Front Cover -- Systems Biology -- Copyright Page -- Table of Contents -- List of Contributors -- Contributor Biographies -- Preface -- SECTION I Introduction -- Chapter 1 Towards philosophical foundations of Systems Biology: introduction -- 1. SYSTEMS BIOLOGY: A NEW SCIENCE IN SEARCH OF METHODOLOGIES AND PHILOSOPHICAL FOUNDATIONS -- 2. SYSTEMS BIOLOGY -- 2.1. History of systems biology -- 2.2. What is contemporary systems biology? -- 2.3. Approaches to systems biology -- 3. TOWARDS A PHILOSOPHY OF SYSTEMS BIOLOGY -- 3.1. The philosophy of molecular biology itself needs no further elaboration -- 3.2. Philosophers focus on philosophy of evolutionary biology -- 3.3. A philosophy of systems biology is lacking but needed -- 4. INTRODUCTION OF A NUMBER OF PHILOSOPHICAL ASPECTS OF SYSTEMS BIOLOGY -- 4.1. Two types of reductionism -- 4.2. A continuum of reductionism to antireductionism -- 4.3. Types of explanation -- 4.4. Mechanistic explanation -- 4.5. Systems biology and models -- 4.6. What is life? -- 5. AIM AND OVERVIEW OF THE BOOK -- REFERENCES -- SECTION II Research programs of Systems Biology -- Chapter 2 The methodologies of systems biology -- SUMMARY -- 1. THE METHODOLOGY AND PHILOSOPHICAL FOUNDATIONS OF THE VARIOUS SCIENCES -- 1.1. Physics -- 1.2. Biology -- 1.3. Biochemistry and molecular biology -- 1.4. Cell Biology: The living cell -- 2. LIMITATIONS TO THE SCIENTIFIC STATUS OF BIOCHEMISTRY AND MOLECULAR BIOLOGY -- 2.1. Inaccuracy -- 2.2. Inability to deal with emergence -- 2.3. Frustrated aspiration of biochemistry and molecular biology to . . . biology -- 2.4. Irreducibility -- 2.5. Lack of testability because of undefinedness -- 2.6. Lack of experimental accessibility -- 2.7. Lack of analysability -- 3. RISING ABOVE THE LIMITATIONS -- 3.1. Genomics -- 3.2. Soon everything will be known . . . : Will biology become physics, at last?.

3.3. Observing or understanding? -- 3.4. Systems biology -- 4. TOWARDS A SYSTEMATIC METHODOLOGY OF SYSTEMS BIOLOGY -- 4.1. The goals of systems biology -- 4.2. Systems biology: What it is -- 4.3. The spiral of knowledge -- 4.4. The special role of mathematics in systems biology: Calculating emergence -- ACKNOWLEDGEMENTS -- REFERENCES -- Chapter 3 Methodology is Philosophy -- SUMMARY -- 1. INTRODUCTION -- 2. FROM MOLECULES TO DIABETES VIA METABOLISM AND SYSTEMIC PHYSIOLOGY -- 3. MRS AND MCA FORM A SUCCESSFUL METHODOLOGY FOR SYSTEMS BIOLOGY -- 4. CONCLUSION -- REFERENCES -- Chapter 4 How can we understand metabolism? -- SUMMARY -- 1. INTRODUCTION -- 2. TRADITIONAL PRINCIPLES OF METABOLISM -- 3. THE RISE OF SYSTEMS ANALYSIS OF METABOLISM -- 4. SHOULD WE EXPECT METABOLISM TO BE UNDERSTANDABLE? -- 5. IS SIMULATING CELL METABOLISM THE SAME AS UNDERSTANDING IT? -- REFERENCES -- Chapter 5 On building reliable pictures with unreliable data: An evolutionary and developmental coda for the new systems biology? -- SUMMARY -- 1. INTRODUCTION -- 2. THE NEW SYSTEMS BIOLOGY AND EVO-DEVO -- 3. THE PROBLEM OF DATA RELIABILITY IN THE ANALYSIS OF LARGE SYSTEMS -- 4. DATA ERRORS AND MOLAR SYSTEM PROPERTIES -- 5. ROBUSTNESS AND THE MANAGEMENT OF UNCERTAINTY -- 6. GENERATIVE ENTRENCHMENT -- REFERENCES -- SECTION III Theory and models -- Chapter 6 Mechanism and mechanical explanation in systems biology -- SUMMARY -- 1. INTRODUCTION: MECHANISTIC EXPLANATION AND REDUCTION -- 2. LEVELS OF ORGANIZATION AND DEGREES OF RESOLUTION -- 3. THE DEVELOPMENT OF THE LAC OPERON AS A MECHANISTIC MODEL -- 4. MECHANISM AND EMERGENCE -- 5. CONCLUSION: MECHANISTIC EXPLANATION AND SYSTEMS BIOLOGY -- REFERENCES -- Chapter 7 Theories, models, and equations in systems biology -- SUMMARY -- 1. INTRODUCTION: THE STRUCTURE OF BIOLOGICAL THEORIES.

2. THE DEVELOPMENT OF THE HODGKIN-HUXLEY GIANT SQUID MODEL FOR ACTION POTENTIALS AS A CLASSICAL EXAMPLE OF SYSTEMS BIOLOGY -- 3. IMPLICATIONS OF THE HODGKIN-HUXLEY MODEL AND THEIR METHODOLOGY -- 3.1. One basic mechanism with many types of molecular realizations? -- 3.2. Genetic and epigenetic diversity accounts for ion channel diversity -- 3.3. The H and H 'basic mechanism' as an emergent simplification -- 4. A NEUROSCIENTIFIC ACCOUNT OF BEHAVIOR IN C. ELEGANS -- 5. IMPLICATIONS OF THE FERRÉE AND LOCKERY MODEL FOR C. ELEGANS CHEMOTAXIS -- 6. EIGHT IMPLICATIONS OF THE TWO EXEMPLARS FOR SYSTEMS BIOLOGY -- REFERENCES -- Chapter 8 All models are wrong . . . some more than others -- SUMMARY -- 1. INTRODUCTION -- 2. MODELLING THE MODELLING PROCESS -- 3. ANALYTICAL MODELLING -- 4. SYNTHETIC MODELLING -- 5. SYNTHETIC VS. ANALYTIC MODELLING -- 6. DYNAMIC PATHWAY MODELLING -- 7. ALL MODELS ARE WRONG, SOME ARE USEFUL -- ACKNOWLEDGEMENTS -- REFERENCES -- Chapter 9 Data without models merging with models without data -- SUMMARY -- 1. INTRODUCTION -- 2. PRELIMINARY TOPOGRAPHY OF THE FIELD -- 3. THE FIRST ROOT OF SYSTEMS BIOLOGY: MODELS OF METABOLIC AND SIGNALING PATHWAYS -- 3.1. Regulatory metabolic and signaling systems -- 3.2. Modeling regulatory networks and gathering data -- 4. THE SECOND ROOT OF SYSTEMS BIOLOGY: BIOLOGICAL CYBERNETICS AND MATHEMATICAL SYSTEMS ANALYSIS -- 4.1. Cybernetic models in biology -- 4.2. Contents of the black boxes and the 'direction' of cybernetic modeling -- 5. THE THIRD ROOT OF SYSTEMS BIOLOGY: 'OMICS' -- 5.1. Early genome projects: Chromosome maps -- 5.2. Molecular genome projects -- 5.3. Early proteomic projects -- 6. THE BRANCHES OF SYSTEMS BIOLOGY: MERGERS OF THE DIFFERENT ROOTS -- 6.1. The first branch of systems biology: Detailed bottom-up regulatory models.

6.2. The second branch of systems biology: Making sense of 'omic' data by top-down modeling -- 7. THE STRUCTURE OF THE FIELD -- 8. EPISTEMOLOGICAL AND ONTOLOGICAL ISSUES REGARDING TOP-DOWN SYSTEMS BIOLOGY -- 8.1. Decomposition of large networks and functionality -- 8.2. The 'holism' of systems biology -- 8.3. 'Realistic' representation and systems biological 'models of everything' -- 9. CONCLUSION -- REFERENCES -- SECTION IV Organization in biological systems -- Chapter 10 The biochemical factory that autonomously fabricates itself: A systems biological view of the living cell -- SUMMARY -- 1. HOW TO BE A SYSTEMS BIOLOGIST -- 2. THE SELF-FABRICATING CELL: A CONTEXT FOR SYSTEMS BIOLOGY -- 3. AUTONOMY OF MATERIAL SYSTEMS: THE NEED FOR SPECIFIC CATALYSIS -- 4. FABRICATION AND THE LOGIC OF LIFE -- 5. HOW TO CONSTRUCT A SELF-FABRICATING FACTORY -- 6. SELF-FABRICATION IN LIVING SYSTEMS -- 7. CONCLUSION -- ACKNOWLEDGEMENTS -- REFERENCES -- Chapter 11 A systemic approach to the origin of biological organization -- SUMMARY -- 1. INTRODUCTION -- 2. THE ORGANIZATIONAL PERSPECTIVE -- 3. THE STARTING POINT: NONTRIVIAL SELF-MAINTENANCE -- 3.1. From self-organization to NTSM -- 3.2. The problem of the origin of NTSMSs -- 4. NTSM ORGANIZATION AND AUTONOMY -- 5. THE EMERGENCE OF A HISTORICAL-COLLECTIVE DIMENSION -- 5.1. Autonomous systems with memory -- 5.2. The origin of an informational organization -- 6. THE OPEN STRUCTURE OF DARWINIAN EVOLUTION -- 7. CONCLUDING REMARKS -- ACKNOWLEDGMENTS -- REFERENCES -- Chapter 12 Biological mechanisms: organized to maintain autonomy -- SUMMARY -- 1. INTRODUCTION -- 2. THE BASIC CONCEPTION OF MECHANISM -- 3. THE VITALIST CHALLENGE -- 4. FIRST STEPS: BERNARD, CANNON, AND CYBERNETICS -- 5. CYCLIC ORGANIZATION AND GÁNTI'S CHEMOTON -- 6. FROM GÁNTI'S CHEMOTON TO AUTONOMOUS SYSTEMS -- 7. CONCLUDING THOUGHTS: BEYOND BASIC AUTONOMY.

REFERENCES -- Chapter 13 The disappearance of function from 'self-organizing systems' -- SUMMARY -- REFERENCES -- SECTION V Conclusion -- Chapter 14 Afterthoughts as foundations for systems biology -- 1. SYSTEMS BIOLOGY IS FUNCTIONAL AND MECHANISTIC RATHER THAN EVOLUTIONARY BIOLOGY -- 2. SYSTEMS BIOLOGICAL EXPLANATIONS ARE OFTEN MECHANISTIC EXPLANATIONS -- 3. OTHER TYPES OF EXPLANATION ARE ALSO IMPORTANT FOR SYSTEMS BIOLOGY -- 4. DESCRIPTION OF MOLECULAR MECHANISMS USING MODELS -- 5. MODELS AND THE NONEQUILIBRIUM ORGANIZATION OF LIVING SYSTEMS -- 6. EMERGENT PROPERTIES -- 7. THEORIES AND LAWS IN SYSTEMS BIOLOGY -- 8. EXPLANATORY PLURALISM: INTRALEVEL AND INTERLEVEL THEORIES -- 9. WHAT IS LIFE? -- 10. CONCLUDING REMARKS -- REFERENCES -- Subject Index.