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To Catch a Virus
Trace the evolution of diagnostic virology from yellow fever to COVID-19
Join expert storytellers John Booss, Marilyn J. August, and Marie Louise Landry in a journey through the history of viral epidemics and the detective work of those determined to identify the culprits and treat the infected.
From the identification of the first virus in the late 1800s to the molecular techniques that enabled the rapid recognition of and vaccine development for the SARS-CoV-2 virus, viral diagnostic methods have progressed over the past century to become a formidable tool in human health care. This collection of gripping historical narratives covers a range of fascinating outbreaks and public health challenges, from yellow fever and smallpox to AIDS and COVID-19. This new edition chronicles the ongoing story of the COVID-19 pandemic, highlighting the people, the pathogen, and the progress in the diagnostic laboratory and clinical settings that has touched every aspect of global health.
The many photographs and rich biographical sketches of key figures, diagrams of diagnostic procedures, micrographs of virus-infected cells, timelines, and a new glossary of key terms make To Catch a Virus compelling reading. This book serves as an excellent resource for courses in virology, immunology, microbiology, and public health.
As the world struggles with the ongoing pandemic of SARS-CoV-2/COVID-19, To Catch a Virus is an insightful and superbly told story that chronicles the incredible metamorphosis of diagnostic virology and the technological advances that now make it possible to quickly and accurately detect and monitor the many disease-causing viruses that plague humankind. A stimulating, informative, and absorbing read that is highly recommended.
—Richard L. Hodinka, PhD, Professor Emeritus, Perelman School of Medicine at the University of Pennsylvania; former Director, Clinical Virology Laboratory, Children’s Hospital of Philadelphia
To Catch a Virus provides a beautifully written and compelling story of scientific discovery. It carefully traces the understanding of viral diseases from the turn of the twentieth century to the present. For general readers the authors provide timely and expert guidance to the extraordinary advances in diagnosis, surveillance, and therapeutics that constitute the silver lining in the otherwise somber years of COVID-19. For anyone wishing to understand the challenges confronting virologists and their accomplishments to date, this work is the place to start.
—Frank M. Snowden, PhD, Andrew Downey Orrick Professor Emeritus of History, Yale University; former Chair, Program in History of Science and History of Medicine, Yale University
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Veröffentlichungsjahr: 2022
Cover
Title Page
Copyright
List of Illustrations
Acknowledgments
Foreword
Preface
About the Authors
1 Fear or Terror on Every Countenance
INTRODUCTION
GERM THEORY
BIRTH OF VIROLOGY, “FILTERABLE VIRUSES”
WALTER REED AND THE YELLOW FEVER COMMISSION
REFERENCES
2 Of Mice and Men
INTRODUCTION
RABIES: DOGS AND RABBITS
POLIO: MONKEYS
ARTHROPOD‐BORNE DISEASES, YELLOW FEVER, AND EPIDEMIC ENCEPHALITIDES: MONKEYS AND MICE
INFLUENZA: FERRETS
EMBRYONATED EGGS
REFERENCES
3 Filling the Churchyard with Corpses
INTRODUCTION
PROTECTION: THE CASE OF SMALLPOX
START OF THE SCIENCE OF IMMUNOLOGY: PHAGOCYTOSIS AND HUMORAL IMMUNITY
ANTIVIRAL NEUTRALIZATION AND PROTECTION
STANDARDIZATION OF REAGENTS FOR THE FIRST DIAGNOSTIC LABORATORIES
REFERENCES
4 What Can Be Seen
INTRODUCTION
RUDOLF VIRCHOW AND CELLULAR PATHOLOGY
ADVANCES IN LIGHT MICROSCOPY
ADVANCES IN TISSUE PREPARATION
RABIES—NEGRI BODIES
SMALLPOX—GUARNIERI BODIES AND ELEMENTARY BODIES
VARICELLA—INTRANUCLEAR INCLUSIONS AND MULTINUCLEATED CELLS
CYTOMEGALIC INCLUSION DISEASE OF THE NEWBORN
THE BEGINNINGS OF ELECTRON MICROSCOPY AND VIROLOGICAL STUDIES
REFERENCES
5 The Turning Point
INTRODUCTION
THE BEGINNINGS OF TISSUE CULTURE
EARLY APPLICATIONS OF TISSUE CULTURE TO VIRAL GROWTH
FDR … “… BY FRIDAY EVENING HE LOST THE ABILITY TO WALK OR MOVE HIS LEGS …”
THE GROWTH OF POLIOVIRUS
IN VITRO
: “IT WAS ALMOST AN AFTERTHOUGHT”
THE FIRST VIRAL DIAGNOSTIC LABORATORY
THE FIRST DIAGNOSTIC VIROLOGY LABORATORY IN THE U.S. CIVILIAN SECTOR
REFERENCES
6 A Torrent of Viral Isolates
INTRODUCTION
DIAGNOSTIC VIROLOGY IN UNIVERSITY HOSPITAL LABORATORIES
THE BEGINNINGS OF DIAGNOSTIC VIROLOGY AT THE CDC
THE LID AT THE NIH
REFINEMENTS IN CELL CULTURE METHODS AND DIFFERENTIAL SUSCEPTIBILITY FOR VIRAL DIAGNOSIS
PROFUSION OF ISOLATES, TAXONOMY, AND THE QUESTION OF DISEASE CAUSATION
REFERENCES
7 Imaging Viruses and Tagging Their Antigens
INTRODUCTION
REFINEMENTS OF EM
TIMELINESS OF DIAGNOSIS: THE DEVELOPMENT OF FA
REFERENCES
8 Immunological Memory
INTRODUCTION
HISTORICAL ORIGINS OF HEPATITIS IN CATARRHAL JAUNDICE AND HOMOLOGOUS SERUM JAUNDICE
BARUCH BLUMBERG, AUSTRALIA ANTIGEN, AND POSTTRANSFUSION HEPATITIS
ROSALYN YALOW AND SOLOMON BERSON: DEVELOPMENT OF RIA
EIA AND ELISA
WESTERN BLOTS
IMMUNOGLOBULIN CLASSES
MONOCLONAL ANTIBODIES
REFERENCES
9 To the Barricades
INTRODUCTION
INHERITANCE, DNA, AND THE DOUBLE HELIX
HIV AND THE AIDS EPIDEMIC
EARLY DIAGNOSTIC APPLICATIONS OF MOLECULAR NUCLEIC ACID TECHNIQUES
PCR AND OTHER NUCLEIC ACID AMPLIFICATION TESTS
FUTURE DIRECTIONS FOR MOLECULAR DIAGNOSTICS AND VIRAL PATHOGEN DISCOVERY…THE NEXT CHAPTER
REFERENCES
10 The World Changed
INTRODUCTION
HISTORY OF THE PANDEMIC
THE VIRUS AND ITS VARIANTS
VACCINES: THE NEW “ARMS RACE”
DIAGNOSTIC TESTS
CLINICAL DILEMMAS
THERAPIES
CULTURAL IMPACT OF THE PANDEMIC
THE FUTURE
REFERENCES
Appendix: Chapter timelines
Glossary
Index
End User License Agreement
Chapter 1
TABLE 1 Milestones in the golden age of bacteriology
a
Chapter 10
TABLE 1 Examples of variants of concern (VOCs) of global significance
a
(46)
Chapter 1
FIGURE 1 Specter of death waiting over Panama (U. J. Keppler, 1904). Yellow fe...
FIGURE 2 van Leeuwenhoek exhibiting his microscopes for Catherine of England (...
FIGURE 3 Robert Koch, about 1908. Koch developed the methodology that allowed ...
FIGURE 4 Martinus Beijerinck in his laboratory, May 1921. Beijerinck, like Iva...
FIGURE 5 Henry Rose Carter, 1909. As a member of the Marine Hospital Service, ...
FIGURE 6 George Miller Sternberg. Known as America's first bacteriologist, he ...
FIGURE 7 The Yellow Fever Commission consisted of (upper left) Walter Reed, wh...
Chapter 2
FIGURE 1 Mad Dog. The fear of rabid dogs has been portrayed throughout history...
FIGURE 2 Louis Pasteur. Pasteur was one of the principal founders of germ theo...
FIGURE 3 Rabies prevention. The recognition that the Pasteurian treatment coul...
FIGURE 4 Karl Landsteiner. Landsteiner was awarded the Nobel Prize in 1930 for...
FIGURE 5 “Coughs and Sneezes Spread Diseases,” a slogan and poster campaign th...
FIGURE 6 L'influenza à Paris. This cover is from a Parisian weekly in 1890 dur...
Chapter 3
FIGURE 1 Lady Mary Wortley Montagu. Lady Montagu, an aristocrat of considerabl...
FIGURE 2 Edward Jenner. Jenner was an English physician with an intense intere...
FIGURE 3 Triomphe de la Petite Vérole (Triumph of Smallpox). Vaccination was f...
FIGURE 4 Elie Metchnikoff. Metchnikoff's studies of phagocytosis initiated the...
FIGURE 5 Jules Bordet. With his brother‐in‐law, Octave Gengou, Bordet demonstr...
FIGURE 6 Complement fixation. In stage 1, complement, antigen, and antibodies ...
FIGURE 7 Neutralization test in tissue culture. In the first stage, antibodies...
FIGURE 8 Hemadsorption. Tissue culture cells infected with certain viruses pro...
Chapter 4
FIGURE 1 Rudolf Virchow caricature. Virchow's Cellular Pathology revolutio...
FIGURE 2 Advertisement for achromatic microscopes, 1859. Optical aberrations, ...
FIGURE 3 Poster of a rabid dog. Perhaps the oldest recognized and most feared ...
FIGURE 4 Negri bodies in brain. The observation of intracytoplasmic inclusion ...
FIGURE 5 Varicella‐zoster virus inclusions in a monolayer of human diploid fib...
FIGURE 6 Tzanck smear. Tzanck smears, performed at the bedside, offer a rapid ...
FIGURE 7 Cytomegalovirus inclusions. Cytomegalovirus inclusions, originally th...
FIGURE 8 Bodo von Borries (left) and Ernst Ruska in the early 1930s on vacatio...
FIGURE 9 Max Knoll (left) and Ernst Ruska with an early transmission electron ...
FIGURE 10 Helmut Ruska, circa 1930. As the younger brother of Ernst Ruska and ...
FIGURE 11 Electron micrograph of poxvirus. Vaccinia and smallpox were early su...
FIGURE 12 “1887–1987: A Century of Science for Health.” Illustration demonstra...
Chapter 5
FIGURE 1 Ross Granville Harrison. In 1907, Harrison reported the outgrowth of ...
FIGURE 2 Thomas Rivers. Rivers established laboratory studies of virological d...
FIGURE 3 FDR at Hill Top Cottage on his family’s estate in Hyde Park, NY. FDR,...
FIGURE 4 Polio poster. This fund‐raising poster shows a vigorous and fully int...
FIGURE 5 Frederick Robbins. John Enders, Thomas Weller, and Robbins received t...
FIGURE 6 CPE. The upper panel shows a monolayer of uninfected, human diploid f...
FIGURE 7 Harry Plotz. Colonel Harry Plotz (left) is shown receiving a World Wa...
FIGURE 8 Joseph Edwin Smadel. One of America's premier medical virologists, Sm...
FIGURE 9 Maurice Hilleman. America's premier vaccinologist, Hilleman was at th...
FIGURE 10 Edwin Herman Lennette. With an extensive background in the study of ...
Chapter 6
FIGURE 1 Werner and Gertrude Henle of CHOP. Werner Henle was the grandson of J...
FIGURE 2 G.‐D. Hsiung in the Section of Epidemiology and Preventive Medicine a...
FIGURE 3 G.‐D. Hsiung with the 1979 diagnostic virology class. Given annually ...
FIGURE 4 Chen Pien Li and Morris Schaeffer (seated) of the CDC. They are shown...
FIGURE 5 Walter Dowdle of the CDC. A distinguished virologist, Dowdle was with...
FIGURE 6 Charles Armstrong of the NIH. Armstrong made numerous contributions t...
FIGURE 7 Robert J. Huebner of the NIH. Although without formal scientific rese...
FIGURE 8 Robert J. Huebner (left) and Wallace Rowe of the NIH. Rowe made numer...
FIGURE 9 Robert Chanock (left) and Robert J. Huebner of the NIH. Chanock made ...
FIGURE 10 Coronavirus, negative‐contrast electron micrograph. The virus is nam...
FIGURE 11 W. Lawrence Drew championed the integration of virology into the mai...
Chapter 7
FIGURE 1 Sydney Brenner. With Robert Horne, Brenner developed negative stainin...
FIGURE 2 Robert Horne standing beside a poster showing the atomic lattice of g...
FIGURE 3 “The first electron micrographs of negatively stained bacteriophages,...
FIGURE 4 Adenovirus, negative stain. Negative staining allowed the demonstrati...
FIGURE 5 TMV prepared by Robert Horne using the Horne and Pasquali‐Ronchetti “...
FIGURE 6 June Almeida. With training at the technical level, Almeida went on t...
FIGURE 7 John Zahorsky, a pediatrician who first described “winter vomiting di...
FIGURE 8 Norovirus, a cause of acute viral gastroenteritis. Originally termed ...
FIGURE 9 Albert Kapikian. One of the members of the LID of the NIH recruited b...
FIGURE 10 Discoverers of rotavirus as the cause of acute infantile diarrhea. R...
FIGURE 11 Rotavirus in stool. This negative‐stained preparation shows the char...
FIGURE 12 Albert Coons, the originator of the FA staining technique. The techn...
FIGURE 13 Clinical specimen diagnosed as RSV by immunofluorescence. Rapid vira...
FIGURE 14 Phillip Gardner. With Joyce McQuillin, Gardner pioneered the use of ...
Chapter 8
FIGURE 1 Jaundice. Yellowing of the skin and the whites of the eyes can be an ...
FIGURE 2 F. O. MacCallum. A pioneer in diagnostic virology, MacCallum set up t...
FIGURE 3 Winston Churchill (left) with Franklin Delano Roosevelt (center) and ...
FIGURE 4 Baruch Blumberg. While seeking polymorphisms of proteins in human ser...
FIGURE 5 Rosalyn Yalow and Solomon Berson. Working as an intensely collaborati...
FIGURE 6 Creators of the ELISA, Eva Engvall and Peter Perlmann, and the EIA, A...
FIGURE 7 Creators of the Western blot, Harry Towbin and Julian Gordon. With T....
FIGURE 8 Immunoglobulin class responses to viral infection. This photo was tak...
FIGURE 9 Georges Kohler (previous page) and Cesar Milstein (this page), creato...
Chapter 9
FIGURE 1 Oswald Avery. Working at the Rockefeller Institute in New York City, ...
FIGURE 2 Erwin Chargaff. A Vienna‐educated biochemist working at the Columbia ...
FIGURE 3 Rosalind Franklin. A brilliant X‐ray crystallographer, Franklin took ...
FIGURE 4 Linus Pauling. Pauling's work on chemical bonds, including his text ...
FIGURE 5 Francis Crick (left) and James D. Watson. Working at the Cavendish La...
FIGURE 6 DNA double helix. This drawing demonstrates the essential features of...
FIGURE 7 Names Project AIDS Memorial Quilt on the National Mall in Washington,...
FIGURE 8 Françoise Barré‐Sinoussi (left) and Luc Montagnier (right). Working w...
FIGURE 9 Harald zur Hausen. Suspected for years to be of viral origin, cervica...
FIGURE 10 Kary Mullis. The PCR takes advantage of the capacity of short length...
FIGURE 11 Emerging viral epidemics. The appearance of a viral epidemic produce...
Chapter 10
FIGURE 1 Professor Zhang Yongzhen (center). With the assistance of colleague E...
FIGURE 2 Italian ICU nurse with bruises from masking. (Courtesy of Alberto Giu...
FIGURE 3 Diagram of the SARS‐CoV‐2 genome.
FIGURE 4 Diagram of SARS‐CoV‐2 virus particle (left) and spike protein recepto...
FIGURE 5 Professor Sharon Peacock. (Photo courtesy of Sharon Peacock.)
FIGURE 6 Barney Graham (left) and Jason McLellan (right). (Left panel courtesy...
FIGURE 7 Drew Weissman (left) and Katalin Karikó (right). (Courtesy of Penn Me...
FIGURE 8 Drive‐through sample collection tent for COVID‐19 testing. (Image cou...
FIGURE 9 Photo of adults looking at a family member through a nursing home gla...
FIGURE 10 Anthony Fauci (center), Director of the National Institute of Allerg...
Cover Page
Table of Contents
Title page
Copyright
List of Illustrations
Acknowledgments
Foreword
Preface
About the Authors
Begin Reading
Appendix: Chapter timelines
Glossary
Index
End User License Agreement
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JOHN BOOSS, MD
MARIE LOUISE LANDRY, MD
WITH MARILYN J. AUGUST, PHD
Copyright © 2023 American Society for Microbiology. All rights reserved.
Copublication by the American Society for Microbiology and John Wiley & Sons, Inc.
No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted by law. Advice on how to reuse material from this title is available at http://wiley.com/go/permissions.
The right of John Booss and Marie Louise Landry to be identified as the authors of this work has been asserted in accordance with law.
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While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties or merchantability of fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The publisher is not providing legal, medical, or other professional services. Any reference herein to any specific commercial products, procedures, or services by trade name, trademark, manufacturer, or otherwise does not constitute or imply endorsement, recommendation, or favored status by the American Society for Microbiology (ASM). The views and opinions of the author(s) expressed in this publication do not necessarily state or reflect those of ASM, and they shall not be used to advertise or endorse any product.
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Library of Congress Cataloging‐in‐Publication Data has been applied for
ISBN 9781683673736 (Paperback);
ISBN 9781683673743 (Adobe PDF);
ISBN 9781683673750 (e‐Pub)
Cover image: Specter of death waiting over Panama (U. J. Keppler, 1904). Courtesy of Beinecke Rare Book and Manuscript Library, Yale University.
Cover design: Debra Naylor, Naylor Design, Inc
In tribute to Gueh‐Djen (Edith) Hsiung, PhD, who is remembered for her pioneering contributions to the field of diagnostic virology, for training and inspiring generations of diagnostic virologists with her passion for virology, and for her social grace and generosity.
(Courtesy of Zhe Zhao.)
Chapter 1
1
Specter of death waiting over Panama (U. J. Keppler, 1904). Yellow fever, which had been termed “the American Plague,” struck Philadelphia in 1793. It later threatened the construction of the Panama Canal, as shown in this cover illustration for
Puck
, a political satire and humor magazine. (Courtesy of Beinecke Rare Book and Manuscript Library, Yale University.)
2
van Leeuwenhoek exhibiting his microscopes for Catherine of England (painting by Pierre Brissaud). Leeuwenhoek first described bacteria viewed through his early microscopes as “animalcules.” (Courtesy of the Abbott Historical Archives, Leeuenhoek exhibiting his microscopes for Catherine of England, 1939.)
3
Robert Koch, about 1908. Koch developed the methodology that allowed the emergence of bacteriology as a science. In addition, he isolated the bacteria of tuberculosis and cholera, age‐old scourges of humankind. (Courtesy of the National Library of Medicine.)
4
Martinus Beijerinck in his laboratory, May 1921. Beijerinck, like Ivanowski, demonstrated that tobacco mosaic disease could be transmitted by sap which had passed through bacteriological filters. He also demonstrated the need for living cells to replicate the disease‐causing factor, which he called
contagium vivum fluidum
.
5
Henry Rose Carter, 1909. As a member of the Marine Hospital Service, he was able to deduce a delay between primary and secondary cases of yellow fever. This extrinsic incubation period implied the need for another, nonhuman, host, later shown to be the mosquito. He was assigned to the Panama Canal Zone in 1904 to work on yellow fever. (Courtesy of Historical Collections & Services, Claude Moore Health Sciences Library, University of Virginia.)
6
George Miller Sternberg. Known as America's first bacteriologist, he produced the first textbook of bacteriology in the United States. He was Surgeon General of the Army from 1893 to 1902, during which time he appointed the Yellow Fever Commission. (Courtesy of the Historical Collections & Services, Claude Moore Health Services Library, University of Virginia.)
7
The Yellow Fever Commission consisted of (upper left) Walter Reed, who led the Commission; (lower left) James Carroll, who performed the filtration experiment; (upper right) Aristides Agramonte; and (lower right) Jesse W. Lazear, who became infected in the course of the experiments and died. In a remarkably brief period of time at the turn of the 20th century, the Commission under Reed demonstrated that the disease was transmitted by mosquitoes and that it could be transmitted by filtered blood and thus was caused by a virus. (Courtesy of the Historical Collections & Services, Claude Moore Health Sciences Library, University of Virginia, except for the image of Walter Reed, courtesy of The National Library of Medicine.)
Chapter 2
1
Mad Dog. The fear of rabid dogs has been portrayed throughout history. This caricature by T. L. Busby was published in London in 1826. (Courtesy Yale University, Harvey Cushing/John Whitney Medical Library.)
2
Louis Pasteur. Pasteur was one of the principal founders of germ theory. He disproved the theory of spontaneous generation; linked agricultural, animal, and human diseases to specific infections; and developed vaccinations, including that to prevent rabies. (Courtesy of the National Library of Medicine.)
3
Rabies prevention. The recognition that the Pasteurian treatment could prevent rabies after the bite of a rabid animal resulted in dramatic public acceptance. In this print from 1885, Pasteur is depicted observing the inoculation of a boy to prevent hydrophobia (rabies in humans). (Courtesy of the National Library of Medicine.)
4
Karl Landsteiner. Landsteiner was awarded the Nobel Prize in 1930 for the discovery of human blood groups. Another significant contribution was the demonstration that polio could be transmitted to monkeys by using spinal cord tissue from children who had died from the illness. (Courtesy of the Lasker Foundation.)
5
“Coughs and Sneezes Spread Diseases,” a slogan and poster campaign that was designed to cut down on the spread of respiratory diseases in the United Kingdom in World War II. Disease was portrayed as hampering the war effort at home. No doubt lurking in the minds of the Ministry of Health officials were the devastating effects of the 1919 influenza pandemic. (Courtesy of Yale University, Harvey Cushing/John Whitney Medical Library.)
6
L'influenza à Paris. This cover is from a Parisian weekly in 1890 during the influenza pandemic of 1889–1890. Originating in Russia and spreading westward, influenza became known as “Russian flu.” The cover depicts four scenes relating to the epidemic in Paris (clockwise from top left): a tent set up in a hospital courtyard, the interior of tent ward for the sick, the distribution of clothes to families of victims, and two men singing a new song,
“L’influenza, tout l’monde l’a!”
(“Influenza, Everyone Has It!”). (Courtesy of the National Library of Medicine.)
Chapter 3
1
Lady Mary Wortley Montagu. Lady Montagu, an aristocrat of considerable intellectual sophistication and beauty, brought the practice of variolation against smallpox to England from Turkey. It consisted of inoculating smallpox material and preceded Jenner's discovery of vaccination, the inoculation of cowpox to prevent smallpox. Lady Montagu is shown in a Turkish embellished costume with a jeweled turban in an illustration from
The Letters of Horace Walpole
. (Courtesy of the James Smith Noel Collection, Louisiana State University, Shreveport, LA.)
2
Edward Jenner. Jenner was an English physician with an intense interest in natural science. He demonstrated the truth in the folk belief that previous infection with cowpox prevented smallpox. The description of the inoculation of a boy, James Phipps, with material from a sore on the hand of a dairymaid, Sara Nelms, has achieved iconic status. Jenner published his results of vaccination in 1798. Vaccination eliminated the scourge of smallpox through the WHO Global Eradication Programme by 1979. (Courtesy of the National Library of Medicine.)
3
Triomphe de la Petite Vérole (Triumph of Smallpox). Vaccination was feared on the European continent as well as in England. This French caricature satirized that fear. It shows a woman with smallpox turning into a mermaid, a physician riding a cow, and an apothecary with a giant syringe pursuing frightened children. (Courtesy of the Wellcome Library, London, United Kingdom.)
4
Elie Metchnikoff. Metchnikoff's studies of phagocytosis initiated the science of immunology, specifically cellular immunity. With Paul Ehrlich, who developed the theoretical basis for the action of antibodies or humoral immunity, Metchnikoff received the Nobel Prize in 1908.
5
Jules Bordet. With his brother‐in‐law, Octave Gengou, Bordet demonstrated the fixation of complement by reacting with bacteria and immune serum. The complement was then no longer available to participate in a hemolysis reaction. The assay, known as complement fixation, became a mainstay of diagnostic virology by demonstrating the development of antibodies in serum after infection. Bordet received the Nobel Prize in 1919. (Courtesy of the National Library of Medicine.)
6
Complement fixation. In stage 1, complement, antigen, and antibodies are mixed together. If antibody is present for the antigen, complement will be bound (fixed). In stage 2, if the complement has been fixed in the first stage, it will be unavailable to combine with antibody‐coated erythrocytes. Therefore, a bull's‐eye pellet of cells will appear in the bottom of the tube, as shown on the bottom left. However, if complement has not combined with antigen and antibody in the first stage, it will be available to lyse antibody‐coated red cells. In that case, no bull's‐eye pellet will be seen at the bottom of the tube, as shown on the bottom right (53). (From
Diagnostic Virology
, courtesy of the author, Diane S. Leland, Indiana University School of Medicine.)
7
Neutralization test in tissue culture. In the first stage, antibodies and live virus are mixed together. In the second stage, the mixture is added to susceptible cells in tissue culture. If antibodies specific for the virus are present, no cytopathic effects will occur; otherwise, the cells will be attacked and reveal cytopathic effects, as shown on the right (53). (From
Diagnostic Virology
, courtesy of the author, Diane S. Leland, Indiana University School of Medicine.)
8
Hemadsorption. Tissue culture cells infected with certain viruses produce receptors with an affinity for red blood cells which attach to the surface and are visible microscopically. In this illustration, influenza B virus has infected rhesus monkey kidney cells, facilitating the specific attachment of red blood cells which outline only the virus‐infected cells. (Collection of Marilyn J. August.)
Chapter 4
1
Rudolf Virchow caricature. Virchow's
Cellular Pathology
revolutionized pathology, asserting that the cell is the fundamental focus of disease. Virchow helped facilitate the modern era of medicine yet was resistant to germ theory. (Courtesy of the National Library of Medicine.)
2
Advertisement for achromatic microscopes, 1859. Optical aberrations, including chromatic aberration, impaired image resolution into the 19th century. This advertisement, from
The Microscopist’s Companion: a Popular Manual of Practical Microscopy
, offers achromatic microscopes for sale in the second half of the 19th century. (Courtesy of the National Library of Medicine.)
3
Poster of a rabid dog. Perhaps the oldest recognized and most feared transmissible disease, rabies was often incorrectly diagnosed until the description of the Negri body in 1903. (Courtesy of the Historical Library, Yale University School of Medicine/The Wellcome Collection.)
4
Negri bodies in brain. The observation of intracytoplasmic inclusion bodies in the brains of animals was reported by Adelchi Negri in 1903. It became the diagnostic method of choice for decades. Arrows indicate Negri bodies in a brain tissue section. (Courtesy of J. H. Kim, Yale University School of Medicine.)
5
Varicella‐zoster virus inclusions in a monolayer of human diploid fibroblasts. Arrows indicate intranuclear inclusions in a field of multinucleated cells. Hematoxylin and eosin stain. (Collection of Marilyn J. August.)
6
Tzanck smear. Tzanck smears, performed at the bedside, offer a rapid diagnostic test of various skin lesions. For example, the presence of intranuclear inclusions suggests one of the herpes viruses, as in the example shown. (Collection of Marilyn J. August.)
7
Cytomegalovirus inclusions. Cytomegalovirus inclusions, originally thought to be parasitic in nature, identified cytomegalic inclusion disease of infants. This image is from the brain of a cytomegalovirus‐infected fetus. (Courtesy of J. H. Kim, Yale University School of Medicine.)
8
Bodo von Borries (left) and Ernst Ruska in the early 1930s on vacation on the island of Ruegen. (Courtesy of the Ernst Ruska Archive, Berlin, Germany.)
9
Max Knoll (left) and Ernst Ruska with an early transmission electron microscope, the 1933 Uebermikroskop. The photo was taken in the early 1940s. (Courtesy of the Ernst Ruska Archive, Berlin, Germany.)
10
Helmut Ruska, circa 1930. As the younger brother of Ernst Ruska and trained in medicine, Helmut Ruska pioneered the electron microscopy of viruses. Together with Ernst and his brother‐in‐law, Bodo von Borries, they published the first electron micrographs of viruses in 1939. This was the first visualization of the particulate nature of viruses. (Courtesy of Ernst Ruska Archive, Berlin, Germany.)
11
Electron micrograph of poxvirus. Vaccinia and smallpox were early subjects of electron microscopic study, and the brick shape was readily identified. This electron micrograph utilized more advanced techniques than were originally available, such as negative staining, allowing visualization of structural detail. (Courtesy of CDC‐PHIL [#2292]/Fred Murphy.)
12
“1887–1987: A Century of Science for Health.” Illustration demonstrating the armamentarium of research tools, including light and electron microscopes, experimental animals, and illustrative items. Each of the tools has been applied to the study and diagnosis of viruses and their infections. (Courtesy of the National Library of Medicine.)
Chapter 5
1
Ross Granville Harrison. In 1907, Harrison reported the outgrowth of nerve fibers from embryonic tissue
in vitro
. While Harrison did no further work with the technique, tissue culture was to transform many areas of biology. In years to come, tissue culture became the standard technique for virus isolation and identification. (Courtesy of the National Library of Medicine.)
2
Thomas Rivers. Rivers established laboratory studies of virological diseases at the Rockefeller Institute in New York City. He edited the first comprehensive textbook of clinical virology and rickettsiology in the United States. (Courtesy of Rockefeller Archive Center.)
3
FDR at Hill Top Cottage on his family’s estate in Hyde Park, NY. FDR, who experienced polio as an adult, is shown with his dog, Fala, and Ruthie Bie. The National Foundation for Infantile Paralysis, which FDR founded with his partner, Basil O’Connor, underwrote the costs of developing the Salk polio vaccine. Less well known is that the Foundation supported important investigations in basic science. (Courtesy of the Franklin D. Roosevelt Presidential Library and Museum, Hyde Park, NY.)
4
Polio poster. This fund‐raising poster shows a vigorous and fully intact, young boy striding toward the viewer. He is shown on a background featuring the same boy exhibiting polio, with a weak right leg, unable to hold his head upright, and with his left hand in a brace; footsteps lead from illness to health. (Photo provided courtesy of March of Dimes.)
5
Frederick Robbins. John Enders, Thomas Weller, and Robbins received the Nobel Prize in 1954 for the discovery of the capacity to grow poliovirus in tissue culture of nonneural origin. With Enders and Weller, Robbins demonstrated that CPE in tissue culture could be used to detect the growth of virus for isolation from clinical specimens, to measure the amount of virus present, and to determine the presence of antibodies. These crucial discoveries led to the rapid and widespread development of diagnostic virology laboratories. (Image 00716, property of Case Western Reserve University Archives.)
6
CPE. The upper panel shows a monolayer of uninfected, human diploid fibroblasts. The lower panel shows a focus of viral infection, described as CPE, marked by enlarged, rounded cells seen in the center of the photograph surrounded by normal, uninfected cells. CPE resulted from cytomegalovirus replication in the monolayer. (Courtesy of Diane S. Leland and Indiana Pathology Images.)
7
Harry Plotz. Colonel Harry Plotz (left) is shown receiving a World War II medal from Brigadier General George Callender. Plotz was the founding chief of the first virus and rickettsia lab set up primarily for diagnosis. It was established in January 1941 at the Walter Reed Army Medical Center. (From
Borden’s Dream
. Courtesy of the Borden Institute, Fort Detrick, MD.)
8
Joseph Edwin Smadel. One of America's premier medical virologists, Smadel directed the European Theater of Operations (ETO) virus and rickettsial diagnostic lab for the Army during World War II. On returning to the United States, he succeeded Harry Plotz as chief of the diagnostic lab at the Walter Reed Army Medical Center. (Courtesy of the Lasker Foundation.)
9
Maurice Hilleman. America's premier vaccinologist, Hilleman was at the Walter Reed Army Medical Center from 1948 until 1957. Among his accomplishments at Walter Reed, Hilleman described shifts in the antigenic nature of influenza viruses resulting in worldwide pandemics, and he isolated adenovirus from military troops. At the time of his death, he had created 8 of the 14 vaccines recommended for use in the United States. (Courtesy of the National Library of Medicine.)
10
Edwin Herman Lennette. With an extensive background in the study of numerous viruses, Lennette was designated the chief of the first state public health laboratory in the United States for viral and rickettsial diagnosis. He held the position in California from 1947 until retiring in 1978. With Nathalie J. Schmidt, he had a major role in establishing the field of diagnostic virology; he has been called “the father of diagnostic virology.” (Courtesy of Edwin Paul Lennette.)
Chapter 6
1
Werner and Gertrude Henle of CHOP. Werner Henle was the grandson of Jakob Henle, the anatomist. Werner and Gertrude Henle were trained in medicine in Germany and immigrated to the United States in 1936 and 1937, respectively. At CHOP, where Werner established a virology laboratory, they were affiliated with the University of Pennsylvania. They had long and productive careers in which they made contributions to basic and diagnostic virology. (Courtesy of the Fritz Henle estate.)
2
G.‐D. Hsiung in the Section of Epidemiology and Preventive Medicine at Yale University, 1959. Seen at the end of the front row on the right, she stands next to Robert Green, her long‐time colleague. Next to him is John Paul, the chairman and polio scholar. Dorothy Horstmann, with whom Hsiung established the diagnostic virology laboratory at the Yale New Haven Hospital a year later, is in the front row, third from the left. (Yale University, Harvey Cushing/John Hay Whitney/Medical Library.)
3
G.‐D. Hsiung with the 1979 diagnostic virology class. Given annually or biannually for many years, the diagnostic virology class was an intensive 2‐week course with lectures and hands‐on laboratory sessions. The photograph shows Hsiung (front row, center) and Kenneth McIntosh to her left, with students, faculty, and staff at the VAMC, West Haven, CT. The authors of the first and second editions of this book are pictured: John Booss (second row, right), Marilyn J. August (third row, left), and Marie L. Landry (last row, third from left). (Personal collection, Marilyn J. August.)
4
Chen Pien Li and Morris Schaeffer (seated) of the CDC. They are shown conducting polio research at the CDC location in Montgomery, AL, during a 1953 study. Schaeffer was the first director of CDC's virology labs from 1949 until 1959, when they were still in Montgomery. In 1959 the labs were moved to Atlanta, GA. (Courtesy of CDC‐PHIL [#2442], 1953.)
5
Walter Dowdle of the CDC. A distinguished virologist, Dowdle was with the CDC for 33 years and is a former deputy director. Among Dowdle's scientific interests are influenza, polio, HIV, and malaria. (Courtesy of CDC‐PHIL [#8374], 1986.)
6
Charles Armstrong of the NIH. Armstrong made numerous contributions to virology, including the understanding of polio, St. Louis encephalitis, and lymphocytic choriomeningitis. He was the first chief of the Division of Infectious Diseases at the NIH. Here he established the philosophy of the LID of fully working out an infectious disease process from agent isolation through prevention. (Courtesy of the National Library of Medicine.)
7
Robert J. Huebner of the NIH. Although without formal scientific research training, Huebner was hired by Charles Armstrong at the NIH. Huebner quickly demonstrated a remarkable capacity to grasp the fundamental concepts of epidemiology and laboratory virology and their application to human viral diseases. He became the leader of the LID. A man of diverse interests, he is shown here on his farm with a prize Angus bull. (Courtesy of the Office of History, NIH.)
8
Robert J. Huebner (left) and Wallace Rowe of the NIH. Rowe made numerous contributions to human virology and to experimental viral oncology. Among these contributions were the isolations of adenovirus and CMV. (Courtesy of the National Library of Medicine.)
9
Robert Chanock (left) and Robert J. Huebner of the NIH. Chanock made major contributions to the understanding of human viral respiratory disease, starting with the isolation of RSV. On Huebner's move to the NCI, Chanock took over as the leader of the LID. (Courtesy of the Office of History, NIH.)
10
Coronavirus, negative‐contrast electron micrograph. The virus is named for the corona‐like or crown spikes seen electron microscopically. This type of virus was first isolated from the human common cold using nasal and tracheal organ cultures. Magnification, approximately ×60,000. (Courtesy of CDC‐PHIL [#10270], Dr. Fred Murphy; Sylvia Whitfield, 1975.)
11
W. Lawrence Drew championed the integration of virology into the mainstream with the other divisions of the microbiology laboratory. Here he is examining tissue culture tubes in the microbiology laboratory at Mt. Zion Hospital and Medical Center in San Francisco in 1982. (Courtesy of University of California, San Francisco Library, UCSF Medical Center at Mount Zion Archives.)
Chapter 7
1
Sydney Brenner. With Robert Horne, Brenner developed negative staining to rapidly screen a large number of T‐even bacteriophage fractions by EM. It became a crucial tool in the investigation and classification of viruses. Brenner continued fundamental work in molecular biology, including the triplet nature of the genetic code and the demonstration of mRNA. He won a Nobel Prize in 2002 for the development of a unique model system with which to study organ development. (Courtesy of the Salk Institute for Biological Studies.)
2
Robert Horne standing beside a poster showing the atomic lattice of gold after optical linear integration of an electron micrograph of gold foil. Photograph taken by Alec Bangham, 1973. With Sydney Brenner, Robert Horne developed the technique of negative staining in a study of the components of a T‐even bacteriophage. This technique was to revolutionize the morphological study of all types of viruses. (Reprinted with permission from Harris JR, Munn EA. 2011.
Micron
42:528–530 [reference 136] © Elsevier, 2011.)
3
“The first electron micrographs of negatively stained bacteriophages, prepared by Bob Horne.” (Reprinted with permission from Harris JR, Munn EA. 2011. Micron 42:528–530 [reference 136] © Elsevier, 2011.)
4
Adenovirus, negative stain. Negative staining allowed the demonstration of subunit construction of viruses. With nucleic acid type, the architecture revealed by negative staining served as a basis for classification of viruses. (Photo by C. K. Y. Fong. Collection of Marilyn J. August.)
5
TMV prepared by Robert Horne using the Horne and Pasquali‐Ronchetti “Negative Staining‐Carbon Film technique” showing two‐dimensional paracrystalline/crystalline arrays of viruses. (Reprinted with permission from Harris JR, Munn EA. 2011.
Micron
42:528–530 [reference 136] © Elsevier, 2011.)
6
June Almeida. With training at the technical level, Almeida went on to receive a doctorate based on the body of her work. She pioneered the application of EM to clinical diagnosis, including IEM. (Courtesy of Joyce Almeida.)
7
John Zahorsky, a pediatrician who first described “winter vomiting disease.” He characterized the clinical characteristics of outbreaks as early as 1925. Later, the illness was called acute nonbacterial gastroenteritis. A characteristic outbreak in Norwalk, OH, in 1968, investigated by the CDC, resulted in the isolation of the Norwalk agent, soon imaged by Kapikian and colleagues. (Reprinted with permission from From the
Hills: an Autobiography of a Pediatrician
[52].)
8
Norovirus, a cause of acute viral gastroenteritis. Originally termed Norwalk agent, it was found by Albert Kapikian and colleagues at the NIH using antibodies to aggregate the virus by IEM. Kapikian had studied in the laboratory of June Almeida, where he learned the technique. (Courtesy of CDC‐PHIL [#10704], Charles D. Humphrey.)
9
Albert Kapikian. One of the members of the LID of the NIH recruited by Robert Huebner, Kapikian was to make seminal contributions to the understanding of viral gastroenteritis. He was the first to demonstrate the Norwalk agent to be a virus (norovirus), assisted in the demonstration of hepatitis A virus, and was one of the first investigators to demonstrate rotavirus associated with acute infantile diarrhea. Kapikian is shown seated (center) with Robert Chanock, seated on the left. (Courtesy of the NIH.)
10
Discoverers of rotavirus as the cause of acute infantile diarrhea. Ruth Bishop (left) of Melbourne, Australia, was the first to report the virus of infantile diarrhea by EM in biopsy samples of the duodenum. Thomas Flewett (middle) of Birmingham, England, established the presence of rotavirus in stool specimens by EM. Albert Kapikian of the NIH, Bethesda, MD (right), identified the virus by using IEM and conventional EM (see Fig. 9). (Courtesy of Graham Beards, under license CC BY‐SA 4.0.)
11
Rotavirus in stool. This negative‐stained preparation shows the characteristic wheel‐like appearance of rotavirus. The name was derived from the Latin rota, for “wheel.” (Collection of Marilyn J. August.)
12
Albert Coons, the originator of the FA staining technique. The technique identified antigens in tissues using antibodies tagged with compounds which would fluoresce under illumination by ultraviolet light. It allowed the development of rapid viral diagnosis. (Courtesy of the Lasker Foundation.)
13
Clinical specimen diagnosed as RSV by immunofluorescence. Rapid viral diagnosis was revolutionized with the implementation of immunofluorescence staining techniques. A sample collected on a swab from the nasopharynx was processed in the laboratory, and harvested cells were used to prepare a smear for staining. This is a direct immunofluorescent stain for RSV showing typical apple‐green staining in the cytoplasm of infected cells against a background of negative cells counterstained with Evans blue. (Courtesy of Indiana Pathology Images.)
14
Phillip Gardner. With Joyce McQuillin, Gardner pioneered the use of fluorescent‐antibody staining techniques for the rapid diagnosis of viral infections. He also played a crucial role in the creation of a group for the advancement of rapid viral diagnosis in Europe and encouraged a similar group in North America. He is shown here reviewing the book he coauthored with Joyce McQuillin. (Courtesy of Dick Madeley and June Almeida.)
Chapter 8
1
Jaundice. Yellowing of the skin and the whites of the eyes can be an indication of disease of the liver. Viral hepatitis, due to any of several agents, has been progressively defined as newer diagnostic techniques have been developed. In this photograph, yellowing of the sclerae (whites of the eyes) is evident. (Courtesy of CDC‐PHIL [#2860], Dr. Thomas F. Sellers, Emory University, 1963.)
2
F. O. MacCallum. A pioneer in diagnostic virology, MacCallum set up the first general virus reference laboratory in Britain at Colindale in 1946 and coauthored the textbook
Virus and Rickettsial Diseases of Man
in 1950. With G. M. Findlay, he made essential observations on homologous serum hepatitis and later devised the nomenclature which divided hepatitis into virus A (infectious) and virus B (homologous serum) hepatitis. (© Crown copyright. Reproduced with permission from the U.K. Health Security Agency, UKHSA.)
3
Winston Churchill (left) with Franklin Delano Roosevelt (center) and Joseph Stalin at Yalta in 1945. Previously, F. O. MacCallum was asked to offer an opinion as to whether Winston Churchill should receive immunization against yellow fever on a trip through the Middle East to Moscow. MacCallum counseled against the immunization, based on inadequate time for immunity to develop. He may have spared the Prime Minister exposure to hepatitis virus as a contaminant of the vaccine with potential consequences for impairing his capacity to lead the war effort. Courtesy of the National Archives, Local Identifier: 111‐SC‐260486, National Archives Identifier: 531340.
4
Baruch Blumberg. While seeking polymorphisms of proteins in human sera, he and his colleagues encountered a unique antigen which they termed the Australia antigen because of its origin from an Australian aborigine. It was later determined to be the key to unlocking the puzzle of a major type of serum hepatitis. (Image credit: NASA/Tom Trower.)
5
Rosalyn Yalow and Solomon Berson. Working as an intensely collaborative team, Yalow and Berson devised the RIA with the capacity to measure remarkably small amounts of antigen. It revolutionized many fields in biomedicine, including the capacity to measure the Australia antigen and the antibody against it. Yalow received the Nobel Prize alone in 1977, Solomon Berson having passed away in 1972.
6
Creators of the ELISA, Eva Engvall and Peter Perlmann, and the EIA, Anton Schuurs and Bauke van Weemen. Standing left to right: Engvall, Schuurs, Perlmann, and van Weemen with Johannes Buttner, President of the German Society of Clinical Chemistry. (Reprinted from Lequin RM. 2005.
Clin Chem
51:2415–2418 by permission of Oxford University Press.)
7
Creators of the Western blot, Harry Towbin and Julian Gordon. With T. Staehelin, Towbin and Gordon developed immunoblotting, or Western blotting. It combined the resolving power of electrophoretic separation of proteins in gels and the sensitivity of immunochemical reactions. Immensely useful in many scientific fields, the technique was applied to diagnostic virology, such as for diagnosis of HIV. In this photograph of Julian Gordon's group in 1979, Julian Gordon is center front and Harry Towbin is at the rear on the right. (Courtesy of Julian Gordon.)
8
Immunoglobulin class responses to viral infection. This photo was taken in 1998 at the 40th Anniversary of the World Reference Laboratory for FMD (foot‐and‐mouth disease) at the Institute for Animal Health, now The Pirbright Institute. It shows Fred Brown alongside the Institute's former Director, John B. Brooksby. With J. H. Graves, F. Brown determined that different types of antibodies developed in cattle at various times after infection with foot‐and‐mouth disease. Acute viral infections induce IgM, 19S antibodies, which are replaced later in the infection by IgG, 7S antibodies. (Courtesy of The Pirbright Institute.)
9
Georges Kohler (previous page) and Cesar Milstein (this page), creators of monoclonal antibodies. Despite what seemed to be insuperable theoretical barriers, Kohler and Milstein succeeded in fusing an antibody‐producing cell with a myeloma cell line. Refinements led to the capacity to produce enormous quantities of highly specific antibodies. The advent of monoclonal antibodies was a great boon to diagnostic virology. (Courtesy of the Lasker Foundation.)
Chapter 9
1
Oswald Avery. Working at the Rockefeller Institute in New York City, Avery demonstrated that transmission of a heritable characteristic was conveyed by DNA. Exacting studies published in 1944 with Colin MacLeod and Maclyn McCarty determined the nucleic acid basis of the transformation of pneumococcal colonies. It was a finding in advance of its time. (Courtesy of the Rockefeller Archive Center.)
2
Erwin Chargaff. A Vienna‐educated biochemist working at the Columbia University College of Physicians and Surgeons, Chargaff had immediately understood the implications of Avery's work. He determined that the purine and pyrimidine bases composing nucleic acids had reproducible ratios. These findings became known as Chargaff's Rules, which defined base complementarity, a fundamental characteristic of heredity. (Courtesy of the Archives of Columbia University Medical Center and the National Library of Medicine.)
3
Rosalind Franklin. A brilliant X‐ray crystallographer, Franklin took photographs of DNA which provided the crucial pieces of data to decipher its structure. They demonstrated that DNA was a two‐chain helical structure with the chains oriented in opposite directions. (From the National Portrait Gallery. Photo credit: Vittorio Luzzati.)
4
Linus Pauling. Pauling's work on chemical bonds, including his text
The Nature of the Chemical Bond
(published in 1939), laid the basis for modern chemistry. For this work he won the Nobel Prize in 1954. His entry with Robert Corey in 1953 into the race to discover the structure of DNA, while flawed, accelerated Watson and Crick's work to fit the pieces of evidence together. (Courtesy of Ava Helen and Linus Pauling Papers, Oregon State University Libraries.)
5
Francis Crick (left) and James D. Watson. Working at the Cavendish Laboratories at Cambridge University, Watson and Crick determined the structure of DNA. Published in an elegant, brief paper in
Nature
in 1953, it provided the molecular structural basis to understand heredity. (Courtesy of the James D. Watson Collection, Cold Spring Harbor Laboratory Archives.)
6
DNA double helix. This drawing demonstrates the essential features of paired DNA strands: a backbone of sugars and phosphate groups, linked by bases pairing from opposite strands, and the strands coiled around each other oriented in opposite directions. Base pairing underlies the capacity to copy strands, that is, to reproduce genetic information. (Courtesy of the National Human Genome Research Institute.)
7
Names Project AIDS Memorial Quilt on the National Mall in Washington, DC. The quilt is a massive memorial to individuals who have lost their lives to AIDS‐related causes. (Courtesy of the National AIDS Memorial, http://www.aidsmemorial.com.)
8
Françoise Barré‐Sinoussi (left) and Luc Montagnier (right). Working with clinicians who were attempting to find the cause of AIDS, Montagnier and Barré‐Sinoussi at the Pasteur Institute in Paris found a retrovirus in a lymph node biopsy. Ultimately shown to be the cause of AIDS, the virus was to be called human immunodeficiency virus (HIV). Montagnier and Barré‐Sinoussi were awarded the Nobel Prize in 2008 for their discovery. (Photos courtesy of Institut Pasteur. Photo credit: François Gardy.)
9
Harald zur Hausen. Suspected for years to be of viral origin, cervical cancer was demonstrated to be associated with HPV by zur Hausen. He had pioneered work with nucleic acid hybridization to detect viruses in clinical specimens of human tumors. He was awarded the Nobel Prize in 2008 for his discovery that HPVs cause human cervical cancer. (Courtesy of Harald zur Hausen, DKFZ, Heidelberg.)
10
Kary Mullis. The PCR takes advantage of the capacity of short lengths of nucleotides to find and hybridize with reciprocal pieces of nucleic acid. Once hybridized, multiple copies are made through repeating cycles of polymerase‐assisted replication. PCR has transformed many fields in biology, including, notably, the capacity to discover minute amounts of viruses in clinical samples. Kary Mullis devised the process while driving one evening in 1983 and was awarded the Nobel Prize in 1993. (Courtesy of Dona Mapston, under license CC BY‐SA 3.0.)
11
Emerging viral epidemics. The appearance of a viral epidemic produces fear and panic as well as sickness and death. Next‐generation sequencing (NGS) would provide the key to the rapid identification of SARS‐CoV‐2, as detailed in the next chapter. This political cartoon of 1919 by Charles Reese shows the panic of people rushing to get a “goode germ destroyer” in the context of the influenza pandemic. (Courtesy of the National Library of Medicine.)
Chapter 10
1
Professor Zhang Yongzhen (center). With the assistance of colleague Edward Holmes, he uploaded the genome sequence of what became known as SARS‐CoV‐2 for the global community of scientists. (Courtesy of GigaScience, under license CC BY.)
2
Italian ICU nurse with bruises from masking. (Courtesy of Alberto Giuliani, under license CC BY‐SA 4.0.)
3
Diagram of the SARS‐CoV‐2 genome.
4
Diagram of SARS‐CoV‐2 virus particle (left) and spike protein receptor binding domain (RBD) binding with ACE‐2 receptor on host cell (right). (Modified from Min L, Sun Q. 2021.
Front Mol Biosci
8:671633. © 2021 Min and Sun.)
5
Professor Sharon Peacock. (Photo courtesy of Sharon Peacock.)
6
Barney Graham (left) and Jason McLellan (right). (Left panel courtesy of NIAID. Photo credit for right panel: Vivian Abagiu/University of Texas at Austin.)
7
Drew Weissman (left) and Katalin Karikó (right). (Courtesy of Penn Medicine.)
8
Drive‐through sample collection tent for COVID‐19 testing. (Image courtesy of Michelmond, Shutterstock ID: 1705973104).
9
Photo of adults looking at a family member through a nursing home glass door. (Photo credit: Don Knight,
The Herald Bulletin
, Anderson, IN.)
10
Anthony Fauci (center), Director of the National Institute of Allergy and Infectious Diseases. He is shown with former President Clinton (right) and former Vice President Gore (left). (Courtesy of NIAID, under license CC BY 2.0.)
The challenges in writing the history of the COVID‐19 pandemic for this second edition have differed considerably from the challenges of writing the first edition. First have been the time spans. The viral infections and their diagnostics of the first edition (which comprise chapters 1–9 in the second edition) cover roughly a century, whereas the covered history of COVID‐19 at the time of writing is about two and a half years. As a consequence, the sources used have differed considerably. Archived materials, edited books, monographs, and journals covering extended periods were examined for the viral infections in chapters 1–9. Narrative research on COVID‐19 and its virus, SARS‐CoV‐2, has relied on contemporaneous sources. These have included prepublication reports online of reviewed and accepted journal articles, studies published online prior to peer review, and online reports from trusted news media. For example, experienced scientific and medical journalists of The New York Times and The Washington Post often have had access to emerging findings. The reader could then read the original investigation's findings through hyperlinks in online articles. Traditional print copies of newspapers, scientific and medical journals, and books continued to play an important role. Underpinning these resources has been M.L.L.'s role of directing a major university hospital's diagnostic virology laboratory.
The second difference has been the restrictions imposed by the pandemic. For the first edition, travel and meetings for interviews were unimpeded by concerns of infection. During the time of COVID‐19, lockdowns, travel restrictions, and concern about contracting infection interfered with such meetings.
An experience common to both editions has been the strong and expert support of our efforts by the leadership and editorial staff at the ASM Press. For the first edition, Jeff J. Holtmeier, the Director of ASM Press at the book's inception, guided the development of the concept and provided patient encouragement. Christine Charlip, his successor, encouraged us to enlarge the audience from one that was primarily technical in orientation to one with broad interests in science and medicine. John Bell, the production editor, facilitated that shift. Artist Debra Naylor collaborated on the book's cover design.
Christine Charlip initiated the project of the second edition and provided encouragement at key points. Megan Angelini took on the role of managing developmental editor. She efficiently facilitated our work and added features, substantively adding to the value of the book. We are grateful to her and to Lindsay Williams, editorial rights specialist, for locating and gaining permission for use of figures in all chapters of the new edition.
Credit must go to laboratorians for doing the fundamental work of virological diagnosis, public health professionals for policies and practices that protect the public during the pandemic, health care workers for acute and chronic care of patients sick with COVID‐19, and basic and clinical researchers for the critical work of figuring out how the disease works, how to treat it, and how to prevent it.
We are indebted to Professors Richard L. Hodinka, Irving Seidman, and Frank M. Snowden for providing in‐depth expert reviews of the manuscript for the second edition as it was being developed. We are grateful to Frank Bia and Jung H. Kim for expert focused input. In a chance meeting, David Tkeshelashvili reminded J.B. of one of his core teachings. We are, of course, responsible for errors of fact, interpretation, and omission which remain.
Our thanks continue to extend to all those who contributed to the writing of the first edition, particularly Warren Andiman, Jangu Banatvala, Edward A. Beeman, Leonard N. Binn, F. Marilyn Bozeman, Irwin Braverman, Charlie Calisher, Dave Cavanagh, Gustave Davis, Walter Dowdle, Bennett L. Elisberg, Margaret M. Esiri, Durland Fish, Bagher Forghani, Harvey Friedman, D. Carleton Gajdusek, J. Robin Harris, David L. Hirschberg, Richard L. Hodinka, Robert Horne, Albert Z. Kapikian, Robert J. T. Joy, Edwin D. Kilbourne, Jung H. Kim, Diane S. Leland, W. Ian Lipkin, Dick Madeley, Kenneth McIntosh, Michael B. A. Oldstone, Stanley Plotkin, Morris Pollard, Philip K. Russell, Karen‐Beth G. Scholthof, Gregory Tignor, and Alex Tselis.
Historians and curators are the guardians of the traces of our past, and several provided indispensable help for the first edition. At Yale they included Toby Appel, Melissa Grafe, Frank Snowden, and Susan Wheeler. Elsewhere, Steven Greenberg, Col. Richard C. V. Gunn, Sally Smith Hughes, and Sarah Wilmot provided invaluable guidance. Translations of scientific papers in French and German were essential. Mary Ann Booss and Brigitte Griffith offered expert advice in translating scientific publications in French, while Carolin I. Dohle provided expert translations of scientific publications in German.
A number of individuals helped to secure especially difficult‐to‐find figures or provided critical help in developing the first edition's manuscript. Zhe Zhao, Dr. Hsiung's grandniece, was kind enough to provide the portrait used with the dedication in both editions. Special thanks are extended to Paul Theerman and Ginny A. Roth at the National Library of Medicine for providing many high‐resolution images from the library collection. Others included Joyce Almeida, Debbie Beauvais, Claire Booss, Robert B. Daroff, John and Donna Jean Donaldson, Will Fleeson, Emma Gilgunn‐Jones, Tina Henle, Albert Z. Kapikian, David Keegan, Edwin Paul Lennette, Rich McManus, Venita Paul, Thomas Ruska, and Irving Seidman.
It seemed particularly important to gain an understanding of the first diagnostic virology and rickettsiology lab established anywhere. It was established in January 1941 at the Walter Reed Army Medical Center. In investigating the establishment and operation of that laboratory for the first edition, we had exceptional support from committed and knowledgeable personnel. We extended special thanks to Michael P. Fiedler, research librarian, Andrew H. Rogalsky, archivist, and Leonard N. Binn, whose career in virology at Walter Reed spanned over five decades. The first diagnostic virology and rickettsial lab in the U.S. civilian sector was at the State of California Public Health Labs. We are grateful to Bagher Forghani for generously and graciously providing a full understanding of that very important lab and its leaders.
For the first edition, M.J.A. was continually cheered by her dear, now late father, Ralph August, by friends near and far away, and by her Let's Look at Art docent colleagues at the San Jose Museum of Art. Through the second edition and the pandemic, she has also been inspired by her friends and colleagues at Art Yard BKLYN.
M.L.L. was grateful to be able to contribute to the unprecedented virology laboratory efforts necessitated by the COVID‐19 pandemic, and to share some of those experiences in this book. Through two years of recurring testing challenges, she was buoyed as always by the support, wise counsel, and optimism of her husband, children, and grandchildren.