A History of Experimental Virology

By their powers of reason scientists will be able to extract from nature the answers to their questions. From: Critique of Pure Reason, 1781 Immanuel Kant (1724-1804), German Philosopher History is a composite of stories. The history of the biological disciplines has been written by all those who opened the gates of new knowledge by generating ideas and the experiments to support them. Previous authors have attempted various approaches to the history of virology, as is reflected in the numerous books and book-series issuing from the publishing houses. This volume is an attempt at a compre­ hensive yet compact survey of virology, which has meant penetrating the rigid limits of the separate disciplines of biology in which virologists have worked. Writing this history of experimental virology was really a search for the origins and for vital signposts to portray the wide scope of the knowledge attained thus far. This was done in com­ plete awareness of the fact that every presentation depends heavily upon the perspective of the observer, and of necessity communi­ cates only a part of the whole. The present scientific story hopes to recount the most important knowledge achieved during this past century - the first century of the exciting developments in virology.

1 2000 Years Preceded the Emergence of Experimental Virology.- 1.1 Antiquity and the Origin of the Plague.- 1.2 The Cornerstones of Generatio Spontanea Begin to Quake.- 1.3 The Germ Theory is Born and Proven.- 1.4 The Germ Theory Crystallizes into the Germ Doctrine.- 1.5 The Theoretical and Experimental Basis of the Germ Doctrine at the End of the 19th Century.- 1.5.1 Theoretical Basis.- 1.5.2 Experimental Basis.- 2 Microscopes and Culture Media Fail.- 2.1 The Virus and Koch’s Postulates.- 2.1.1 The Use of the Term “Virus”.- 2.1.2 Koch’s Postulates.- 2.1.2.1 “Koch’s Postulates” Do Not Exist!.- 2.1.2.2 Reliable Recognition of Pathogens Using Koch’s Proof.- 2.2 A New Type of Pathogenic Agent?.- 2.2.1 The Discussion Begins.- 2.2.1.1 Tobacco Mosaic Disease (TMD).- 2.2.1.2 Foot-and-Mouth Disease (FMD).- 2.2.1.3 Bovine Pleuropneumonia.- 2.2.1.4 Rabbit Myxomatosis.- 2.2.1.5 African Horse Sickness.- 2.2.1.6 Fowl Plague.- 2.2.1.7 Yellow Fever.- 2.2.2 The Pathogen Remains While the Definition of the Virus Changes.- 2.2.2.1 Invisible Microbes.- 2.2.2.2 Non-Culturable Microbes.- 2.2.2.3 Filterable Microbes.- 2.2.3 The Filterable Viruses are Recognized.- 2.2.4 Who was the Founder of Virology?.- 3 Are Filterable Viruses Miniscule Bacteria?.- 3.1 The Use of Physical Methods.- 3.1.1 Filtration.- 3.1.2 Centrifugation.- 3.1.3 Adsorption.- 3.1.4 Electrophoresis.- 3.1.5 Optical Methods.- 3.2 Biochemical Investigations with Filterable Viruses.- 3.3 Are Cell Inclusions Specific to Filterable Viruses?.- 3.4 Culturing Filterable Viruses In Vivo and In Vitro.- 3.4.1 The Search for Experimental Animals.- 3.4.2 Is “Pure Culture” of Filterable Viruses Possible?.- 3.5 Filterable Viruses as Antigens.- 3.5.1 Neutralization Tests.- 3.5.2 Aggregation Tests.- 3.5.2.1 Agglutination and Precipitation.- 3.5.2.2 Complement-Fixation Reaction (CFR).- 3.5.3 Immunity and Immunization.- 3.5.3.1 Immunity.- 3.5.3.2 Passive Immunization.- 3.5.3.3 Active Immunization.- 3.6 Filterable Viruses as Pathogens.- 3.6.1 Infectious Diseases Caused by Viruses.- 3.6.2 Tumour Development.- 3.7 Viruses are not Just Very Small Bacteria.- 3.7.1 Linking Virus Reproduction to Living Cells.- 3.7.2 Viruses are Autonomous, Organized Particles.- 4 On the Way to a Definition of the Virus.- 4.1. Viruses as Pathogens.- 4.1.1 New Knowledge about Animal Viruses.- 4.1.1.1 First Contact With a Virus.- 4.1.1.2 Tissue and Organs In Which Cell Infection is Initiated.- 4.1.1.3 Secondary or Generalized Symptomatic Infections.- 4.1.1.4 Uncommon Interactions Between the Virus and the Host Organisms.- 4.1.1.5 Tumour Virus Infections.- 4.1.1.6 Interference.- 4.1.1.7 Immunological Problems.- 4.1.1.8 Immunization.- 4.1.2 Disease-Producing Insect Viruses.- 4.1.2.1 Inclusion Diseases.- 4.1.2.2 Non-Inclusion Diseases.- 4.1.3 Virus Diseases in Higher Plants.- 4.1.3.1 First Contact With a Virus.- 4.1.3.2 Intracellular Virus Multiplication.- 4.1.3.3 The Spread of Viral Plant Diseases.- 4.2 A Biochemical Approach to the Virus.- 4.2.1 The Morphology and Size of Viruses.- 4.2.2 The Biochemistry of Viruses.- 4.2.2.1 Nucleic Acids.- 4.2.2.2 Proteins.- 4.2.2.3 Virus Enzymes and Other Substances.- 4.2.3 The Structure of Viruses.- 4.2.3.1 Plant Viruses.- 4.2.3.2 Enteroviruses.- 4.2.3.3 Complex, Medium-sized Animal Viruses.- 4.2.3.4 Complex, Larger Animal Viruses.- 4.2.3.5 Bacteriophages.- 4.3 Viruses as Genetic Macromolecules.- 4.3.1 The Genetics of Bacteriophages.- 4.3.2 Plant Virus Mutants.- 4.3.3 The Genetics of Animal Viruses.- 4.4 What Exactly is a Virus?.- 5 The Period of Biochemistry and Molecular Genetics.- 5.1 The Virion.- 5.1.1 Virion Morphology and Capsid Symmetry.- 5.1.2 Virion Structure.- 5.1.2.1 The Biochemical Structure of the Virion.- 5.1.2.2 The Molecular-Genetic Structure of Virions.- 5.1.3 The Taxonomy and Classification of Viruses.- 5.2 The Virus Multiplication Cycle.- 5.2.1 Adsorption.- 5.2.2 Uptake by the Cell.- 5.2.3 Uncoating.- 5.2.4 The Synthesis Phase.- 5.2.4.1 DNA Viruses.- 5.2.4.2 RNA Viruses.- 5.2.4.3 Retroviruses.- 5.2.4.4 Hepadnaviruses.- 5.2.5 Virus Assembly.- 5.2.6 Virus Maturation.- 5.2.7 Virus Release.- 5.3 Viruses as Pathogens.- 5.3.1 Acute Virus Infections.- 5.3.1.1 Animal Viruses.- 5.3.1.2 Plant Viruses.- 5.3.2 Inapparent Virus Infections.- 5.3.2.1 Persistent Infections.- 5.3.2.2 Latent Infections.- 5.3.3 Slow Virus Infections.- 5.3.3.1 Slow Infections Caused by Viruses.- 5.3.3.2 Slow Infections Caused by Unconventional Agents.- 5.3.4 Viruses and Tumours.- 5.3.4.1 In Vitro Tests.- 5.3.4.2 Virus-Specified Proteins in Tumours and Transformed Cells.- 5.3.4.3 Genes and Their Products in Cell Transformation.- 5.3.4.4 Results on Some DNA (Tumour) Viruses.- 5.3.4.5 Results with RNA Tumour Viruses.- 5.4 Viruses and Immunity.- 5.4.1 Humoral and Cell-Mediated Immunity as Parameters of Protection.- 5.4.2 The Diagnosis of Virus Infection.- 5.4.3 Immunoprophylaxis in Virus Infections.- 5.5 Viral Pathogenicity.- 5.5.1 Histological and Anatomical-Pathological Effects.- 5.5.1.1 Teratogenic Virus Effects.- 5.5.1.2 Mutagenic Virus Effects.- 5.5.1.3 Virus Diseases Dependent on Virus-Induced Defects of the Immune System.- 5.5.2 Molecular-Genetic Assessment of Virus Pathogenicity.- 5.5.2.1 Cell and Tissue Tropism.- 5.5.2.2 Virulence and Attenuation.- 5.5.2.3 Latency.- 5.6 Virus Chemotherapy.- 5.6.1 The Antibiotic Phase.- 5.6.2 The Anti-metabolite Phase.- 5.6.3 Will the Molecular-Genetic Approach Help?.- Epilogue.- Name Index.