The Nobel Prize in Physiology or Medicine 1974
Albert Claude, Christian de Duve, George E. Palade
I was born in
November 1912 in Jassy (Iasi), the old capital of Moldavia, the
eastern province of Romania. My education was started in that
city and was continued through a baccalaureate (continental
style) at the "Al Hasdeu" Lyceum in Buzau. My father, Emil
Palade, was professor of philosophy and my mother, Constanta
Cantemir-Palade, was a teacher. The family environment explains
why I acquired early in life great respect for books, scholars
My father had hoped I was going to study philosophy at the University, like himself, but I preferred to deal with tangibles and specifics, and - influenced by relatives much closer to my age than he was - I entered the School of Medicine of the University of Bucharest (Romania) in 1930.
Early in my student years I developed a strong interest in basic biomedical sciences by listening to, and speaking with, Francisc Rainer and André Boivin, professors of Anatomy and Biochemistry, respectively. As a result, I started working in the Anatomy laboratory while still in medical school. I went, nonetheless, through six years of hospital training, mostly in internal medicine, but I did the work for my doctorate thesis in microscopic anatomy on a rather unusual topic (for an M.D.): the nephron of the cetacean Delphinus delphi. It was an attempt to understand its structure in terms of the functional adaptation of a mammal to marine life.
I graduated in 1940 and, after a short period as an assistant in internal medicine, I went back to Anatomy, since the discrepancy between knowledge possessed by, and expected from, the medical practitioners of that time made me rather uneasy.
During the second world war, I served in the medical corps of the Romanian Army, and after the war - encouraged by Grigore Popa, Rainer's successor - I came to the United States in 1946 for further studies. I worked for a few months in the Biology Laboratory of Robert Chambers at New York University and, while there, I met Albert Claude who had come to give a seminar on his work in electron microscopy. I was fascinated by the perspectives opened by his findings and extremely happy when, after a short discussion following his seminar, he asked me to come to work with him at The Rockefeller Institute for Medical Research in the fall of the same year. This was truly a timely development, since Chambers was retiring that summer.
At The Rockefeller Institute, Claude was working in the department of Pathology of James Murphy with George Hogeboom and Walter Schneider as direct collaborators; Keith Porter was in the same department but had developed his own line of research on the electron microscopy of cultured animal cells. At the beginning, I worked primarily on cell fractionation procedures, and I developed with Hogeboom and Schneider the "sucrose method" for the homogenization and fractionation of liver tissue. This first "Rockefeller group" had a rather short existence: Schneider returned to the University of Wisconsin, Hogeboom moved to the National Cancer Institute, and Claude went back to Belgium in 1949 to assume the directorship of the Jules Bordet Institute. Only Porter and I remained at The Rockefeller Institute; two years later, upon Murphy's retirement, we became "orphans" and were adopted by Herbert Gasser then the director of the Institute, since none of us had the rank required to head a laboratory.
Around that time, I started working in electron microscopy with the general aim of developing preparation procedures applicable to organized tissue. This line of research had been tackled before by a few investigators, Claude included, but there was still ample room for improvement. Taking advantage of whatever techniques were already available, Porter and I worked out enough improvements in microtomy and tissue fixation to obtain preparations which, at least for a while, appeared satisfactory and gratifying. A period of intense activity and great excitement followed since the new layer of biological structure revealed by electron microscopy proved to be unexpectedly rich and surprisingly uniform for practically all eukaryotic cells. Singly, or in collaboration with others, I did my share in exploring the newly open territory and, in the process, I defined the fine structure of mitochondria, and described the small particulate component of the cytoplasm (later called ribosomes); with Porter, I investigated the local differentiations of the endoplasmic reticulum and with Sanford Palay I worked out the fine structure of chemical synapses. With all this activity, our laboratory became reasonably well known and started functioning as a training center for biological electron microscopy. The circumstances that permitted this development were unusually favorable: we didn't have to worry about research funds (since we were well supported by Herbert Gasser), we had practically complete freedom in selecting our targets, strong competitors who kept us alert, and excellent collaborators who helped us in maintaining our advance.
In the middle 1950's, I felt that the time was ripe for going back to cell fractionation as a means of defining the chemical composition and the functional role of the newly discovered subcellular components. The intent was to use electron microscopy for monitoring cell fractionation. I was starting from structural findings and morphological criteria seemed appropriate for assessing the degree of homogeneity (or heterogeneity) of the cell fractions. Philip Siekevitz joined our laboratory in 1955 and together we showed that Claude's microsomes were fragments of the endoplasmic reticulum (as postulated by Claude in 1948) and that the ribosomes were ribonucleoprotein particles. To find out more about the function of the endoplasmic reticulum and of the attached ribosomes, we started an integrated morphological and biochemical analysis of the secretory process in the guinea pig pancreas.
In 1961, Keith Porter who had been the head of our group since 1953 joined the Biological Laboratories of Harvard University and, with his departure, the history of the second "Rockefeller group" came to an end. It was during this period that cell biology became a recognized field of research in biological sciences and that the Journal of Cell Biology and the American Society for Cell Biology were founded. Our group participated actively in each of these developments.
In the 1960's, I continued the work on the secretory process using in parallel or in succession two different approaches. The first relied exclusively on cell fractionation, and was developed in collaboration with Philip Siekevitz, Lewis Greene, Colvin Redman, David Sabatini and Yutaka Tashiro; it led to the characterization of the zymogen granules and to the discovery of the segregation of secretory products in the cisternal space of the endoplasmic reticulum. The second approach relied primarly on radioautography, and involved experiments on intact animals or pancreatic slices which were carried out in collaboration with Lucien Caro and especially James Jamieson. This series of investigations produced a good part of our current ideas on the synthesis and intracellular processing of proteins for export. A critical review of this line of research is presented in the Nobel Lecture.
In parallel with the work on the secretory process in the pancreatic exocrine cell, I maintained an interest in the structural aspects of capillary permeability, that goes back to the early 1950's when I found a large population of plasmalemmal vesicles in the endothelial cells of blood capillaries. Along this line of research, Marilyn Farquhar and I investigated the capillaries of the renal glomeruli and recognized that, in their case, the basement membrane is the filtration barrier for molecules of 100A diameter or larger; a byproduct of this work was the definition of junctional complexes in a variety of epithelia. Visceral (fenestrated) capillaries were investigated with Francesco Clementi, and muscular capillaries with Romaine Bruns and Nicolae and Maia Simionescu.
The capillary work has relied primarily on the use of "probe" molecules of known dimensions detected individually or in mass (after cytochemical reactions) by electron microscopy. It led to the identification of the passageways followed by large water-soluble molecules in both types of capillaries and by small molecules in visceral capillaries. The pathway followed by small, watersoluble molecules in muscular capillaries is still under investigation.
In the middle of the 1960's our laboratory began a series of investigations on membrane biogenesis in eukaryotic cells using as model objects either the endoplasmic reticulum of mammalian hepatocytes (with P. Siekevitz, Gustav Dallner and Andrea Leskes), or the thylakoid membranes of a green alga (Chlamydomonas reinhardtii) (With P. Siekevitz, Kenneth Hoober and Itzhak Ohad). These studies showed that "new" membrane is produced by expansion of "old" preexisting membrane (there is no de novo membrane assembly), and that new molecules are asynchronously inserted, and randomly distributed throughout the expanding membrane. Asynchrony also applies to the turnover of membrane proteins in the endoplasmic reticulum as shown by work down with P. Siekevitz, Tsuneo Omura and Walter Bock.
In 1973, I left the Rockefeller University to join the Yale University Medical School. The main reason for the move was my belief that the time had come for fruitful interactions between the new discipline of Cell Biology and the traditional fields of interest of medical schools, namely Pathology and Clinical Medicine. Besides, my work at the Rockefeller University was done: when I left there were at least five other laboratories working in different sectors of cell biology.
At present I am investigating, together with my collaborators, the interactions which occur among the membranes of the various compartments of the secertory pathway, namely the endoplasmic reticulum, the Golgi complex, the secretion granules, and the plasmalemma.
I have been a member of the National Academy of Sciences (U.S.A.) since 1961, and I have received in the past a number of awards and prizes for my scientific work, among them: the Lasker Award (1966), the Gairdner Special Award (1967), and the Hurwitz Prize - shared with Albert Claude and Keith Porter (1970).
Since my high school years I have been interested in history, especially in Roman history, a topic on which I have read rather extensively. The Latin that goes with this kind of interest proved useful when I had to generate a few terms and names for cell biology.
I have a daughter, Georgia Palade Van Duzen, and a son Philip Palade from a first marriage with Irina Malaxa, now deceased. In 1970 I married Marilyn Gist Farquhar who is a cell biologist like myself.
From Les Prix Nobel en 1974, Editor Wilhelm Odelberg, [Nobel Foundation], Stockholm, 1975
This autobiography/biography was written at the time of the award and later published in the book series Les Prix Nobel/Nobel Lectures. The information is sometimes updated with an addendum submitted by the Laureate.
George E. Palade died on 7 October, 2008.
Copyright © The Nobel Foundation 1974
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