densest layer at the bottom, while lighter components would segregate at different levels, allowing Palade to isolate individual components of the cell.
He then turned to electron microscopy, developing techniques to produce thin slices of cells and to "fix" these slices and the substances isolated by centrifugation -- attaching them to a substrate for viewing.
His first target was mitochondria, tiny organelles scattered throughout the cell. He detailed their fine structure, demonstrating that they oxidize fats and sugars, producing chemical energy in the form of adenosine triphosphate, or ATP, that can be used by the rest of the cell.
He then discovered even smaller organelles, called microsomes, which were initially thought to be part of the mitochondria. He demonstrated that they functioned independently and were rich in ribonucleic acid, or RNA. They proved to be the site where proteins were assembled in cells and were ultimately renamed ribosomes.
Palade also discovered and studied the endoplasmic reticulum, a system of folded membranes that permeates the cytoplasm of cells and provides a large surface area for chemical reactions. Studying more than 40 different types of cells from birds and mammals, he demonstrated that the endoplasmic reticulum is a vital component of all types of body cells except the mature red blood cell.
Looking at the larger picture, then, in a series of papers that the Nobel committee described as "extremely elegant," Palade and Keith Porter traced the path of secretory cells -- such an insulin-producing cells in the pancreas -- through the cell.
The protein product is first produced in ribosomes on the outside of the endoplasmic reticulum.
It then migrates to the space inside the reticulum's membrane, accumulating in the Golgi complex, where it is altered into a form suitable for secretion.
"Many fascinating details of the secretory process were demonstrated," the Nobel committee said.
It was for this whole series of experiments that Palade shared the 1974 Nobel Prize in Physiology or Medicine with Albert Claude and Christian de Duve.
George Emil Palade was born Nov. 19, 1912, in Jassy, the old capital of Moldavia, the eastern province of Romania. His father was a professor of philosophy who hoped his son would follow in his footsteps.
But, "influenced by relatives who were much closer to my age than he was," Palade enrolled in the School of Medicine at the University of Bucharest, training in internal medicine and receiving his medical degree in 1940.
He spent the war years in the medical corps of the Romanian army, but it became clear to him that his interests lay more in anatomy and function rather than patient care.
In 1973, he left Rockefeller for Yale University, where he was chairman of the new department of cell biology. Seventeen years later, he went to San Diego, where he became the founding dean for scientific affairs. He retired in 2001 but remained a consultant.
Among his many other honors were the National Medal of Science, the Albert Lasker Award for Basic Medical Research and the Louisa Gross Horwitz Prize.
His first wife, Irina Malaxa, died in 1969. In 1970, he married Marilyn Gist Farquher, a cell biologist.
In addition to his wife, he is survived by a daughter, Georgia van Deusen of New York; three sons, Bruce and Douglas, both of San Diego, and Philip of Little Rock, Ark.; and two grandchildren.
Memorial services are pending.