DOCSLIB.ORG

Leonard Herzenberg (1931–2013) Immunologist Who Pioneered Cell-Sorting Technology

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Leonard Herzenberg (1931–2013) Immunologist Who Pioneered Cell-Sorting Technology COMMENT OBITUARY Leonard Herzenberg (1931–2013) Immunologist who pioneered cell-sorting technology. eonard Herzenberg, together with his biochemist César Milstein on his technology wife and scientific partner of more to fuse cells. They created cell lines that pro- than 60 years, Leonore, transformed duce made-to-order antibodies which attach Limmunology. His accomplishments con- to specific markers on cell surfaces. tinue to influence every aspect of modern Len recognized the power of this tech- biological science. nology to identify specific proteins and cell Were it not for Herzenberg, researchers populations. Lee coined the term ‘hybridoma’ might still be waiting for fast, precise ways for a class of workhorse lab cells, a combina- SCHOOL OF MEDICINE STANFORD to count and sort cells. That task, now rou- tion of an antibody-producing white blood tine, is essential for working out how cancers cell and an immortal tumour cell. and tissues grow, and for diagnosing certain Although Herzenberg’s patents are among diseases. Herzenberg also developed tech- Stanford’s highest earning, he believed that nologies to create monoclonal antibodies — any scientific advance belonged to the lab-produced versions of the proteins used people who had funded it; that is, to the by the immune system to recognize danger- public, whose taxes supported his grants. ous cells and toxins. These are now deployed He asked co-inventors of flow cytometry in laboratories for innumerable assays, and to assign patent royalties back to the lab. He in humans for certain cancers, infections and freely shared resources that his laboratory inflammatory diseases. developed, providing researchers from other Herzenberg, who died on 27 October labs with reagents, cell lines, data and infor- aged 81, was born in New York City. After mation, sometimes well before publication. graduating in 1952 from Brooklyn College This collaborative philosophy was appreci- in New York, he began doctoral studies ated by scientists worldwide. It also helped in genetics at the California Institute of to accomplish his primary goal: more-rapid Technology in Pasadena, joining a depart- advances. ment that included seven future Nobel Throughout his career, Herzenberg was laureates. Among this auspicious group, In the 1960s, after moving to California actively involved in sociopolitical causes. Herzenberg blossomed scientifically and, to work at Stanford University, Herzenberg His early exposure to the dangers of the along with Leonore, whom he had met at recognized the need for an automated, high- anti-intellectualism and misinformation Brooklyn College, he also became politi- throughput method to enumerate and sep- of McCarthyism seeded a lifelong commit- cally active. Len and Lee, as they were arate rare cells in a population of millions. ment to bringing rational thought to public known, worked with a chemist down the Such technology could be used, for example, discourse. He railed against proponents of hall — Linus Pauling, who himself would to explore whether individual immune cells eugenics and nuclear proliferation, and, in go on to win two Nobel prizes — to start a made one or several kinds of antibodies, or later years, against those who stigmatized local chapter of the Federation of American to identify those producing antibodies capa- people with HIV. Scientists that worked to combat the insidi- ble of killing cancer cells. He also supported efforts to promote ous efforts of McCarthyism in the 1950s, Herzenberg formed a team of engineers career opportunities and equality for among other goals. and biologists to take a machine that sorted women and minorities in science. The Her- After Len received his PhD, the Herzen- particles by size and enhance it with tech- zenbergs established programmes to bring bergs moved to Paris, where Len did a fel- niques to detect fluorescence and manipu- disadvantaged young people in California’s lowship at the Pasteur Institute with biologist late droplets. The result was modern flow San Francisco Bay Area to Stanford to learn and Nobel laureate Jacques Monod. Discus- cytometry — a way to count and separate about medical research. Lee continues this sions at lunch revolved alternately around viable cells in a stream of fluid lit by lasers tradition of balancing outreach with scien- bacterial genetics and the French Resist- that reveal fluorescent markers on the cells. tific research. ance. While abroad, Herzenberg was drafted Fluorescence-activated cell sorting (known Although Len is considered the father into the US peacetime army. He arranged as FACS) is now widely used in labs and hos- of modern flow cytometry, his contribu- to serve in the Public Health Service and pitals. For instance, FACS can isolate fetal tions extend far beyond that. He was a great moved to Bethesda, Maryland, to join the cells from maternal blood, which allows scientist, a great collaborator and a great lab of pathologist Harry Eagle at the US clinicians to perform genetic testing using a mentor. ■ National Institutes of Health. Here, Herzen- minimally invasive procedure. Remarkably, berg “carried a pipette rather than a gun” for the fundamental aspects of FACS have not Mario Roederer is senior investigator in his country. He helped to define the minimal changed in the more than 40 years since its the ImmunoTechnology Section, Vaccine components of the nutrient broth necessary invention. Research Center, US National Institute of to clone cells. More than a decade later, this Another ubiquitous technology also owes Allergy and Infectious Diseases, Bethesda, enabled him to produce antibodies in cell its existence to the Herzenbergs. In 1976, Maryland. He was in the Herzenbergs’ culture, a technology that generates billions on a sabbatical at the University of Cam- laboratory from 1988 to 1999. of dollars’ worth of drugs and lab reagents. bridge, UK, the Herzenbergs worked with e-mail: [email protected] 34 | NATURE | VOL 504 | 5 DECEMBER 2013 © 2013 Macmillan Publishers Limited. All rights reserved.
Load more

Recommended publications
  • 2012 Single Cell Analysis Workshop
    2012 Single Cell Analysis Workshop Where: Hyatt Regency, Bethesda MD When: April 17-18, 2012 Co-chairs: Dr. Gary Nolan (Stanford University) and Dr. Nancy Allbritton (University of North Carolina) The NIH Common Fund held a Single Cell Analysis meeting on April 17-18, 2012 in Bethesda, MD. The objective was to provide a forum to bring together a multidisciplinary group of investigators and federal staff to discuss the latest technological advances and transformative discoveries in the area of single cell analysis. The focus was on approaches that further our understanding of cell heterogeneity or variation, including identifying unique cell types and cell “states”. The goal was to share knowledge and accelerate the dissemination of technological advances within the relevant research community. The format incorporated short talks, poster presentations, and panel discussions providing the group with opportunities to review recent progress and consider the major challenges facing the field over the next decade. There were over 90 registered participants from academia as well as the public and private sectors with 20 attendees presenting posters during two day meeting. Four presentation/discussion sessions were held. A general description and summary of each follows. Session 1—Profiling Individual Cell State: Genomics Roger Lasken, Craig Venter Institute Barbara Wold, California Institute of Technology Robert Singer, Albert Einstein College of Medicine Paul Soloway, Cornell University Junhyong Kim, University of Pennsylvania Presenters discussed sequencing whole genomes at the level of a single cell or single nuclei; measuring and visualizing RNA expression and localization including technical challenges associated with multiplexed analyses; advances in single cell epigenomic analysis; and bioinformatics and computational questions using genomic/transcriptomic data from single cell experiments.
    [Show full text]
  • CURRICULUM VITAE GARRY P. NOLAN, Ph.D
    CURRICULUM VITAE GARRY P. NOLAN, Ph.D. __________________________________________________________________________________________ EDUCATION UNDERGRADUATE SCHOOL 1979-1983 Cornell University B.S., Biology, specialization in Genetics Research: Rhizobium/Legume Microbial Genetics, Advisor: Professor Aladar Szalay __________________________________________________________________________________________ GRADUATE SCHOOL 1983-1989 Scientific Advisor: Professor Leonard Herzenberg Ph.D., Department of Genetics, Stanford University . Research: Immunogenetics, Individual Cell Gene Expression . Thesis: Individual cell gene regulation studies and in situ detection of transcriptionally-active chromatin using fluorescence-activated cell sorting with a viable cell fluorogenic assay 1989-1990 Continuing Post-Graduate Research: Epigenetics of Mammalian Gene Expression; Whole Animal Cell Sorting. __________________________________________________________________________________________ POSTDOCTORAL WORK 1990-1993 Scientific Advisor: Professor David Baltimore Postdoctoral Fellow . NIH Fellowship Program . Leukemia Society Special Fellow Research conducted at: . Whitehead Institute for Biomedical Research (MIT) . Rockefeller University Research: . The NF-κB/IκB proteins (cloning and characterization of p65/RelA). Development of 293T based retroviral packaging and delivery systems __________________________________________________________________________________________ FACULTY POSITIONS 2011-present Rachford and Carlota A. Harris Professor Department of
    [Show full text]
  • 1 Cytometry and Cytometers: Development and Growth
    1 1 Cytometry and Cytometers: Development and Growth Howard M. Shapiro Overview It took almost 200 years of microscopy, from the mid-1600s until the mid-1800s, before objective data could be derived from specimens under the microscope by photography. The subsequent development of both image and flow cytometry for use by biologists followed the development of photometry, spectrometry, and flu- orometry by physicists and chemists. Early cytometers measured cellular charac- teristics, such as nucleic acid content at the whole cell level; since few reagents were available that could specifically identify different types of cells, higher reso- lution imaging systems were developed for this task, but were too slow to be prac- tical for many applications. The development of flow cytometry and cell sorting facilitated the development of more specific reagents, such as monoclonal anti- bodies and nucleic acid probes, which now allow cells to be precisely identified and characterized using simpler, low-resolution imaging systems. Although the most complex cytometers remain expensive, these newer instruments may bring the benefits of cytometry to a much wider community of users, including bota- nists in the field. 1.1 Origins If the microscopic structures in cork to which Robert Hooke gave the name ‘‘cells’’ in the mid-17th century may be compared to the surviving stone walls of an ancient city, to what are we to compare the vistas available to 21st-century microscopists, who can follow the movements of individual molecules through living cells? Between the time Hooke named them and the time that Schleiden, Schwann, and Virchow established cells as fundamental entities in plant and animal struc- ture, function, and pathology, almost two centuries had elapsed.
    [Show full text]
  • A Century of Geneticists Mutation to Medicine a Century of Geneticists Mutation to Medicine
    A Century of Geneticists Mutation to Medicine http://taylorandfrancis.com A Century of Geneticists Mutation to Medicine Krishna Dronamraju CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 © 2019 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works Printed on acid-free paper International Standard Book Number-13: 978-1-4987-4866-7 (Paperback) International Standard Book Number-13: 978-1-138-35313-8 (Hardback) This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint. Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, trans- mitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright .com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc.
    [Show full text]
  • Leonard a Herzenberg 1931–2013
    OBITUARY Leonard A Herzenberg 1931–2013 Garry P Nolan On 27 October 2013, just a week before his 82nd birthday, Leonard sorting and the ‘modern age’ of immunology arrived, the principles (Len) A. Herzenberg passed away from complications due to a stroke. of which are still relevant today. It is to Len’s everlasting credit that Joining him during his final hours was Leonore (Lee) A. Herzenberg, the absolute rule of his laboratory was to share any reagents devel- his wife and scientific partner for nearly his entire research career. oped under a ‘no questions asked, no limitations imposed’ policy— He is survived by Lee and his children Jana, Berri, John and Rick. He open-access science in the making. leaves a research community indebted to his service to the public’s The data-management solutions taking root in the Herzenberg benefit, and he leaves hundreds of thousands of patients, and more, laboratory under the leadership of Lee Herzenberg formed a forerun- who have benefitted from his brilliant contributions to immunology ner to the bioinformatics revolution taking place today. As ‘Len and and translational medicine. Lee’, they led an extraordinarily diverse and intermingled team that Who today can imagine modern immunology without cell sorting not only built the instruments that tabulated the expression and cor- or fluorescence-labeled antibodies? How would simple blood profil- relations of critical proteins from thousands to millions of cells per ing be done? How could the extraordinary intricacies of lineages and experiment but also spent endless hours pondering immunological sublineages of the immune system be delineated, or the diversity of mechanisms or arguing about how to develop intuitive representa- cell types in a tumor be understood? How could the discoveries that tions of the deeply phenotypic data to provide a vision on how best HIV-1 specifically attacks CD4+ T cells and that the onset of AIDS to ask the next questions.
    [Show full text]
  • New Generation Cell Sorters: BD Facsaria II and BD Influx Systems
    HotLinesBD Biosciences | Volume 13, No 1 New Generation Cell Sorters: Dr Didier Ebo–Basophil Activation in Allergy BD FACSAria II and BD Influx Systems Assessment–Go with the Flow Fluorescent Protein Organelle Markers and their Utility in Multiplexed Live and Fixed Cell Assays Analyzing Neural Differentiation of Human Embryonic Stem Cells by Bioimaging and Flow Cytometry Interview with Timothy Bushnell, PhD, Director, CPBR Flow Cytometry Laboratory p53 Acetylation: A Call to Action Ficoll-Paque™ PLUS is a trademark of GE Healthcare BD flow cytometers are Class I (1) laser products. Companies. Alexa Fluor® and MitoTracker® are For Research Use Only. Not for use in diagnostic or registered trademarks of Molecular Probes, Inc. therapeutic procedures. Not for resale. All applications are either tested in-house or reported in the literature. Accutase™ is a trademark of Millipore. See Technical Data Sheets for details. © 2008 Becton, Dickinson and Company. All rights reserved. Cy™ is a trademark of Amersham Biosciences Corp. Cy dyes are subject to proprietary rights of Amersham No part of this publication may be reproduced, Biosciences Corp and Carnegie Mellon University and are transmitted, transcribed, stored in retrieval systems, or made and sold under license from Amersham Biosciences translated into any language or computer language, Corp only for research and in vitro diagnostic use. in any form or by any means: electronic, mechanical, Any other use requires a commercial sublicense from magnetic, optical, chemical, manual, or otherwise, Amersham Biosciences Corp, 800 Centennial Avenue, without prior written permission from BD Biosciences. Piscataway, NJ 08855-1327, USA. Purchase does not include or carry any right to resell or transfer this product either as a stand-alone product The Alexa Fluor®, Pacific Blue™, and Cascade Blue® or as a component of another product.
    [Show full text]
  • A Conversation with Leonard and Leonore Herzenberg
    PH76-FrontMatter ARI 22 January 2014 18:37 Annu. Rev. Physiol. 2014.76:1-20. Downloaded from www.annualreviews.org Access provided by Stanford University - Main Campus Robert Crown Law Library on 06/29/16. For personal use only. PH76CH01-Roederer ARI 11 January 2014 11:18 A Conversation with Leonard and Leonore Herzenberg Leonard A. Herzenberg,1,∗ Leonore A. Herzenberg,1 and Mario Roederer2 1Department of Genetics, Stanford University, Stanford, California 94305 2ImmunoTechnology Section, Vaccine Research Center, National Institutes of Health, Baltimore, Maryland 20892; email: [email protected] Annu. Rev. Physiol. 2014. 76:1–20 Keywords First published online as a Review in Advance on flow cytometry, hybridomas, immunology, technology August 19, 2013 Annu. Rev. Physiol. 2014.76:1-20. Downloaded from www.annualreviews.org The Annual Review of Physiology is online at Abstract http://physiol.annualreviews.org Leonard and Leonore Herzenberg have left an indelible mark on the fields This article’s doi: of immunology and cell biology, both in research and clinical aspects. They 10.1146/annurev-physiol-021113-170355 are perhaps best known for developing the technologies of fluorescence flow Copyright c 2014 by Annual Reviews. cytometry and hybridomas. Over six decades, they made a number of impor- All rights reserved tant and fundamental discoveries in lymphocyte biology by applying these Access provided by Stanford University - Main Campus Robert Crown Law Library on 06/29/16. For personal use only. ∗ November 5, 1931–October 27, 2013 technologies. During this era, they immersed themselves in the sociopoliti- cal environment, interjecting scientific rationale into public discourse about McCarthyism, nuclear fallout, war, genetics, and other politically charged topics.
    [Show full text]
  • Myths About Stanford's Interactions with Industry Timothy Lenoir
    Myths about Stanford’s Interactions with Industry Timothy Lenoir Department of History Stanford University Draft: September 6, 2004 Stanford is typically featured as a paradigm example among universities generating innovations that lead to new technology-based firms; and indeed, Stanford entrepreneurial activity is generally regarded as virtually synonymous with the birth of Silicon Valley. This is the stuff of legend, but it is based in fact: In a study conducted in 2000 Tom Byers and colleagues argued that Stanford alumni and faculty account for more than 1800 technology based firms in the Silicon Valley responsible for 37 percent of all high-tech employment in the region1; and in his contribution to the Silicon Valley Edge, Jim Gibbons, himself a Silicon Valley legend, argued that Stanford technology startups, including Hewlett-Packard, accounted for 60 percent of Silicon Valley revenues in 1988 and 1996 if Hewlett-Packard is included in the accounting and slightly over 50 percent if HP is left out of the mix.2 But such accounts can be misleading. While it is undoubtedly correct that Stanford has been a significant factor in the formation of Silicon Valley undue emphasis on Stanford’s contributions can contribute to the myth that Stanford’s interaction with industry is a one way relationship. A second, equally distorted description of Stanford’s relation to industry is the view that in the wake of a continuous decline in federal funding for academic research over the past decade Stanford has somehow become the captive of industry funding, and that in the aftermath of Bayh-Dole and the gold rush on biotechnology patents, Stanford has become a “kept university” seeking to turn its intellectual property into a cash cow to keep up in the research game.
    [Show full text]
  • Directed Evolution: a Historical Exploration Into an Evolutionary Experimental System of Nanobiotechnology, 1965–2006
    Minerva (2008) 46:463–484 DOI 10.1007/s11024-008-9108-9 Directed Evolution: A Historical Exploration into an Evolutionary Experimental System of Nanobiotechnology, 1965–2006 Eun-Sung Kim Published online: 27 November 2008 Ó Springer Science+Business Media B.V. 2008 Abstract This study explores the history of nanotechnology from the perspective of protein engineering, which differs from the history of nanotechnology that has arisen from mechanical and materials engineering; it also demonstrates points of convergence between the two. Focusing on directed evolution—an experimental system of molecular biomimetics that mimics nature as an inspiration for material design—this study follows the emergence of an evolutionary experimental system from the 1960s to the present, by detailing the material culture, practices, and techniques involved. Directed evolution, as an aspect of nanobiotechnology, is also distinct from the dominant biotechnologies of the 20th century. The experimental systems of directed evolution produce new ways of thinking about molecular diversity that could affect concepts concerning both biology and life. Keywords Directed evolution Á RNA world Á Scanning probe microscopy Á Molecular biomimetics Á Nanotechnology Á Molecular diversity Introduction A hallmark of nanotechnology (NT) is that it has been difficult to define as a distinct field, due to the multiple techniques, diverse materials, and histories involved. NT has generally been defined as the control of materials on a scale of 1–100 nm.1 Beyond this simple definition, the term is ambiguous vis-a`-vis material identity. However, the history of NT has been written exclusively with regard to inorganic 1 National Nanotechnology Initiative. What is Nanotechnology? http://www.nano.gov/html/facts/what IsNano.html.
    [Show full text]
  • Pyrene at Nanomolar Concentrations by Intact Murine Hepatoma Cells1
    [CANCER RESEARCH 42, 4473-4478, November 1982] 0008-5472/82/0042-OOOOS02.00 Efficient Metabolism of Benzo(a)pyrene at Nanomolar Concentrations by Intact Murine Hepatoma Cells1 Arthur G. Miller2 and James P. Whitlock, Jr.3 Department of Pharmacology, Stanford University School of Medicine, Stanford, California 94305 ABSTRACT We have shown previously that the disappearance of BP fluo rescence is due to metabolism of BP (24). Using this assay, we We have studied the metabolism of benzo(a)pyrene (BP) by found rapid metabolism of BP at nM levels, similar to those in intact mouse hepatoma cells, at nM concentrations of the the environment. These results seemed incompatible with pre carcinogen, using an assay in which we directly measure the vious studies of BP metabolism using the standard AHH assay, rate of BP fluorescence disappearance. The rate of BP metab in which the apparent Kmfor BP metabolism was found to be in olism is half-maximal, at limiting cell dilution, when the concen the ¡IMrange (20, 27, 38). In fact, we were unable to detect tration of BP is about 4 nM. This apparent Kmfor BP metabolism metabolism, using the AHH assay, at a BP concentration at is much lower than those reported previously for several rea which the rate of metabolism was half-maximal, as measured sons, (a) Partitioning of BP into cells markedly influences by the BP disappearance assay. Therefore, we performed kinetic measurements, and we account for these effects, (b) experiments to further characterize BP metabolism at low con Enzyme inducers can competitively inhibit BP metabolism and centrations and to determine the relation between the BP thus may introduce artifacts into kinetic measurements, (c) disappearance assay and the AHH assay.
    [Show full text]
  • December 2012
    Vol. 11 No. 12 December 2012 American Society for Biochemistry and Molecular Biology contents DECEMBER 2012 On the cover: In this issue, science writer news Rajendrani Mukhopadhyay explores a controversy over 3 President’s Message a dietary recommendation The field of (Nobel) dreams for omega-6 fatty acids that shows no signs of resolving 5 News from the Hill itself. 14 Congress’ unfinished business 6 Member Update 9 Protecting biomedical inventions Ben Wiehe, manager through patents of the Science Festival Alliance, reflects on the diverse activities features at the 2012 Bay Area Science Festival and 11 Meet Peter Cresswell offers advice for those new JBC associate editor considering putting a 14 An essential debate festival together. 26 departments 20 Journal News 20 MCP: Tiny mitochondrial intermembrane space’s proteome 21 JLR: How high cholesterol levels come in The results of the ASBMB 2012 handy during protozoan infection graduation survey are in! 30 21 JBC: Insights into a new therapy for a rare form of cystic brosis 22 JBC: JBC thematic minireview series on HIV and the host 23 JBC: The road well traveled together: a joint “Reections” by Leonore and Leonard Herzenberg Not sure how to go about 26 Outreach obtaining a patent? Gaby L. Zombies, beer and family-friendly, Longsworth and Chenghua sun-filled afternoons Luo of the law firm of Sterne, Kessler, Goldstein 30 Education & Fox offer a primer. 9 The ASBMB 2012 graduation survey 32 Open Channels p chns Which cellular organelle would get your vote? Brad Graba, a biology teacher in Illinois, took advantage of the election-season hype and engaged his students on campus and on Twitter in a campaign that pitted organelles against organelles.
    [Show full text]
  • The History of the Cell Sorter Videohistory Collection, 1991
    The History of the Cell Sorter Videohistory Collection, 1991 Finding aid prepared by Smithsonian Institution Archives Smithsonian Institution Archives Washington, D.C. Contact us at [email protected] Table of Contents Collection Overview ........................................................................................................ 1 Administrative Information .............................................................................................. 1 Historical Note.................................................................................................................. 1 Introduction....................................................................................................................... 4 Descriptive Entry.............................................................................................................. 4 Names and Subjects ...................................................................................................... 5 Container Listing ............................................................................................................. 7 The History of the Cell Sorter Videohistory Collection https://siarchives.si.edu/collections/siris_arc_217722 Collection Overview Repository: Smithsonian Institution Archives, Washington, D.C., [email protected] Title: The History of the Cell Sorter Videohistory Collection Identifier: Record Unit 9554 Date: 1991 Extent: 7 videotapes (Reference copies). 12 digital .wmv files and .rm files (Reference copies). Creator:: Language: English Administrative
    [Show full text]