A Life for Nobel Prize, Remember George Emil Palade
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REVIEW ARTICLES REVIEW –A LIFE FOR NOBEL PRIZE, REMEMBER GEORGE EMIL PALADE Mirela E. CADAR* and Mircea GABOREANU Faculty of Animal Science and Biotechnologies, University of Agricultural Sciences and Veterinary Medicine, 3-5 Mănăştur Street, 400372 Cluj-Napoca, Romania *Corresponding author, email: [email protected] Bulletin UASVM Animal Science and Biotechnologies 71(2) / 2014, Print ISSN 1843-5262; Electronic ISSN 1843-536X DOI: 10.15835/buasvmcn-asb:10484 Abstract Four decades ago, the Nobel Prize for Medicine and Physiology honored and rewarded the activity in Cellular and Molecular Biology domain of three researchers, Albert Claude (1899-1983), Christian De Duve (1917-2013) and George Emil Palade (1912-2008). Viewing the life and activity history of GE Palade comes out his respect for a certain research ethics and his demeanor for his very numerous collaborators and disciples. Keywords: cellular biology, molecular biology, Nobel Prize, GE Palade INTRODUCTION biochemistry and anatomy. His PhD thesis was of Four decades ago, the Nobel Prize for Medicine anatomy domain with the theme “The nephron of and Physiology honored and rewarded the activity cetacean Delphinus delphi”. in Cellular and Molecular Biology domain of three After university graduation, GE Palade wor- researchers, two Belgians –Albert Claude (1899- ked for a short time as assistant in the Clinic 1983) and Christian De Duve (1917-2013) and of Internal Diseases, and than he returned at an American of Romanian origin –George Emil Anatomy Discipline, where in few years became Palade (1912-2008). The motivation of Nobel assistant, lecturer and associated professor. Committee was “For discoveries concerning the The chief of Anatomy Discipline was Professor functional organization of the cell that were seminal Grigore T. Popa, which in 1930 during a research events in the development of modern cell biology”. stage at Cambridge University has discovered and described with Unna Fielding the hypophysial 1912, Iaşi Romania portal vessel system. GE Palade was born in November 19, 1912 in GE Palade married in 1944 Irina Malaxa, Iaşi, Romania, in a family in which both parents physician and daughter of Nicolae Malaxa –the (father Ioan Emil Palade, 1885-1961 and mother magnate of heavy Romanian industry. In 1945 was Constanţa Cantemir Palade, 1886-1976) and born Georgia, the irst child, and the second one also grandparents had intellectual professions Philip, will be born in 1957 in USA. (professors, schoolteachers, reverends). GE Palade had two sisters, Adriana who became Geography 1946, New York USA teacher and Constanţa, pediatric physician. In 1946, GE Palade with his wife and daughter emigrated in USA, with the wish to continue their 1940, Bucharest Romania studies. Having a letter of introduction from After graduation of high school in 1929, GE professor Grigore T. Popa to Robert Chambers Palade was admitted at Carol Davila School of from New York University, Department of Biology, Medicine from Bucharest, Romania and received GE Palade was accepted as “Visiting Investigator”. his MD in 1940. During the irst university Here, during few months, he continued his years, GE Palade revealed a special interest for morpho-functional study of kidney, for this time 78 CADAR et al on in vitro cultures of renal tissue from chicken Sanford Palay, the botanist Ruth Sager and a long- embryos, and the results guiding to his irst distance collaborator (from 1954 until 1961) the published article in USA in 1947. In the same biochemist Philip Siekevitz, all together forming year, being invited by Albert Claude, GE Palade “the second Rockefeller group”. goes to Rockefeller Institute for Medical Research, During the activity of this group, GE Palade where he will stay 25 years. There, Albert Claude described for the irst time the structure of had also as collaborators the naturalist Keith mitochondrion with all its aspects from different Porter, the physician George Hogeboom and the cellular type, named cristae mitochondriales biochemist Walter Schneider. The preoccupations the prolongations inside them and demonstrated of this researchers’ group, which GE Palade named that mitochondria are permanent organelles in “the irst Rockefeller group”, were focused mainly cytoplasm of all eukaryotic cells. in two directions: cell fractionation for organelle When he published these data, GE Palade be- separation and their biochemical analysis and bio- came a naturalized American citizen. lo gical sample examination in electronic micro- Together with Keith Porter, GE Palade continued scope. the study of endoplasmic reticulum, for this time Albert Claude initiated cell fractionation and on ultraine slides, describing its two aspects: ultracentrifugation of cellular homogenate since rough or granular endoplasmic reticulum and 1940, and he succeeded to isolate only small smooth or agranular endoplasmic reticulum. vesicular structures, named microsomes. They studied the same organelle in muscular GE Palade improved this technique perfor- ibers and named it sarcoplasmic reticulum. mance conceiving the procedure known as GE Palade with Philip Siekevitz had demons- “ultracentrifugation in sucrose density gradient”. trated that cytoplasmic subcellular structures Albert Claude with Keith Porter used for the described by Keith Porter and named microsomes, irst time in 1947 an electronic microscope of are in reality vesicular fragments derived from industrial type for cell study. Examining a single- endoplasmic reticulum during cells’ fractioning. layer cell culture they described in cells’ very thin But, one of the most important discoveries cytoplasm a structure with lace aspect, vaguely of GE Palade was that of cytoplasmic structures, contoured, which was named endoplasmic which he named “small granular components of reticulum. cytoplasm” being either free in cytosol, isolated In Rockefeller Institute the irst electronic or grouped or attached to endoplasmic reticulum microscope was made in function in 1948. It use surface. These structures were subsequently in biological research imposed ultraine sections, named granules of Palade, ribonucleoproteic thick of only 50-150 nm, and a more correct particles, and nowadays are named ribosomes. chemical ixation of subcellular structures, which The study of endoplasmic reticulum and allows obtaining optimal resolution on images. ribosomes was continued as biochemical one, in These dificulties were surpassed when was collaboration with Philip Siekevitz. Were developed invented the ultramicrotome by Keith Porter and experiments with tracer atom aminoacids marked Johan Blum and the ixation method of biological with radioactive isotopes concluding that these samples with a osmium tetraoxyde buffered with cytoplasmic structures have as main function the sodium veronal at 7.0-7.5 pH, conceived by GE protein synthesis. Palade and known as “ixative of Palade”. In same period GE Palade, having as labora- With these means, “the irst Rockefeller group” tory chief the neurophysiologist Herbert Gasser achieved the isolation of mitochondria from (Nobel Prize 1944) targeted his researches hepatocytes (1947), their cytochemistry and also on electrono-microscopic study of nervous demonstration of Golgi apparatus presence in tissue. For the irst time there were marked out somatic cells (1949). the nervous fibers of C type leading the pain In 1949, the researchers’ group from sensation, and was named the mesaxon as an Rockefeller Institute diminished by departure annexed structure of them. The collaboration with of Albert Claude, Walter Schneider and George Sanford Palay, also neurophysiologist, gave to GE Hogeboom, but with Keith Porter and GE Palade Palade the opportunity to demonstrate the fact came the neurophysiologists Herbert Gasser and that Nissl bodies or granulations from optical Bulletin UASVM Animal Science and Biotechnologies 71(2) / 2014 Review –A life for Nobel Prize, remember George Emil Palade 79 microscopy are in electron microscope dense Blobel. Starting 1978, there came also 14 post- packs of lattened sacks of granular endoplasmic doctoral physicians, geneticists and biochemists reticulum. GE Palade was also those one who irst from Romania. In next 12 years of activity, the described the inter-neuronal and neuromuscular main preoccupations of GE Palade with mentioned synapse ultrastructure, with the two portions, collaborators were: the intracellular aspects of pre- and post-synaptic elements, the presence of protein secretion process, the ultrastructure of synaptic vesicles and existence of synaptic cleft, endothelium of blood capillaries, the mechanisms thus demonstrating the contiguity relation and of capillaries’ permeability and cytomembrane not continuity one between neurons. biogenesis. Collaboration with the botanist Ruth Sager During 1962-1964, GE Palade in collaboration leaded to study the chloroplast ultrastructure with Lars Ernster, Lewis Joel Green, Johan Kirsch, from green algae, thus demonstrating that be side Colvin Redman, Gustav Dallner, Any Leskes and them, in vegetal cells, is also present the endoplas- more often with Lucien Caro and James Jamieson mic reticulum. effected majority of experiments through of were In 1957, GE Palade in collaboration with proved the protein secretion phases in glandular the anatomist Benet Russel conceived the me- cells of exocrine pancreas, both in vivo and in thod with potassium telurit to make evident vitro. In this study unless electron microscopic dehydrogenases’ activity in electron microscope,