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Book Details
Abstract
Tony Seed, Gilbert Thompson, Jackie Downs and John MacDermot at the book's launch in LondonThis book brings together in one volume fifteen Nobel Prize-winning discoveries that have had the greatest impact upon medical science and the practice of medicine during the 20th century and up to the present time. Its overall aim is to enlighten, entertain and stimulate. This is especially so for those who are involved in or contemplating a career in medical research.Anyone interested in the particulars of a specific award or Laureate can obtain detailed information on the topic by accessing the Nobel Foundation's website. In contrast, this book aims to provide a less formal and more personal view of the science and scientists involved, by having prominent academics write a chapter each about a Nobel Prize-winning discovery in their own areas of interest and expertise.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| CONTENTS | v | ||
| Foreword by Sir Keith Peters | vii | ||
| Preface by Gilbert Thompson | ix | ||
| Acknowledgements | xiii | ||
| Contributors | xv | ||
| Chapter 1 The Discovery of Insulin Robert Tattersall | 1 | ||
| 1.1 Introduction | 1 | ||
| 1.2 The Pancreas and Diabetes | 1 | ||
| 1.3 Banting and Macleod9 | 4 | ||
| 1.4 The First Clinical Test | 10 | ||
| 1.5 The Nobel Prize | 13 | ||
| 1.6 The Long-term Impact of the Discovery | 15 | ||
| References | 18 | ||
| Chapter 2 The Discovery of the Cure for Pernicious Anaemia, Vitamin B12 A. Victor Hoffbrand | 21 | ||
| 2.1 Introduction | 21 | ||
| 2.2 Brief Biographies | 22 | ||
| 2.2.1 George Whipple | 22 | ||
| 2.2.2 George Minot | 23 | ||
| 2.2.3 William Murphy | 23 | ||
| 2.3 The Medical Problem | 24 | ||
| 2.4 Possible Mechanisms | 25 | ||
| 2.4.1 The nutritional deficiency concept | 26 | ||
| 2.4.2 Why liver therapy worked | 28 | ||
| 2.5 Subsequent Research | 29 | ||
| 2.5.1 Isolation of vitamin B12 | 30 | ||
| 2.5.2 Extrinsic and intrinsic factors | 30 | ||
| 2.5.3 Discovery of folic acid | 32 | ||
| 2.5.4 Two vitamins | 34 | ||
| 2.5.5 Vitamin B12/folate interactions | 35 | ||
| 2.5.6 Neurological damage | 37 | ||
| 2.5.7 Systemic effects of vitamin and folate deficiencies | 37 | ||
| 2.6 Impact of the Discovery of Vitamin B12 on Medical Practice | 39 | ||
| References | 40 | ||
| Chapter 3 The Discovery of Penicillin Eric Sidebottom | 45 | ||
| 3.1 Introduction | 45 | ||
| 3.2 Biographical Sketches10 | 48 | ||
| 3.2.1 Alexander Fleming | 48 | ||
| 3.2.1.1 Education and career | 48 | ||
| 3.2.1.2 The antibiotic revolution and the Fleming myth | 49 | ||
| 3.2.1.3 The man and his achievements | 50 | ||
| 3.2.2 Howard Florey | 51 | ||
| 3.2.2.1 Move to England | 51 | ||
| 3.2.2.2 Cambridge and early work on lysozyme | 51 | ||
| 3.2.2.3 Chair of Pathology in Oxford and the development of penicillin | 52 | ||
| 3.2.2.4 Recognition and its rewards | 52 | ||
| 3.2.3 Ernst Chain | 53 | ||
| 3.2.3.1 Move to Britain | 54 | ||
| 3.2.3.2 Moves to and from Rome | 55 | ||
| 3.3 Steps in the Discovery and Development of Penicillin | 56 | ||
| 3.4 The Impact of the Introduction of Penicillin into Clinical Practice | 61 | ||
| 3.5 From Triumph to Tragedy? | 62 | ||
| 3.6 The Creation of the Fleming Myth | 63 | ||
| 3.7 Allocation of Credit Due and Conclusions | 64 | ||
| References | 66 | ||
| Chapter 4 The Introduction of Cardiac Catheterisation Tony Seed | 69 | ||
| 4.1 Prologue | 69 | ||
| 4.2 Introduction | 70 | ||
| 4.3 Biographical Background of the Laureates | 71 | ||
| 4.3.1 Werner Forssmann | 71 | ||
| 4.3.2 André Cournand | 73 | ||
| 4.3.3 Dickinson Richards | 74 | ||
| 4.4 The Problem: Cardiopulmonary Physiology and Clinical Investigation of the Heart 80 Years Ago | 76 | ||
| 4.5 Description of the Research | 78 | ||
| 4.6 Impact of Cardiac Catheterisation on Medical Science | 83 | ||
| Acknowledgements | 84 | ||
| References | 84 | ||
| Chapter 5 The Discovery of the Structure of DNA James Scott and Gilbert Thompson | 89 | ||
| 5.1 Introduction | 89 | ||
| 5.2 Brief Biographies of the Major Protagonists | 90 | ||
| 5.2.1 Francis Crick | 90 | ||
| 5.2.2 James Watson | 91 | ||
| 5.2.3 Maurice Wilkins | 92 | ||
| 5.2.4 Rosalind Franklin | 93 | ||
| 5.3 Early Discoveries that Paved the Way to Unravelling the Structure of DNA | 94 | ||
| 5.4 Complementary Approaches to Analysing the Structure of DNA in the 1950s | 95 | ||
| 5.4.1 Model building at the Cavendish and X-ray diffraction at King’s | 96 | ||
| 5.4.2 The wrong model | 97 | ||
| 5.4.3 The correct model | 98 | ||
| 5.5 Impact of the Discovery of the Structure of DNA on Medical Science | 100 | ||
| 5.5.1 Mendelian genetics | 102 | ||
| 5.5.2 The HapMap Project | 102 | ||
| 5.5.3 Human history | 103 | ||
| 5.5.4 The genomic basis of common diseases and traits | 104 | ||
| 5.5.5 Somatic cell genomics and cancer | 106 | ||
| 5.5.6 Diagnosis and treatment | 106 | ||
| 5.6 The Future | 107 | ||
| References | 109 | ||
| Chapter 6 The Interpretation of the Genetic Code John MacDermot and Ellis Kempner | 113 | ||
| 6.1 Introduction | 113 | ||
| 6.2 The Scientific Revolution in Medicine 1770–1970 | 113 | ||
| 6.3 Discovery of the Genetic Code | 115 | ||
| 6.4 Implications of the Genetic Code for Clinical Medicine | 125 | ||
| References | 129 | ||
| Chapter 7 The Discovery of Neuropeptides and Radioimmunoassay of Peptide Hormones Jaimini Cegla and Stephen Bloom | 133 | ||
| 7.1 Introduction | 133 | ||
| 7.2 Background of the Laureates | 134 | ||
| 7.2.1 Roger Guillemin | 134 | ||
| 7.2.2 Andrew Schally | 135 | ||
| 7.2.3 Rosalyn Yalow | 137 | ||
| 7.3 Discoveries Concerning the Peptide Hormone Production of the Brain | 138 | ||
| 7.3.1 The elusive link between the hypothalamus and pituitary | 138 | ||
| 7.3.2 Identification of the first hypothalamic hormone: Thyrotropin-releasing hormone (TRH) | 139 | ||
| 7.3.3 Luteinizing hormone-releasing hormone (LHRH) | 140 | ||
| 7.3.4 Somatostatin | 141 | ||
| 7.3.5 Endorphins | 142 | ||
| 7.4 The Development of Radioimmunoassays of Peptide Hormones | 142 | ||
| 7.4.1 Challenges of peptide hormone measurement | 142 | ||
| 7.4.2 The basis of radioimmunoassay | 143 | ||
| 7.4.3 The development of radioimmunoassay | 144 | ||
| 7.4.4 Application of radioimmunoassay | 144 | ||
| 7.4.5 Radioimmunoassay and peptides of the brain | 146 | ||
| References | 146 | ||
| Chapter 8 The Development of Computer-Assisted Tomography Adrian M. K. Thomas | 151 | ||
| 8.1 Introduction | 151 | ||
| 8.2 Brief Biographical Sketches of the Laureates | 151 | ||
| 8.2.1 Allan MacLeod Cormack (1924–1998) | 151 | ||
| 8.2.2 Sir Godfrey Newbold Hounsfield FRS (1919–2004) | 153 | ||
| 8.3 The Medical Problem or Scientific Question | 154 | ||
| 8.4 A Description of the Research that was Undertaken to Provide the Solution | 155 | ||
| 8.4.1 Mathematical basis of CT scanning | 156 | ||
| 8.4.2 Roles of EMI and the Department of Health | 159 | ||
| 8.4.3 Neuroradiological applications of CT scanning | 160 | ||
| 8.5 The Nature and Scale of the Impact of these Discoveries on Medical Science | 164 | ||
| References | 168 | ||
| Chapter 9 The Discovery of Prostaglandins Rod Flower | 171 | ||
| 9.1 Introduction | 171 | ||
| 9.2 Lipids: Just Fats? | 172 | ||
| 9.3 Bergström’s Work on Prostaglandin Purification | 174 | ||
| 9.4 Bergström and Samuelsson’s Work on Prostaglandin Biosynthesis | 177 | ||
| 9.5 Samuelsson’s Work on the Role of Oxygen in the Biosynthetic Reaction | 178 | ||
| 9.6 Vane’s Work with Prostaglandins | 179 | ||
| 9.7 The Discovery of ‘RCS’ | 181 | ||
| 9.8 The Aspirin ‘Enigma’ | 184 | ||
| 9.9 The Detection and Isolation of an Intermediate in Prostaglandin Biosynthesis and RCS Characterised | 188 | ||
| 9.10 Impact of these Discoveries on Medical Science | 192 | ||
| References | 193 | ||
| Chapter 10 The Antibody Problem and the Generation of Monoclonal Antibodies Herman Waldmann and Celia P. Milstein | 197 | ||
| 10.1 Introduction | 197 | ||
| 10.2 Biographical Details of the Laureates | 199 | ||
| 10.2.1 Niels Jerne | 199 | ||
| 10.2.2 Georges Köhler | 200 | ||
| 10.2.3 César Milstein | 201 | ||
| 10.3 The Antibody Problem | 202 | ||
| 10.4 Cell Fusion | 205 | ||
| 10.5 Why is the Discovery Important? | 207 | ||
| 10.5.1 The antibody problem | 207 | ||
| 10.5.2 Impact of diagnostics and research tools | 207 | ||
| 10.5.3 Therapeutic antibodies | 208 | ||
| 10.6 Commercialisation of Monoclonal Antibodies | 210 | ||
| 10.7 Translational Research | 210 | ||
| References | 210 | ||
| Chapter 11 The Discovery of the LDL Receptor and Its Role in Cholesterol Metabolism Gilbert Thompson | 217 | ||
| 11.1 Introduction | 217 | ||
| 11.2 Biographical Background of the Laureates | 218 | ||
| 11.2.1 Joseph Goldstein | 218 | ||
| 11.2.2 Michael Brown | 219 | ||
| 11.3 The Problem: Familial Hypercholesterolaemia 40 Years Ago | 220 | ||
| 11.4 The Solution: Discovery of the LDL Receptor and its Partial or Complete Absence in FH | 222 | ||
| 11.5 The Scavenger Receptor and Atherosclerosis | 226 | ||
| 11.6 Stimulation of Receptor-mediated Catabolism of LDL by Statins | 227 | ||
| 11.7 Analysis of the LDL Receptor Gene and Mutations Causing FH | 229 | ||
| 11.8 Impact of these Discoveries on Medical Science | 231 | ||
| References | 231 | ||
| Chapter 12 The Invention of the Polymerase Chain Reaction and Use of Site-Directed Mutagenesis Anne K. Soutar | 237 | ||
| 12.1 Introduction | 237 | ||
| 12.2 Michael Smith (1932–2000) | 238 | ||
| 12.2.1 Biographical sketch: early life and education* | 238 | ||
| 12.2.2 From postdoctoral fellow to independent scientist | 239 | ||
| 12.2.3 Work that led to the Nobel Prize | 241 | ||
| 12.3 Kary Mullis (1944– ) | 247 | ||
| 12.3.1 Biographical sketch: early life and education | 247 | ||
| 12.3.2 Joining the Cetus Corporation: work that led to the Nobel Prize | 249 | ||
| 12.4 How these Nobel Prize-winning Discoveries Changed Medicine | 253 | ||
| 12.4.1 The impact of PCR and site-directed mutagenesis on medical practice | 253 | ||
| 12.4.2 An example of how PCR and site-directed mutagenesis changed research into inherited disease | 256 | ||
| References | 258 | ||
| Chapter 13 The Discovery of the Pathophysiological Role of Nitric Oxide in Blood Vessels Keith M. Channon | 263 | ||
| 13.1 Introduction | 263 | ||
| 13.2 Biographical Backgrounds of the Laureates | 264 | ||
| 13.2.1 Robert Furchgott | 264 | ||
| 13.2.2 Ferid Murad | 266 | ||
| 13.2.3 Louis Ignarro | 267 | ||
| 13.3 Identification of Endothelium-Derived Relaxing Factor | 268 | ||
| 13.4 Physiological Significance of Nitric Oxide | 272 | ||
| 13.5 Therapeutic Consequences of the Discovery of the Role of Nitric Oxide | 274 | ||
| References | 277 | ||
| Chapter 14 The Discovery of Helicobacter Pylori Chris Hawkey | 281 | ||
| 14.1 Synopsis | 281 | ||
| 14.2 Biographies | 282 | ||
| 14.2.1 Robin Warren | 282 | ||
| 14.2.1.1 Family | 282 | ||
| 14.2.1.2 Education | 283 | ||
| 14.2.1.3 Professional and personal life | 283 | ||
| 14.2.1.4 Personality | 283 | ||
| 14.2.2 Barry Marshall | 284 | ||
| 14.2.2.1 Family | 284 | ||
| 14.2.2.2 Education | 284 | ||
| 14.2.2.3 Professional and personal life | 285 | ||
| 14.2.2.4 Personality | 285 | ||
| 14.3 The Medical Problem that was Addressed | 285 | ||
| 14.3.1 Gastric ulcers | 285 | ||
| 14.3.2 Duodenal ulcers | 287 | ||
| 14.3.3 Aspirin | 288 | ||
| 14.3.4 False theories and treatments | 288 | ||
| 14.3.5 H2 antagonists | 289 | ||
| 14.3.6 Bismuth | 290 | ||
| 14.3.7 Gastric bacteria | 290 | ||
| 14.4 The Research | 291 | ||
| 14.4.1 September–December 1981 | 291 | ||
| 14.4.2 1982 | 291 | ||
| 14.4.2.1 First culture | 291 | ||
| 14.4.2.2 Bacteria and ulcers | 292 | ||
| 14.4.2.3 First reactions | 292 | ||
| 14.4.3 1983 | 293 | ||
| 14.4.3.1 First publication | 293 | ||
| 14.4.3.2 Serology and a wild theory | 294 | ||
| 14.4.3.3 Bactericidal bismuth | 294 | ||
| 14.4.4 1984 | 294 | ||
| 14.4.4.1 Self-ingestion | 294 | ||
| 14.4.4.2 Growing interest | 296 | ||
| 14.4.4.3 Urease testing | 297 | ||
| 14.4.5 1985 | 298 | ||
| 14.4.5.1 First randomised controlled trial of antibiotic treatments for ulcers | 298 | ||
| 14.4.5.2 Teamwork | 298 | ||
| 14.4.5.3 Resistance | 299 | ||
| 14.4.5.4 Full circle | 299 | ||
| 14.5 Impact on Medical Science | 300 | ||
| 14.5.1 Peptic ulceration | 300 | ||
| 14.5.2 Dyspepsia management | 301 | ||
| 14.5.3 NSAIDs and aspirin as a cause of ulcers and the development of selective cyclooxygenase (COX)-2 inhibitors | 301 | ||
| 14.5.4 Reflux | 301 | ||
| 14.5.5 Malignancies | 302 | ||
| 14.5.6 Genetic microbiology | 302 | ||
| 14.5.7 Evolution | 302 | ||
| 14.5.8 History of disease | 303 | ||
| 14.5.9 Consequences of H. pylori loss | 303 | ||
| 14.5.10 Save the Helicobacter! | 303 | ||
| References | 304 | ||
| Chapter 15 The Discovery of RNA Interference — Gene Silencing by Double-Stranded RNA Richard P. Hull and Timothy J. Aitman | 309 | ||
| 15.1 Introduction | 309 | ||
| 15.2 Biographical and Scientific Background of the Laureates | 310 | ||
| 15.2.1 Andrew Fire | 310 | ||
| 15.2.2 Craig Mello | 311 | ||
| 15.3 The Discovery of Genetic Interference by Double-Stranded RNA | 313 | ||
| 15.4 Understanding the Mechanism Underlying RNAi | 315 | ||
| 15.5 RNAi Functions in the Cell and Viral Infection | 320 | ||
| 15.6 The Impact of RNA Interference on Biomedical Research and Drug Discovery | 321 | ||
| 15.7 The Potential for RNA Interference as a Novel Therapeutic Modality | 322 | ||
| 15.8 Conclusions | 324 | ||
| Acknowledgements | 325 | ||
| References | 325 | ||
| Appendix: The First 100 Nobel Prizes in Physiology or Medicine | 329 | ||
| Abbreviations used in Table | 333 | ||
| Index | 335 |