DOCSLIB.ORG

George Emil Palade (1912-2008)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
George Emil Palade (1912-2008) YALE JOURNAL OF BIOLOGY AND MEDICINE 84 (2011), pp.113-116. Copyright © 2011. FOCUS: YALE SCHOOL OF MEDICINE BICENTENNIAL the Legacy of a Founding Father of Modern cell Biology: George Emil Palade (1912-2008) Suzana M. Zorca, MD, a and Cornelia E. Zorca b* aDepartment of Anesthesiology, Yale-New Haven Hospital, New Haven, Connecticut, and bDepartment of Genetics, Yale School of Medicine, New Haven, Connecticut George Emil Palade’s scientific contributions significantly advanced the field of modern cell biology. He pioneered a multidisciplinary approach, combining cell fractionation, biochem - istry, and electron microscopy, which led to the identification of the ribosome as the site of protein synthesis and elucidated the eukaryotic secretory pathway. For these accomplish - ments, Palade, along with Albert Claude and Christian de Duve, won the 1974 Nobel Prize in Physiology or Medicine. This article provides an overview of Palade’s seminal research in the context of the early developments in the field. introduction toral thesis on the “microscopic anatomy” George Emil Palade (Figure 1) was of the dolphin nephron [1]. In studying this born in Iasi, Romania, in 1912 and was the unique topic, he developed an understand - son of a philosophy professor and an edu - ing of the functional adaptation of mam - cator. Early in his life, he chose to pursue mals to marine life. This early academic medicine because of its focus on the “tan - work occurred during the politically tense gibles and specifics” [1] of physiology and years leading up to World War II. Recall - the scientific method. However, his inter - ing the social and political turmoil sweep - ests were remarkably diverse, and he in - ing through Europe in the pre-war era, herited a deep-seated respect for Palade noted, “. the continent was torn philosophy and rational inquiry from his apart by all kinds of ideological move - early upbringing. At the age of 18, he ma - ments. This state of insecurity had [a] sig - triculated at the University of Medicine of nificant impact during my studies” [2]. The Bucharest and in 1940 completed his doc - young Palade served in the medical corps *To whom all correspondence should be addressed: Cornelia E. Zorca, Department of Genetics, Yale School of Medicine, 300 Cedar Street, P.O. Box 208011, New Haven, CT 06520; Tele: 203-785-5383; Email: [email protected]. †Abbreviations: NYU, New York University; EM, electron microscopy; RNA, ribonucleic acid; ER, endoplasmic reticulum; RNP, ribonucleoprotein; ATP, adenosine triphosphate; UCSD, University of California, San Diego. 113 114 Zorca: Legacy of George Palade of the Romanian Army. Upon his return from the war, he became a faculty member of the Institute of Anatomy at his alma mater and remained there until 1946. In 1946, Palade moved to the United States to pursue postdoctoral studies in the laboratory of Robert Chambers at New York University (NYU). Shortly thereafter, Palade met Albert Claude after a lecture Claude gave at NYU concerning electron microscopy. Palade became intrigued by the potential of this technique to reveal the cel - lular and sub-cellular organization of tissues and joined Claude at the Rockefeller Insti - tute for Medical Research in the fall of 1946 [1]. Together with Claude, George Hogeboom, and Walter Schneider, Palade developed the sucrose method for tissue fractionation and subsequently optimized tissue fixation with buffered osmium tetrox - Figure 1. dr. George Palade . 1974 Nobel ide for electron microscopy (EM) structural Prize Laureate in Physiology or Medicine. studies [1,3]. These two advances, described Photograph courtesy of Dr. James D. Jamieson in more detail below, were instrumental in Palade’s landmark discovery of “. a small homogenized in saline or water [3]. By sub - particulate component of the cytoplasm jecting the liver tissue homogenates to se - (later called ribosome)” [1]. quential high-speed centrifugation steps, As he progressed from Assistant Pro - Claude isolated three morphologically dis - fessor to head of the Laboratory of Cell Bi - tinct fractions: a large granule fraction con - ology at the Rockefeller Institute, Palade’s sisting of mitochondria, a ribonucleic acid research focus shifted toward elucidating the (RNA)-rich microsome fraction, and a solu - pathway of protein synthesis and secretion. ble fraction [3,4]. Palade further developed With a unique “. ability to link the most this tool by using hypertonic sucrose for ho - disparate observations into a coherent and mogenization and cell fractionation. His ap - testable working hypothesis” [4], he pursued proach improved the preservation of critical questions involving sub-cellular tis - organelle morphology compared to the use sue organization and protein trafficking. Ef - of saline or water, which led to aggregation fortlessly, he passed on his passion for and swelling [1,3]. Furthermore, sucrose- in-depth scientific dissection of physiologi - gradient centrifugation (based on density cal pathways to numerous students and post - differences of sub-cellular components) fa - doctoral fellows [4]. His work on the cilitated the isolation of increasingly pure secretory pathway constitutes a central com - cell fractions. ponent of the field of modern cell biology. When Palade first began this work, electron microscopy was still in its infancy. Improvements in microtomy and embedding EArLY tEcHnicAL AdVAncES in yielded sections of suitable thinness, but the MicroScoPY And SuBcELLuLAr FrActionAtion fixation procedures used at that time often led to precipitation artifacts. Palade’s major Just a few years before Palade joined contribution was pioneering the use of Claude at the Rockefeller, Claude had used buffered osmium tetroxide as a fixative to differential centrifugation to separate intra - obtain improved contrast [1,4,5]. In the 1974 cellular components from guinea pig liver Nobel Prize presentation speech, Palade is Zorca: Legacy of George Palade 115 acknowledged as “. foremost among those Jamieson and Palade used pulse-chase label - who developed electron microscopy further, ing of secretory proteins in pancreatic tissue to the highest degree of artistry” [6]. With slices to visualize the secreted proteins as these early technical advances, Palade pro - grains in EM [7,11]. Following a short pulse ceeded to investigate the structure and func - with radioactive amino acids, Jamieson and tion of newly isolated organelles. Palade monitored the grains over a chase- time-course as they sequentially moved from the ribosomes of the rough ER to the Golgi A MuLtidiSciPLinArY APProAcH complex and then to zymogen granules be - to idEntiFY StructurE And Function fore reaching the plasma membrane. These results demonstrated for the first The hallmark of Palade’s research ap - time the role of the Golgi complex in pro - proach in the mid 1950s and 1960s was the tein trafficking [11,12]. Secondly, they integration of cell fractionation and EM data. showed that proteins were transported in Philip Siekevitz and Palade first demon - vesicles from one cellular compartment to strated that the “microsome fraction” con - the next, without mixing with the cytoplasm sisted of fragments of endoplasmic reticulum [7]. In addition, they demonstrated that in - (ER) [7,8]. Using detergent solubilization tracellular protein transport was adenosine followed by centrifugation, Siekevitz and triphosphate (ATP) dependent and that, in its Palade subsequently found that microsome absence, secretory proteins remained membranes consisted of ribonucleoprotein trapped in the rough ER [7,13]. Further - (RNP) particles [9,10]. These RNPs later be - more, Palade, Jamieson, and their cowork - came known as ribosomes. Through a series ers demonstrated that these principles of of elegant EM studies in pancreatic acinar protein transport were universally applica - cell preparations, Siekevitz and Palade ble to other cell types [7]. showed that ribosomes were the sites of new protein synthesis [9]. In tracing the fate of tHE LAtEr YEArS newly synthesized proteins with radioactive amino acids, Palade and Siekevitz showed Palade remained at the Rockefeller until that they accumulated in microsomal vesi - 1973, when he moved to Yale University be - cles [3,9]. This was the first demonstration cause of “[his] belief that the time had come of vectorial transport of nascent polypeptides for fruitful interactions between the new dis - across the ER membrane into the lumen. cipline of Cell Biology and the traditional fields of interest of medical schools, namely Pathology and Clinical Medicine” [1]. He trAcinG tHE SEcrEtorY established and chaired the Section of Cell PAtHWAY in tHE PAncrEAtic AcinAr cELL Biology and was Sterling Professor of Cell Biology from 1975 to 1983 [5]. He remained Palade’s studies of protein synthesis and at Yale until 1990, when he moved to the secretion in the pancreatic acinar cell proved University of California, San Diego to be particularly fruitful. This model cell (UCSD), where he founded the department type was ideal for these studies because it is of Cellular and Molecular Medicine and specialized for the secretion of digestive en - served as the Dean for Scientific Affairs at zymes, including lipase, amylase, and chy - the School of Medicine [5]. motrypsinogen [7]. Together with Lucien For his seminal contributions to the elu - Caro and James Jamieson, Palade developed cidation of secretory pathways and estab - radioautography, a method that could be used lishing the early foundations of
Load more

Recommended publications
  • RANDY SCHEKMAN Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, USA
    GENES AND PROTEINS THAT CONTROL THE SECRETORY PATHWAY Nobel Lecture, 7 December 2013 by RANDY SCHEKMAN Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, USA. Introduction George Palade shared the 1974 Nobel Prize with Albert Claude and Christian de Duve for their pioneering work in the characterization of organelles interrelated by the process of secretion in mammalian cells and tissues. These three scholars established the modern field of cell biology and the tools of cell fractionation and thin section transmission electron microscopy. It was Palade’s genius in particular that revealed the organization of the secretory pathway. He discovered the ribosome and showed that it was poised on the surface of the endoplasmic reticulum (ER) where it engaged in the vectorial translocation of newly synthesized secretory polypeptides (1). And in a most elegant and technically challenging investigation, his group employed radioactive amino acids in a pulse-chase regimen to show by autoradiograpic exposure of thin sections on a photographic emulsion that secretory proteins progress in sequence from the ER through the Golgi apparatus into secretory granules, which then discharge their cargo by membrane fusion at the cell surface (1). He documented the role of vesicles as carriers of cargo between compartments and he formulated the hypothesis that membranes template their own production rather than form by a process of de novo biogenesis (1). As a university student I was ignorant of the important developments in cell biology; however, I learned of Palade’s work during my first year of graduate school in the Stanford biochemistry department.
    [Show full text]
  • 書 名 等 発行年 出版社 受賞年 備考 N1 Ueber Das Zustandekommen Der
    書 名 等 発行年 出版社 受賞年 備考 Ueber das Zustandekommen der Diphtherie-immunitat und der Tetanus-Immunitat bei thieren / Emil Adolf N1 1890 Georg thieme 1901 von Behring N2 Diphtherie und tetanus immunitaet / Emil Adolf von Behring und Kitasato 19-- [Akitomo Matsuki] 1901 Malarial fever its cause, prevention and treatment containing full details for the use of travellers, University press of N3 1902 1902 sportsmen, soldiers, and residents in malarious places / by Ronald Ross liverpool Ueber die Anwendung von concentrirten chemischen Lichtstrahlen in der Medicin / von Prof. Dr. Niels N4 1899 F.C.W.Vogel 1903 Ryberg Finsen Mit 4 Abbildungen und 2 Tafeln Twenty-five years of objective study of the higher nervous activity (behaviour) of animals / Ivan N5 Petrovitch Pavlov ; translated and edited by W. Horsley Gantt ; with the collaboration of G. Volborth ; and c1928 International Publishing 1904 an introduction by Walter B. Cannon Conditioned reflexes : an investigation of the physiological activity of the cerebral cortex / by Ivan Oxford University N6 1927 1904 Petrovitch Pavlov ; translated and edited by G.V. Anrep Press N7 Die Ätiologie und die Bekämpfung der Tuberkulose / Robert Koch ; eingeleitet von M. Kirchner 1912 J.A.Barth 1905 N8 Neue Darstellung vom histologischen Bau des Centralnervensystems / von Santiago Ramón y Cajal 1893 Veit 1906 Traité des fiévres palustres : avec la description des microbes du paludisme / par Charles Louis Alphonse N9 1884 Octave Doin 1907 Laveran N10 Embryologie des Scorpions / von Ilya Ilyich Mechnikov 1870 Wilhelm Engelmann 1908 Immunität bei Infektionskrankheiten / Ilya Ilyich Mechnikov ; einzig autorisierte übersetzung von Julius N11 1902 Gustav Fischer 1908 Meyer Die experimentelle Chemotherapie der Spirillosen : Syphilis, Rückfallfieber, Hühnerspirillose, Frambösie / N12 1910 J.Springer 1908 von Paul Ehrlich und S.
    [Show full text]
  • Five Great Ideas of Biology
    GREATGREAT IDEASIDEAS OFOF BIOLOGYBIOLOGY Paul Nurse KITP Public Lecture, Feb 24, 2010 THETHE CELLCELL The basic unit of life ROBERTROBERT HOOKEHOOKE’’SS MICROSCOPEMICROSCOPE Cork Image: Past Present STEMSTEM IMAGES:IMAGES: PASTPAST ANDAND PRESENTPRESENT Nehemiah Grew (1682) ANTONIANTONI VANVAN LEEUWENHOEKLEEUWENHOEK MICROORGANISMSMICROORGANISMS VANVAN LEEUWENHOEK?LEEUWENHOEK? THEODORTHEODOR SCHWANNSCHWANN “We have seen that all organisms are composed of essentially like parts, namely, of cells.” (1839) RUDOLFRUDOLF VIRCHOWVIRCHOW “Every animal appears as a sum of vital units, each of which bears in itself the complete characteristics of life.” (1858) CELLCELL Rockefeller Nobel Prize Winners in Cell Biology George E. Palade (1974) Christian de Duve (1974) Albert Claude (1974) Günter Blobel (1999) MAMMALIANMAMMALIAN EMBRYOEMBRYO SPERMSPERM ANDAND EGGEGG THETHE CELLCELL The basic unit of life Underpins all reproduction and development Stem cells THETHE GENEGENE Basis of heredity GREGORGREGOR MENDELMENDEL MENDELMENDEL’’SS GARDENGARDEN PEASPEAS PEASPEAS 1919TH CENTURYCENTURY CHROMOSOMESCHROMOSOMES EDOUARDEDOUARD VANVAN BENEDENBENEDEN’’SS NEMATODENEMATODE CHROMOSOMESCHROMOSOMES PNEUMOCOCCUSPNEUMOCOCCUS Avery, MacLeod and McCarty, Rockefeller University (1944) DNADNA MOLECULEMOLECULE CENTRALCENTRAL DOGMADOGMA THETHE GENEGENE Basis of heredity Genotype to phenotype Implications for what we are EVOLUTIONEVOLUTION BYBY NATURALNATURAL SELECTIONSELECTION Life evolves Mechanism of natural selection ERASMUSERASMUS ANDAND CHARLESCHARLES DARWINDARWIN
    [Show full text]
  • George Palade 1912-2008
    George Palade, 1912-2008 Biography George Palade was born in November, 1912 in Jassy, Romania to an academic family. He graduated from the School of Medicine of the The Founding of Cell Biology University of Bucharest in 1940. His doctorial thesis, however, was on the microscopic anatomy of the cetacean delphinus Delphi. He The discipline of Cell Biology arose at Rockefeller University in the late practiced medicine in the second world war, and for a brief time af- 1940s and the 1950s, based on two complimentary techniques: cell frac- terwards before coming to the USA in 1946, where he met Albert tionation, pioneered by Albert Claude, George Palade, and Christian de Claude. Excited by the potential of the electron microscope, he Duve, and biological electron microscopy, pioneered by Keith Porter, joined the Rockefeller Institute for Medical Research, where he did Albert Claude, and George Palade. For the first time, it became possible his seminal work. He left Rockefeller in 1973 to chair the new De- to identify the components of the cell both structurally and biochemi- partment of Cell Biology at Yale, and then in 1990 he moved to the cally, and therefore begin understanding the functioning of cells on a University of California, San Diego as Dean for Scientific Affairs at molecular level. These individuals participated in establishing the Jour- the School of Medicine. He retired in 2001, at age 88. His first wife, nal of Cell Biology, (originally the Journal of Biochemical and Biophysi- Irina Malaxa, died in 1969, and in 1970 he married Marilyn Farquhar, cal Cytology), which later led, in 1960, to the organization of the Ameri- another prominent cell biologist, and his scientific collaborator.
    [Show full text]
  • Evidence for Design in Physics and Biology: from the Origin of the Universe to the Origin of Life
    52 stephen c. meyer Pages 53–111 of Science and Evidence for Design in the Universe. The Proceedings of the Wethersfield Institute. Michael Behe, STEPHEN C. MEYER William A. Dembski, and Stephen C. Meyer (San Francisco: Ignatius Press, 2001. 2000 Homeland Foundation.) EVIDENCE FOR DESIGN IN PHYSICS AND BIOLOGY: FROM THE ORIGIN OF THE UNIVERSE TO THE ORIGIN OF LIFE 1. Introduction In the preceding essay, mathematician and probability theo- rist William Dembski notes that human beings often detect the prior activity of rational agents in the effects they leave behind.¹ Archaeologists assume, for example, that rational agents pro- duced the inscriptions on the Rosetta Stone; insurance fraud investigators detect certain ‘‘cheating patterns’’ that suggest intentional manipulation of circumstances rather than ‘‘natu- ral’’ disasters; and cryptographers distinguish between random signals and those that carry encoded messages. More importantly, Dembski’s work establishes the criteria by which we can recognize the effects of rational agents and distinguish them from the effects of natural causes. In brief, he shows that systems or sequences that are both ‘‘highly com- plex’’ (or very improbable) and ‘‘specified’’ are always produced by intelligent agents rather than by chance and/or physical- chemical laws. Complex sequences exhibit an irregular and improbable arrangement that defies expression by a simple formula or algorithm. A specification, on the other hand, is a match or correspondence between an event or object and an independently given pattern or set of functional requirements. As an illustration of the concepts of complexity and speci- fication, consider the following three sets of symbols: 53 54 stephen c.
    [Show full text]
  • Albert Claude, 1948 the Rockefeller University
    Rockefeller University Digital Commons @ RU Harvey Society Lectures 1950 Albert Claude, 1948 The Rockefeller University Follow this and additional works at: https://digitalcommons.rockefeller.edu/harvey-lectures Recommended Citation The Rockefeller University, "Albert Claude, 1948" (1950). Harvey Society Lectures. 44. https://digitalcommons.rockefeller.edu/harvey-lectures/44 This Book is brought to you for free and open access by Digital Commons @ RU. It has been accepted for inclusion in Harvey Society Lectures by an authorized administrator of Digital Commons @ RU. For more information, please contact [email protected]. STUDIES ON CELLS: MORPHOLOGY, CHEMICAL CONSTITUTION, AND DISTRIBUTION OF BIOCHEMICAL FUNCTIONS* ALBERT CLAUDE Associate Member The Rockefeller Institute for Medical Research N 1827 Giovanni Battista Amici, Italian mathematician and I astronomer from Modena, came to Paris to demonstrate the microscope that he had just perfected. All those interested in natural sciences went to examine the new instrument and, according to Dutrochet, 1 were considerably impressed. A few weeks later Amici was in London, demonstrating his microscope, among others, to Robert Brown, the man who four years later was to discover the cell nucleus. Soon thereafter the leading microscopists of Europe were in possession of one of Amici' s microscopes, or one constructed after his specifications.Amici had finallysucceeded in correcting to a large extent the spherical and chromatic aberrations of microscopic lenses. The morphological details in plant and animal tissues were no longer blurred, hopelessly merging as in the old instruments, but appeared sufficiently well defined to convince microscopists that tissues were composed of an ever repeating unit, which has come to be known as the cell.
    [Show full text]
  • Balcomk41251.Pdf (558.9Kb)
    Copyright by Karen Suzanne Balcom 2005 The Dissertation Committee for Karen Suzanne Balcom Certifies that this is the approved version of the following dissertation: Discovery and Information Use Patterns of Nobel Laureates in Physiology or Medicine Committee: E. Glynn Harmon, Supervisor Julie Hallmark Billie Grace Herring James D. Legler Brooke E. Sheldon Discovery and Information Use Patterns of Nobel Laureates in Physiology or Medicine by Karen Suzanne Balcom, B.A., M.L.S. Dissertation Presented to the Faculty of the Graduate School of The University of Texas at Austin in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy The University of Texas at Austin August, 2005 Dedication I dedicate this dissertation to my first teachers: my father, George Sheldon Balcom, who passed away before this task was begun, and to my mother, Marian Dyer Balcom, who passed away before it was completed. I also dedicate it to my dissertation committee members: Drs. Billie Grace Herring, Brooke Sheldon, Julie Hallmark and to my supervisor, Dr. Glynn Harmon. They were all teachers, mentors, and friends who lifted me up when I was down. Acknowledgements I would first like to thank my committee: Julie Hallmark, Billie Grace Herring, Jim Legler, M.D., Brooke E. Sheldon, and Glynn Harmon for their encouragement, patience and support during the nine years that this investigation was a work in progress. I could not have had a better committee. They are my enduring friends and I hope I prove worthy of the faith they have always showed in me. I am grateful to Dr.
    [Show full text]
  • Albert Claude and the Beginnistgs of Biological Electron Microscopy
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by PubMed Central ALBERT CLAUDE AND THE BEGINNISTGS OF BIOLOGICAL ELECTRON MICROSCOPY GEORGE E. PALADE From The Rockefeller University, New York 100~1 EARLY ELECTRON MICROSCOPES AND THE NEED FOR NEW PREPARATION TECHNIQUES The grcat potential value of electron microscopy for biological research was often strcsscd and quickly understood in the middle 1930s, at the time when thc first laboratory models of transmission electron microscopes were being built by Ruska, yon Borrics (1, 2), and Marton (3, 4). The reasons were clear: the new instruments were expected to have a resolving power 40-50 times higher than the best light microscopes then available. It was also understood from the bcginning that a new technology was needed for preparing biological specimens for electron microscopy, definitely more refined and in some respects quite different from the traditional histological technology then in use for light microscopy. The limited pcnctrafion power of electrons, and the ease with which thcy arc scattered by any atom required that specimens of unusual thinness--for the thinking and experience of thosc times--bc examined in a relatively high vacuum (~ 10-4 torr). The microtomcs then in use for light microscopy could not cut tissue sections thinner than I t~, while the desirable specimen thickness for electron microscopy was estimated at ~-~0.1 ~ or less. In addition, since the specimens were examined in vacuo, they had to withstand the removal of their volatile components, primarily the removal of water, without collapse or deterioration of their structure.
    [Show full text]
  • Vesicular Transport in Cells – from Analysis to Biogenesis
    Powered by Website address: https://www.gesundheitsindustrie- bw.de/en/article/news/vesicular-transport-in-cells-from- analysis-to-biogenesis Vesicular transport in cells – from analysis to biogenesis COPI vesicles, one of the three major types of intracellular transport vesicles, are an excellent example of how the molecular analysis of individual vesicle components can lead to an understanding of the biogenesis and transport mechanisms of membrane vesicles as a whole. The research carried out by Dr. Felix T. Wieland’s team at the University of Heidelberg has made a decisive contribution to such detailed insights. Eukaryotic cells are characterised by complex membrane systems that separate different metabolic compartments from each other at the same time as transporting metabolic products and messenger substances to specific destinations inside the cell and into the extracellular space. The transport is mediated by vesicles that detach from the folded and branched cisternae of intracellular membranes. They either then fuse with intracellular membranes again or with the plasma membrane where the contents of the vesicles, secretory proteins for example, are discharged to the outside of the cell. This process is referred to as exocytosis. The opposite process is known as endocytosis, in which cells take up molecules from the exterior by enveloping them in their cell membrane before releasing them inside the cell. Camillo Golgi (1843-1926). © Universitá degli studi di Pavia The Golgi apparatus, named after the Italian physiologist Camillo Golgi who discovered a method to 1 stain nervous tissue with silver, which led to his discovery in 1898 of the "apparato reticulare interno" in the hippocampal neurons, is integral in modifying and packaging macromolecules for exocytosis or use within the cell (endocytosis).
    [Show full text]
  • Guest Editorial 1 Guest Editorial
    Indian JJ PhysiolPhysiol PharmacolPharmacol 2012; 2012; 56(1) 56(1) : 1–6 Guest Editorial 1 Guest Editorial IMMUNOLOGY AND NOBEL PRIZE : A LOVE STORY Several breakthroughs revealing the way in which our bodies protect us against microscopic threats of almost any description have been duly acknowledged by the Nobel Prizes in Physiology or Medicine. Interestingly, Nobel Prizes in Physiology or Medicine including the latest one, for the year 2011, has been awarded for twelve times to the field of Immunology. The story began in 1901 with the very first Nobel Prize in Physiology or Medicine - it was awarded to Emil Von Behring for his pioneering work which resulted in the discovery of antitoxins, later termed as antibodies. Working with Shibasaburo Kitasato, Von Behring found that when animals were injected with tiny doses of weakened forms of tetanus or diphtheria bacteria, their blood extracts contained chemicals released in response, which rendered the pathogens’ toxins harmless. Naming these chemical agents ‘antitoxins’, Von Behring and Erich Wernicke showed that transferring antitoxin-containing blood serum into animals infected with the fully virulent versions of diphtheria bacteria cured the recipients of any symptoms, and prevented death. This was found to be true for humans also; and thus Von Behring’s method of treatment – passive serum therapy – became an essential remedy for diphtheria, saving many thousands of lives every year. Shortly after this, the very first explanation about the mechanisms of immune system’s functioning was proposed which paved way for extensive research in immunology till today. Paul Ehrlich had hit upon the key concept of how antibodies seek and neutralize the toxic actions of bacteria, while Ilya Mechnikov had discovered that certain body cells could destroy pathogens by simply engulfing or “eating” them.
    [Show full text]
  • A Tribute to George E. Palade
    A tribute to George E. Palade James D. Jamieson J Clin Invest. 2008;118(11):3517-3518. https://doi.org/10.1172/JCI37749. Obituary George E. Palade (1912–2008) received his MD from the School of Medicine of the University of Bucharest, Romania. He was a member of the faculty of that school until 1945, when he came to the United States for postdoctoral studies. Palade joined Albert Claude at the Rockefeller Institute for Medical Research in 1946 and was appointed assistant professor there in 1948. He progressed to full professor and was head of the Laboratory of Cell Biology until 1973, when he moved to Yale University as professor to establish the Section of Cell Biology. He wrote that his move to Yale was driven by “. 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” (1). Palade was chair of the Section of Cell Biology from 1975 to 1983, when, upon his retirement as chair, it became the Department of Cell Biology. That same year he was named Senior Research Scientist, Professor Emeritus of Cell Biology, and Special Advisor to the Dean. In 1990, Palade moved to the University of California, San Diego. Once again, he welcomed a new challenge and began an entirely new career as Professor of Medicine in Residence and Dean for Scientific Affairs in the […] Find the latest version: https://jci.me/37749/pdf Obituary A tribute to George E. Palade George E.
    [Show full text]
  • Scientific Background: Discoveries of Mechanisms for Autophagy
    Scientific Background Discoveries of Mechanisms for Autophagy The 2016 Nobel Prize in Physiology or Medicine is a previously unknown membrane structure that de awarded to Yoshinori Ohsumi for his discoveries of Duve named the lysosome1,2. Comparative mechanisms for autophagy. Macroautophagy electron microscopy of purified lysosome-rich liver (“self-eating”, hereafter referred to as autophagy) is fractions and sectioned liver identified the an evolutionarily conserved process whereby the lysosome as a distinct cellular organelle3. Christian eukaryotic cell can recycle part of its own content de Duve and Albert Claude, together with George by sequestering a portion of the cytoplasm in a Palade, were awarded the 1974 Nobel Prize in double-membrane vesicle that is delivered to the Physiology or Medicine for their discoveries lysosome for digestion. Unlike other cellular concerning the structure and functional degradation machineries, autophagy removes organization of the cell. long-lived proteins, large macro-molecular complexes and organelles that have become Soon after the discovery of the lysosome, obsolete or damaged. Autophagy mediates the researchers found that portions of the cytoplasm digestion and recycling of non-essential parts of the are sequestered into membranous structures cell during starvation and participates in a variety during normal kidney development in the mouse4. of physiological processes where cellular Similar structures containing a small amount of components must be removed to leave space for cytoplasm and mitochondria were observed in the new ones. In addition, autophagy is a key cellular proximal tubule cells of rat kidney during process capable of clearing invading hydronephrosis5. The vacuoles were found to co- microorganisms and toxic protein aggregates, and localize with acid-phosphatase-containing therefore plays an important role during infection, granules during the early stages of degeneration in ageing and in the pathogenesis of many human and the structures were shown to increase as diseases.
    [Show full text]