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Structure and Function at the Cellular Level FREE

George E. Palade, MD
[+] Author Affiliations

Reprint requests to Rockefeller University, New York 10021 (Dr. Palade).


From Rockefeller University, New York. Presented as a 1966 Albert Lasker Basic Research Award Lecture at the New York University Medical Center, New York, Nov 17, 1966.


JAMA. 1966;198(8):815-825. doi:10.1001/jama.1966.03110210065024
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In the early 1950's, a series of improvements in preparation procedures made possible the full-scale application of electron microscopy to the study of cells and tissues. That was about 25 years after research had started in electron optics1 and about 15 years after electron microscopes had become available for research.2,3 The long lag gives an idea about the magnitude of the difficulties encountered in working out such procedures as well as about the important role played by appropriate techniques in research progress.

Once secured, these technical improvements opened for investigation a new and rich layer of biological organization which stretched from the limit of resolution of the light microscope, ie, about 0.2μ, to that of the electron microscope. The latter has reached at present about 5 angstroms and is still progressing. From one microscope to another there is, therefore, a gain of about 400 times in the ability

REFERENCES

Busch. H.:  Berechnung der Bahn von Kathodenstrahlen im axialsymmetrischen elektromagnetischen Felde , Ann Physik 81: 974, 1926;.
Knoll, M., and Ruska, E.:  Beitrag zur geometrischen Elektronenoptik: I , Ann Physik 12:607-640 ( (Feb) ) 1932;.
von Borries, B., and Ruska, E.:  Aufbau und Leistung des Siemens-Uebermikroskopes . Z Wiss Mikr 56:317-333 ( (Jan) ) 1939;.
Palade, G.E.:  The Organization of Living Matter , Proc Nat Acad Sci USA 52:613-634 ( (Aug) ) 1964;.
Palade, G.E.:  An Electron Microscopical Study of the Mitochondrial Structure , J Histochem Cytochem 1:188-211 ( (July) ) 1953;.
Palade, G.E., and Porter, K.R.:  Studies on the Endoplasmic Reticulum: I. Its Identification of Cells in situ , J Exp Med 100: 641-656 ( (Dec) ) 1954;.
Palade, G.E.:  The Endoplasmic Reticulum , J Biophys Biochem Cytol 2( (suppl) ):85-98 (Jan) 1956;.
Claude, A.; Porter, K.R.; and Fullam, E.F.:  A Study of Tissue Culture Cells by Electron Microscopy: Methods and Preliminary Observations , J Exp Med 81:233-246 ( (March) ) 1945;.
Porter, K.R.:  Observations on a Submicroscopic Basophilic Component of Cytoplasm , J Exp Med 97:727-750 ( (May) ) 1953;.
Palade, G.E.:  A Small Particulate Component of the Cytoplasm , J Biophys Biochem Cytol 1:59-68 ( (Jan) ) 1955;.
Claude, A.:  Studies on Cells: Morphology, Chemical Constitution, and Distribution of Biochemical Functions , Harvey Lect 48:121-164, 1947;-1948.
Hogeboom, G.H.; Schneider, W.C.; and Palade, G.E.:  Cytochemical Studies of Mammalian Tissues: I. The Isolation of Intact Mitochondria From Rat Liver; Some Biochemical Properties of Mitochondria and Submicroscopic Particulate Material , J Biol Chem 172:619-636 ( (Feb) ) 1948;.
Lehninger, A.L.: The Mitochondrion: Molecular Basis of Structure and Function , New York: W. A. Benjamin Inc., 1964;.
Siekevitz, P.:  Uptake of Radioactive Alanine in vitro Into the Proteins of Rat Liver Fractions , J Biol Chem 195:549-565 ( (April) ) 1952;.
Palade, G.E., and Siekevitz, P.:  Liver Microsomes: An Integrated Morphological and Biochemical Study , J Biophys Biochem Cytol 2:171-200 ( (March) ) 1956;.
Palade, G.E.: " Microsomes and Ribonucleoprotein Particles ," in Roberts, R.B. (ed.): Microsomal Particles and Protein Synthesis , New York: Pergamon Press, Inc., 1958;, pp 36-61.
Ernster, L.; Siekevitz, P.; and Palade, G.E.:  Enzyme-Structure Relationship in the Endoplasmic Reticulum of Rat Liver, A Morphological and Biochemical Study , J Cell Biol 15:541-562 ( (Dec) ) 1962;.
Palade, G.E., and Siekevitz, P.:  Pancreas Microsomes: An Integrated Morphological and Biochemical Study , J Biophys Biochem Cytol 2:671-690 ( (Nov) ) 1956;.
Petermann, M.L., and Hamilton, M.G.:  An Ultracentrifugal Analysis of the Macromolecular Particles of Normal and Leukemic Mouse Spleen , Cancer Res 12:373-378 ( (May) ) 1952;.
Petermann, M.L.; Mizen, N.A.; and Hamilton, M.G.:  The Macromolecular Particles of Normal and Regenerating Rat Liver , Cancer Res 13:372-375 ( (May) ) 1953;.
Roberts, R.B.: " Introduction ," in Roberts, R.B. (ed.): Microsomal Particles and Protein Synthesis , New York: Pergamon Press, Inc., 1958;, pp vii-viii.
Zamecnik, P.C.:  Historical and Current Aspects of the Problem of Protein Synthesis , Harvey Lect 54:256-281, 1958;-1959.
Kirsch, J.F.; Siekevitz, P.; and Palade, G.E.:  Amino Acid Incorporation in vitro by Ribonucleoprotein Particles Detached From Guinea Pig Liver Microsomes , J Biol Chem 235:1419-1424 ( (May) ) 1960;.
Harris, R.J.C. (ed.): Protein Biosynthesis , New York: Academic Press, Inc., 1961;, pp 1-409.
Jacob, F., and Monod, J.:  Genetic Regulatory Mechanisms in the Synthesis of Proteins , J Molec Biol 3:318-356 ( (June) ) 1961;.
Warner, J.R.; Rich, A.; and Hall, C.E.:  Electron Microscope Studies of Ribosomal Clusters Synthesizing Protein , Science 138: 1399-1403 ( (Dec) ) 1962;.
Palay, S.L., and Palade, G.E.:  The Fine Structure of Neurons . J Biophys Biochem Cytol 1:69-88 ( (Jan) ) 1955;.
Siekevitz, P., and Palade, G.E.:  A Cytochemical Study of the Pancreas of the Guinea Pig: I. Isolation and Enzymic Activities of Cell Fractions , J Biophys Biochem Cytol 4:203-218 ( (March) ) 1958;.
Siekevitz, P., and Palade, G.E.:  A Cytochemical Study of the Pancreas of the Guinea Pig: II. Functional Variation in the Enzymatic Activities of Microsomes , J Biophys Biochem Cytol 4:309-318 ( (May) ) 1958;.
Palade, G.E.:  Intracisternal Granules in the Exocrine Cell of the Pancreas , J Biophys Biochem Cytol 2:417-422 ( (July) ) 1956;.
Palade, G.E.; Siekevitz, P.; and Caro, L.G.: " Structure, Chemistry and Function of the Pancreatic Exocrine Cell ," in de Reuck, A.V.S., and Cameron, M.P. (eds.): Ciba Foundation Symposium on the Exocrine Pancreas , London: J. & A. Churchill Ltd., 1962;, pp 23-49.
Siekevitz, P., and Palade, G.E.:  A Cytochemical Study of 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 7:619-630 ( (July) ) 1960;.
Palay, S.L.: " The Morphology of Secretion ," in Palay, S.L. (ed.): Frontiers in Cytology , New Haven, Conn: Yale University Press, 1958;, pp 305-342.
Sjöstrand, F.S.: " The Fine Structure of the Exocrine Pancreas Cells ," in de Reuck, A.V.S., and Cameron, M.P. (eds.): Ciba Foundation Symposium on the Exocrine Pancreas , London: J. & A. Churchill Ltd., 1962;, pp 1-22.
Caro, L.G., and van Tubergen, R.P.:  High Resolution Autoradiography: I. Methods , J Cell Biol 15:173-199 ( (Nov) ) 1962;.
Caro, L.G., and Palade, G.E.:  Protein Synthesis, Storage and Discharge in the Pancreatic Exocrine Cell: An Autoradiographic Study , J Cell Biol 20:473-495 ( (March) ) 1964;.
Greene, L.J.; Hirs, C.H.W.; and Palade, G.E.:  On the Protein Composition of Bovine Pancreatic Zymogen Granules . J Biol Chem 238:2054-2070 ( (June) ) 1963;.
Palade, G.E.: " Functional Changes in the Structure of Cell Components ," in Hayashi, T. (ed.): Subcellular Particles , New York: Ronald Press Co., 1959;, pp 64-80.
Redman, C.M.; Siekevitz, P.; and Palade, G.E.:  Synthesis and Transfer of Amylase in Pigeon Pancreatic Microsomes , J Biol Chem 241:1150-1158 ( (May) ) 1966;.
Weiss, S.B.; Acs, G.; and Lipmann, F.:  Amino Acid Incorporation in Pigeon Pancreas Fractions , Proc Nat Acad Sci USA 44:189-196 ( (Feb) ) 1958;.
Redman, C., and Sabatini, D.:  Vectorial Discharge of Peptides Released by Puromycin From Attached Ribosomes , Proc Nat Acad Sci USA 56:608-615 ( (Aug) ) 1966;.
Jamieson, J.D., and Palade, G.E.:  Role of the Golgi Complex in the Intracellular Transport of Secretory Proteins , Proc Nat Acad Sci USA 55:424-431 ( (Feb) ) 1966;.
Essner, E., and Novikoff, A.B.:  Cytological Studies on Two Functional Hepatomas , J Cell Biol 15:289-311 ( (Nov) ) 1962;.
Dallner, G.; Siekevitz, P.; and Palade, G.E.:  Biogenesis of Endoplasmic Reticulum Membranes: I. Structural and Chemical Differentiation in Developing Rat Hepatocytes; II. Synthesis of Constitutive Microsomal Enzymes in Developing Rat Hepatocytes , J Cell Biol 30:73-96; 97-117 ( (July) ) 1966;.

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Busch. H.:  Berechnung der Bahn von Kathodenstrahlen im axialsymmetrischen elektromagnetischen Felde , Ann Physik 81: 974, 1926;.
Knoll, M., and Ruska, E.:  Beitrag zur geometrischen Elektronenoptik: I , Ann Physik 12:607-640 ( (Feb) ) 1932;.
von Borries, B., and Ruska, E.:  Aufbau und Leistung des Siemens-Uebermikroskopes . Z Wiss Mikr 56:317-333 ( (Jan) ) 1939;.
Palade, G.E.:  The Organization of Living Matter , Proc Nat Acad Sci USA 52:613-634 ( (Aug) ) 1964;.
Palade, G.E.:  An Electron Microscopical Study of the Mitochondrial Structure , J Histochem Cytochem 1:188-211 ( (July) ) 1953;.
Palade, G.E., and Porter, K.R.:  Studies on the Endoplasmic Reticulum: I. Its Identification of Cells in situ , J Exp Med 100: 641-656 ( (Dec) ) 1954;.
Palade, G.E.:  The Endoplasmic Reticulum , J Biophys Biochem Cytol 2( (suppl) ):85-98 (Jan) 1956;.
Claude, A.; Porter, K.R.; and Fullam, E.F.:  A Study of Tissue Culture Cells by Electron Microscopy: Methods and Preliminary Observations , J Exp Med 81:233-246 ( (March) ) 1945;.
Porter, K.R.:  Observations on a Submicroscopic Basophilic Component of Cytoplasm , J Exp Med 97:727-750 ( (May) ) 1953;.
Palade, G.E.:  A Small Particulate Component of the Cytoplasm , J Biophys Biochem Cytol 1:59-68 ( (Jan) ) 1955;.
Claude, A.:  Studies on Cells: Morphology, Chemical Constitution, and Distribution of Biochemical Functions , Harvey Lect 48:121-164, 1947;-1948.
Hogeboom, G.H.; Schneider, W.C.; and Palade, G.E.:  Cytochemical Studies of Mammalian Tissues: I. The Isolation of Intact Mitochondria From Rat Liver; Some Biochemical Properties of Mitochondria and Submicroscopic Particulate Material , J Biol Chem 172:619-636 ( (Feb) ) 1948;.
Lehninger, A.L.: The Mitochondrion: Molecular Basis of Structure and Function , New York: W. A. Benjamin Inc., 1964;.
Siekevitz, P.:  Uptake of Radioactive Alanine in vitro Into the Proteins of Rat Liver Fractions , J Biol Chem 195:549-565 ( (April) ) 1952;.
Palade, G.E., and Siekevitz, P.:  Liver Microsomes: An Integrated Morphological and Biochemical Study , J Biophys Biochem Cytol 2:171-200 ( (March) ) 1956;.
Palade, G.E.: " Microsomes and Ribonucleoprotein Particles ," in Roberts, R.B. (ed.): Microsomal Particles and Protein Synthesis , New York: Pergamon Press, Inc., 1958;, pp 36-61.
Ernster, L.; Siekevitz, P.; and Palade, G.E.:  Enzyme-Structure Relationship in the Endoplasmic Reticulum of Rat Liver, A Morphological and Biochemical Study , J Cell Biol 15:541-562 ( (Dec) ) 1962;.
Palade, G.E., and Siekevitz, P.:  Pancreas Microsomes: An Integrated Morphological and Biochemical Study , J Biophys Biochem Cytol 2:671-690 ( (Nov) ) 1956;.
Petermann, M.L., and Hamilton, M.G.:  An Ultracentrifugal Analysis of the Macromolecular Particles of Normal and Leukemic Mouse Spleen , Cancer Res 12:373-378 ( (May) ) 1952;.
Petermann, M.L.; Mizen, N.A.; and Hamilton, M.G.:  The Macromolecular Particles of Normal and Regenerating Rat Liver , Cancer Res 13:372-375 ( (May) ) 1953;.
Roberts, R.B.: " Introduction ," in Roberts, R.B. (ed.): Microsomal Particles and Protein Synthesis , New York: Pergamon Press, Inc., 1958;, pp vii-viii.
Zamecnik, P.C.:  Historical and Current Aspects of the Problem of Protein Synthesis , Harvey Lect 54:256-281, 1958;-1959.
Kirsch, J.F.; Siekevitz, P.; and Palade, G.E.:  Amino Acid Incorporation in vitro by Ribonucleoprotein Particles Detached From Guinea Pig Liver Microsomes , J Biol Chem 235:1419-1424 ( (May) ) 1960;.
Harris, R.J.C. (ed.): Protein Biosynthesis , New York: Academic Press, Inc., 1961;, pp 1-409.
Jacob, F., and Monod, J.:  Genetic Regulatory Mechanisms in the Synthesis of Proteins , J Molec Biol 3:318-356 ( (June) ) 1961;.
Warner, J.R.; Rich, A.; and Hall, C.E.:  Electron Microscope Studies of Ribosomal Clusters Synthesizing Protein , Science 138: 1399-1403 ( (Dec) ) 1962;.
Palay, S.L., and Palade, G.E.:  The Fine Structure of Neurons . J Biophys Biochem Cytol 1:69-88 ( (Jan) ) 1955;.
Siekevitz, P., and Palade, G.E.:  A Cytochemical Study of the Pancreas of the Guinea Pig: I. Isolation and Enzymic Activities of Cell Fractions , J Biophys Biochem Cytol 4:203-218 ( (March) ) 1958;.
Siekevitz, P., and Palade, G.E.:  A Cytochemical Study of the Pancreas of the Guinea Pig: II. Functional Variation in the Enzymatic Activities of Microsomes , J Biophys Biochem Cytol 4:309-318 ( (May) ) 1958;.
Palade, G.E.:  Intracisternal Granules in the Exocrine Cell of the Pancreas , J Biophys Biochem Cytol 2:417-422 ( (July) ) 1956;.
Palade, G.E.; Siekevitz, P.; and Caro, L.G.: " Structure, Chemistry and Function of the Pancreatic Exocrine Cell ," in de Reuck, A.V.S., and Cameron, M.P. (eds.): Ciba Foundation Symposium on the Exocrine Pancreas , London: J. & A. Churchill Ltd., 1962;, pp 23-49.
Siekevitz, P., and Palade, G.E.:  A Cytochemical Study of 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 7:619-630 ( (July) ) 1960;.
Palay, S.L.: " The Morphology of Secretion ," in Palay, S.L. (ed.): Frontiers in Cytology , New Haven, Conn: Yale University Press, 1958;, pp 305-342.
Sjöstrand, F.S.: " The Fine Structure of the Exocrine Pancreas Cells ," in de Reuck, A.V.S., and Cameron, M.P. (eds.): Ciba Foundation Symposium on the Exocrine Pancreas , London: J. & A. Churchill Ltd., 1962;, pp 1-22.
Caro, L.G., and van Tubergen, R.P.:  High Resolution Autoradiography: I. Methods , J Cell Biol 15:173-199 ( (Nov) ) 1962;.
Caro, L.G., and Palade, G.E.:  Protein Synthesis, Storage and Discharge in the Pancreatic Exocrine Cell: An Autoradiographic Study , J Cell Biol 20:473-495 ( (March) ) 1964;.
Greene, L.J.; Hirs, C.H.W.; and Palade, G.E.:  On the Protein Composition of Bovine Pancreatic Zymogen Granules . J Biol Chem 238:2054-2070 ( (June) ) 1963;.
Palade, G.E.: " Functional Changes in the Structure of Cell Components ," in Hayashi, T. (ed.): Subcellular Particles , New York: Ronald Press Co., 1959;, pp 64-80.
Redman, C.M.; Siekevitz, P.; and Palade, G.E.:  Synthesis and Transfer of Amylase in Pigeon Pancreatic Microsomes , J Biol Chem 241:1150-1158 ( (May) ) 1966;.
Weiss, S.B.; Acs, G.; and Lipmann, F.:  Amino Acid Incorporation in Pigeon Pancreas Fractions , Proc Nat Acad Sci USA 44:189-196 ( (Feb) ) 1958;.
Redman, C., and Sabatini, D.:  Vectorial Discharge of Peptides Released by Puromycin From Attached Ribosomes , Proc Nat Acad Sci USA 56:608-615 ( (Aug) ) 1966;.
Jamieson, J.D., and Palade, G.E.:  Role of the Golgi Complex in the Intracellular Transport of Secretory Proteins , Proc Nat Acad Sci USA 55:424-431 ( (Feb) ) 1966;.
Essner, E., and Novikoff, A.B.:  Cytological Studies on Two Functional Hepatomas , J Cell Biol 15:289-311 ( (Nov) ) 1962;.
Dallner, G.; Siekevitz, P.; and Palade, G.E.:  Biogenesis of Endoplasmic Reticulum Membranes: I. Structural and Chemical Differentiation in Developing Rat Hepatocytes; II. Synthesis of Constitutive Microsomal Enzymes in Developing Rat Hepatocytes , J Cell Biol 30:73-96; 97-117 ( (July) ) 1966;.
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