EXPERIMENTAL LEUKEMIA:HISTORY, BIOLOGY AND GENETICS -- Contents -- Preface -- Background of ExperimentalLeukemia Research -- Abstract -- 1.1. Classic Pathology -- Cancer Theories of Rudolf Virchow (1858) and Julius Cohnheim (1878) -- Hansemann's Anaplasia Concept of Cancer (1893) -- Boveri Predicted Chromosome Functions and proposed Cancer Theory -- Experimental Pathology in the Golden Period -- 1.2. Classic Cancer Biochemistry, 1920-1970 -- High Aerobic Glycolysis in Tumors (Warburg, 1930) -- Greenstein's Convergence Theory (1956) -- Metabolic Shift in Hepatomas with Different Growth Rates (Weber, 1965) -- 1.3. Concept of Gene 1940-1970 -- DNA as the Genetic Element -- 1.4. Cell and Genome Analysis 1950-1980 -- Tissue Culture -- Chromosome Analysis -- New Chromosome Techniques -- Nucleic Acid Hybridization (1961) -- Discovery of Restriction Enzymes -- Recombinant Technique and Plasmid Technology -- Routine Biotechnology Methods -- Monoclonal Antibodies Technique and PAP Method -- 1.5. Discoveries in Retroviral Oncology Started in1960 -- Discovery of src Gene -- Discovery of c-src -- Insertional Mutagenesis -- Discovery of ras Mutations in Human and Animal Cancers -- Rearranged myc and abl at the Translocation Breakpoints -- 1.6. Oncogenic DNA Viruses -- Shope Papilloma Virus -- Lucké Frog Kidney Carcinoma -- Polyoma Virus -- Simian Vacuolating Virus 40 (SV40) -- Adenoviruses -- 1.7. Computers and Gene Mapping -- Computer and DNA Databases -- Gene Mapping -- 1.8. DNA Data Bases and Genome Projects -- Genome Projects and DNA Database -- 1.9. New Genetic Leukemia Models -- Induction -- Transgenic Leukemia Models and Clone Animal Models -- Bcr/abl Chimeric Mouse -- Other Leukemia Models -- Clone Mouse and Rat -- 1.10. Merits of Experimental Leukemia Research -- 1.11. "Business of Discovery", a CumulativeChain Process of Hypothesis and Evidence.

Experimental Animal Models vs. Mechanism Studies -- Creative Works in Experimental Leukemia -- Summary -- Early History of LeukemiaResearch -- Abstract -- 2.1. Discovery of Human Leukemia -- Leukemia was First Described by Bennett and Virchow in 1845 -- The Bennett's Case -- The Virchow's Case -- Leukemia or Leukocythemia? -- Leukemia, Neoplasm or Infectious Disease? -- Priority of Reports -- Splenic versus Myelogenous Leukemia (Neumann, 1869) -- Modern Hematology Methods by Paul Ehrlich (1877) -- Blood-forming Organs -- Another Earliest Record of Human Hematological Malignancy by ThomasHodgkin (1832) -- Hodgkin Disease was rediscovered by Samuel Wilks (1865) -- Thomas Hodgkin as an Philanthropist -- 2.2. Spontaneous Animal Leukemia and Venereal"Lymphosarcoma" -- Experimental Inoculation of Human Leukemia -- Early Descriptions of Leukemia in Animals -- Transmissible Venereal Tumor (TVT) -- TVT Distributed Worldwide -- The Name of Sticker's Tumor -- 2.3. Avian Leukosis -- Definition -- Avian Leukosis- Early Reports by Butterfield (1905) and Kon (1907) -- Moor's infectious leukemia -- Butterfield Case of Aleukemic Lymphadenoma (1905) -- Mohler's Leukemia Cases (Butterfield, 1905) -- Kon's Case (1907) -- The First Cell-free Transmission by Ellermann and Bang in 1908 -- Leukemia and Pseudoleukemia -- Two Primary Cases were Myeloblastosis -- Cell and Cell-free Inoculation -- Various Hematological Types of Avian Leukemia -- Multipotentiality of Single Virus? -- Identification of Various Disease Types -- Avian Leukosis as a Disease Complex -- Progress in Classification of ASLV -- Isolation of Substrains of Avian Leukosis Viruses -- Avian Leukosis Tumor Spectrum -- Biochemical and Immunological Studies on Virus Components -- 2.4. Rous Sarcoma -- Preceded and Contemporary Research -- Peyton Rous -- Establishment of Rous Sarcoma (1910) -- Inoculation.

Serial passage -- Discovery of RSV (Rous, 1911) -- Given-up in 1915 and Returned in 1934 -- Virus Theory of Cancer in 1930-1950 -- Development of RSV Studies -- Studies on RSV by Electron Microscopy -- Focus Assay for RSV (1958) and AMV (1961) -- Interference and Host Range (1964) -- Group-Specific Antigen -- Substrains of RSV with Extended Host Range -- 2.5. Fujinami Sarcoma Another Avian SarcomaStrain -- Akira Fujinami -- Preventive Work of Worm Disease -- Fujinami Chicken Sarcoma -- Originated from a Samurai Society -- Same Time with Peyton Rous (1910) -- Cell-Free and Heterologous Transfer -- Severe Criticism Waited -- Fujinami Virus Revived -- Sarcoma was Sent Dried to Gye in London (1931) -- From Bratislava to Rockefeller Institute -- 2.6. Marek Disease -- Definition -- Original Description as Polyneuritis by Marek (1909) -- Renamed Neural Lymphomatosis by Pappenheimer (1929) -- Pathology, Symptom and Epidemiology -- Endemic and Epidemic Spread -- Detection of Transmitting Agent -- A Virus Named MDV -- Feather Follicular Cells are the Source of MDV -- Vaccination against MD -- Virulent Virus Strains Attenuated by Tissue Culture Passage -- Vaccines Prepared from Avirulent Viruses -- Vaccines Containing Herpesvirus Isolated from Turkeys -- Summary -- 2.7. Development of Inbred Mice -- Inbred Mouse -- William Castle -- The First Mendelian Geneticist in USA -- The Bussey Institute at Harvard -- Abbie Lathrop -- Started from Fancy mice -- Japanese Waltzing Mice -- From Fancy Mice to Laboratory Mice -- Clarence C. Little -- The First Pure Strain of Mice, DBA -- Cancer Heredity, Co-working with Tyzzer -- After the Military Service -- Leukemic Strain C58 of MacDowell (1930) -- The Jackson Laboratory -- Important Mouse Strains Used in Leukemia Research -- 2.8. Jacob Furth and Mouse Strain Ak AKR -- Jacob Furth's Life.

Early Years in Research, 1918-1932 -- A Turning Point -- Leukemia Research -- Why Mouse Leukemia? -- Origin of Ak strain -- Irradiation -- Establishment of Leukemic Ak Strain -- Mrs Rhoades and Clara J. Lynch, from Ak to AKR -- The Incidence of Spontaneous Leukemia -- Pathology of AKR Lymphoma -- Susceptibility of hybrid AKR Mice -- 2.9. Search for Leukemia Virus (Ludwik Gross) -- Cell-Free Transfer Experiment in Mice -- The Life of Ludwik Gross (1904-1999) -- A Single Room Lab at the Basement of VA Hospital -- Discovery of Gross Virus -- Start of the Gross' Leukemia Work -- Disappointing and Time-consuming Project Continued -- Newborn Animals Took Better -- Cell-free Transmission of Mouse Leukemia to Newborn and Suckling Mice -- Viral Nature of AKR Leukemia -- Vertical Transmission -- The First Report in 1951 was not Fully Accepted -- Criticism Gradually Disappeared by 1958 -- Passage-A Virus -- Isolation of Passage-A Virus (1957) -- Cell-Free Transmission with Passage-A Confirmed in Other Laboratories -- Discoveries of Many Other Experimental Leukemia/Sarcoma Viruses -- Summary -- 2.10. Early Histrory of Chemical Leukemogenesis -- 2.10.A. Early History of Chemical Carcinogenesis -- Percivall Pott (1775) -- Tar Cancer by Yamagiwa and Ichikawa (1915) -- Carcinogenic Aromatic Hydrocarbons -- Synthesis of 3,4-BP (1933) and 3-MC (1936) -- Synthesis of 7,12-DMBA and 7,812-TMBA (1938) -- Iball Index (1939) -- Carcinogenic Aromatic Amines -- Azo Dyes -- Nitrosamines and Nitrosoureas -- 2.10.B. Some Landmarks in Chemical Carcinogenesis Studies before1970s -- Two-Step Theory of Carcinogenesis Proposed by Berenblum (1941) -- Initiation and Promotion Stage of Carcinogenesis -- Promoters in Croton Oil and PKC -- Metabolic Activation of Chemical Carcinogens (Millers, 1940-1970) -- Wisconsin Group -- The Millers' Contribution -- Two Important Discoveries.

Epigenetic Theory of Carcinogenesis -- DNA Target Theory -- The Epigenetic Theory Still Alive? -- Proximate and Ultimate Carcinogens -- Epoxide Hypothesis -- Drug Metabolizing Enzymes -- Microsomal Fractions -- Phase I and Phase II -- In vitro Transformation by Leo Sachs (1963) -- PAHs and X-rays Transform Cells in Vitro -- Chromosome Balance Decides Malignancy -- Ames Test (1973) -- Evidences for Carcinogen-Induced Gene Mutation -- Useful for Carcinogen/Mutagen Screening -- Further Progress -- 2.10.C. Chemically-Induced Rodent Leukemia -- An Early History -- The Earliest Induction Experiments of Chemical Leukemia -- Attempt of Berenblum and Furth -- Estrogen, 2-AAF, 3-MC -- DMBA, Urethane, and Nitrosoureas -- Summary -- 2.11. Experimental Studies on RadiationLeukemia -- 2.11.A. History of Radiation Hazards -- Discovery of X-ray (1895) and Radium (1898) -- Other Historical Radiation Hazards -- Leukemogenic Effect of Ionizing Radiations -- 2.11.B. Experimental Induction of Leukemia in Mice by X-rays -- Early Studies -- 2.11.C. Kaplan and Brown Method (1952) -- Modifying Factors on Radiation Leukemogenesis -- 2.11.D. The Viral Nature of Radiation-Induced Leukemia in Mice -- Cell-Free Transmission Experiments in C3H Mice by Gross: Passage-X -- Serial Cell-Free Passage -- Leukemia Types -- Cell-free Transfer by Lieberman and Kaplan in C57BL/ mice (1959) -- The Experiments by Other Researchers -- Leukemogenic Virus from Mice of the RF Strain -- Electron Microscopic Studies of Radiation-Induced Leukemia in Mice -- Rad-LV is Different from Gross MLV? -- Neutralization by Immune Passage-A Serum -- Summary -- Avian Sarcoma and Leukosis Viruses,and Canine TVT -- Abstract -- 3.1. Rous Sarcoma Virus (RSV) -- Defective RSV and Helper Viruses (1963) -- Focus Assay for RSV -- BH-RSV and Helper Virus.

Identification of Sarcoma (v-src) Gene and Genome Structure of RSV(1970).