Understanding, Prevention and Control of Human Cancer

Robert G. McKinnell, Ph.D. (1959), is a Morse/Alumni Professor Emeritus at the University of Minnesota. He has published scientific studies on animal cloning and herpesvirus cancer. He was a Royal Society of London Guest Research Fellow at the University of Oxford and he was awarded the Prince Hitachi Prize for basic cancer research by the Japanese Cancer Institute, Tokyo.

• Acknowledgements xiAlso by Robert G. McKinnell xivIn Appreciation xvList of Figures xvi1. Cancer is the Most Important Disease of the 21st Century: A Reality Most Fail to Comprehend 1That Reality is Why I Wrote This Book 1Person Years of Life Lost 1New Cases and Deaths 3Chemical Carcinogenesis 3Elizabeth C. and James A. Miller 5A Lack of Recognition 7Who Does Cancer Research? 9Glazed Eyes Not Permitted 102. Cancer for Novices: An Introduction 12Cancer Defined Sans Torture 12The Antiquity of Malignancy 14Metastasis 17Chemotherapy 19Radiation, Viruses, Bacteria, Heredity and/or Possibly “Bad Luck” 20Factors that Give Rise to Cancer: Environment 23Animal Experimentation 31Chemical Structure of Carcinogens 35Carcinogenesis is a Multistep Process 37Concluding Remarks 393. The Millers and Chemical Carcinogenesis 41Carcinogens and Metabolism 41Occam’s (Ockham) Sharp Razor 46Cancer-Causing Dyes 48Can Chemical Structure Predict Carcinogenicity? 55Metabolic Studies of Other Chemicals 56A Synopsis of Metabolic Activation 59The Essential Material of Chemical Carcinogenesis 60Metabolic Activation Requires Enzymes—What Enzymes? 61The Paradox of Cancer-Causing Enzymes in Normal Humans 64Direct Acting Chemical Carcinogens 67Proto-Oncogenes and Tumor Suppressor Genes 68The Significance of the Millers’ Research 69The Quest Continues 704. Serendipity: How the Millers Unintentionally Revolutionized Biology 71A Note about Basic Research 71Test Systems for Mutagens and Carcinogens 73Person to Person Differences in Sensitivity to Environmental Carcinogens 78Molecular Epidemiology: Formation of Macromolecular Adducts as Indicators of Cancer Risk 81Laws Regulating Carcinogens 82Teratogenesis and Drug Metabolism are Related to Metabolic Activation 835. The Family Origins of Elizabeth Cavert Miller: New York, Ireland and Scotland 85Charlton, New York 86An Early Cavert 87Elizabeth’s Heritage Includes a Castle in Scotland 89Elizabeth Cavert’s Father 91Elizabeth Cavert’s Mother 976 More about Elizabeth 99Elizabeth as a Child Lived in Saint Paul, Minnesota 99Elizabeth’s Siblings 100Early Years 104Anoka, Minnesota 105Summers at Fort Plain, New York 109Winters in Anoka, Minnesota 110Springfield, South Dakota 111Elizabeth Cavert’s Father Taught His Children about Agriculture 112Return to Saint Paul and the University of Minnesota 113Two of Elizabeth’s Professors 115Elizabeth as an Undergraduate in 1937 117Graduate School, Biochemistry and Home Economics 1197. James Alexander Miller—How He Became the Other Strand of the Miller Double Helix 123James’ Birth and Growing Up 124University of Pittsburgh 128James A. Miller at the University of Wisconsin-Madison 130Carl August Baumann: Chemist, Hero and Major Professor 132James Meets Elizabeth 135The Wedding 137They Became Like the Two Strands of DNA 137James’ Ph.D. Research 139Elizabeth’s Ph.D. Research 140James and Elizabeth at the McArdle 1438. Elizabeth and James, Beyond the Lab 146Like the Two Strands of DNA—But with Differences 146“They Seemed Normal to Us” 146Elizabeth and James’ Daughters 148Elizabeth Cavert Miller as “Mom” 149The Millers at Home 150The Millers Away from Home 155Was Elizabeth a Feminist? 157James A. Miller from His Daughters’ View 159Family Gatherings in Madison 161Trips to Minnesota 161Trips to Other Places 163Higher Education for Linda and Helen 166An Observant Grandmother 167Elizabeth’s Terminal Illness 167Barbara Butler Miller 168Jim’s Last Illnesses 172Appendices: 1. Awards, Honors and Professional Activities: Elizabeth Cavert Miller (ECM) and James Alexander Miller (JAM), Individually or Jointly 1752. Scientific Publications of Elizabeth Cavert Miller and James Alexander Miller 1793. A Gallery of Cancer Research Covers 1804. Substances Listed in the Thirteenth Report on Carcinogens 186Index 193

"A seminal paper authored in 1947 by Elizabeth C. Miller (1920–87) and James A. Miller (1915–2000) provided the first clue to an underlying common mechanism for the biological activities of chemical carcinogens. […] Robert G. McKinnell has recently published an excellent biography of James and Elizabeth Miller, motivated in part by his desire ‘that the Millers should be recognized by the myriads of ordinary people whose lives have been impacted for the better.’" - Norman Drinkwater, University of Wisconsin-Madison, in: Medical History 61.1 (January 2017)