Evidence-Based Evolutionary Medicine

About the Authors John S. Torday is a Professor of Pediatrics at UCLA, USA. Neil W. Blackstone is a Professor in the Department of Biological Sciences at Northern Illinois University, USA. Virender K. Rehan is a Professor of Pediatrics at UCLA, USA.

• Preface xiii1 A Brief History of Evolutionary Thinking 1Summary 1Introduction 2Darwin 3Darwin’s Theory 6The Modern Synthesis 7The Darkest Chapter 9Conclusions 14References 142 Outlining the Major Transitions in the History of Life 17Summary 17Introduction 18The Major Transitions 20Conclusions 29References 303 One Central Mystery: Why Did Eukaryotes Only Evolve Once? 31Summary 31Introduction 32Conclusions 45References 454 A Levels‐of‐Selection View of Evolutionary Physiology 49Summary 49Conclusions 59References 595 The Cell as the Smallest Functional Unit of Biology/Physiology 63Summary 63In the Beginning 64The Advent of Multicellularity 65Evolution: Cellular Style 69The Water–Land Transition and Vertebrate Evolution 70The Cellular Approach to Evolution Is Predictive 74We Are Not Just in This Environment, We Are of It 77Bioethics Based on Evolutionary Ontology and Epistemology, Not Descriptive Phenotypes, and Genes 78The Theory of Everything (TOE) 79Coda 81References 816 Development of Tissues and Organs 83Summary 83Introduction 83Lung Alveolar Morphogenesis 85Parathyroid Hormone‐Related Protein 86Stretch‐Induced Cell–Cell Interactions 88References 897 When Homeostasis Fails 91Summary 91Introduction 91Peroxisome Proliferator Activated Receptor Gamma as a Connection to the Evolution of the LIF 93PPARγ, Statins, and TOR as Mechanisms for Homeostasis 93Homeostatic Control of What? 93Pleiotropy: The Deus ex Machina (Ghost in the Machine) 95Rubik’s Cube as a Metaphor for Pleiotropic Evolution 96The Lung as the Prototypical Pleiotropic Mechanism 99The Lung as an Interactive Barrier: Homolog of the Plasma Membrane, Skin, and Brain 102NKX2.1, Thyroid, Pituitary, and Lung Pleiotropy 104The Phylogeny of the Thyroid 105An Evolutionary Vertical Integration of the Phylogeny and Ontogeny of the Thyroid 105A Retrospective Understanding of Evolution 107Denouement 109Conclusions 111References 1128 Wnt Signaling During Development 113Summary 113Introduction 113Role of Growth Factors in Alveolar Homeostasis 114The Kidney Glomerulus as a Homolog of the Lung Alveolus 116Pathologic Consequences of Failed Paracrine Signaling 117Reference 1179 Integrated Regulation of Homeostasis – Vascular, Nervous, Endocrine, Neuroendocrine, Autonomic 119Summary 119Introduction 119Water–Land Transition as the Catalyst for Vertebrate Evolution 121Parathyroid Hormone‐Related Protein Signaling Is Key to Understanding the Evolution of the Lung 121The Physics of Lung Evolution 122Functional Homology between Membrane Lipids and Oxygenation 124Atmospheric Oxygen, Physiologic Stress, Gene Duplication, and Lung Evolution 125Duplication of the β Adrenergic Receptor and the Glucocorticoid Receptor Genes 127Evolution of Endothermy/Homeothermy as Evidence for the Effect of Stress on Vertebrate Physiologic Evolution 127Hibernation as Reverse Evolution 129Predictive Power of the Cellular–Molecular Approach to Evolution 131Conclusions 133References 13610 Endogenous and Exogenous Mechanisms for Healing 137Summary 137Introduction 138Endogenous Mechanisms for Healing 138A Fine Homeostatic Balance between the Differentiated Interstitial Fibroblast and the Myofibroblast 138Universality of Wnt/β‐catenin in Myofibroblast Proliferation and Scarring: DKK, Shh, Alphabet Soup 140Prostanoids, Homeostasis, and Regeneration 140PGJ2 141ApoE4 143Evolutionary versus Traditional Medicine 144Exogenous Mechanisms for Healing Using Evolutionary Principles 145Summary 145Cholesterol and Homeostasis 145Pathophysiology of Hypercholesterolemia 145Statins as Anti‐Inflammatory Agents 146PPARγ and Homeostasis 146TOR and Homeostasis 148References 14811 Systems Biology as Recapitulation of Ontogeny and Phylogeny 151Summary 151Introduction 151A Paradigm Shift in Evolution 152Endothermy as “Proof of Principle” for the Evolution of Serial Exaptations 154Endothermy Defies Physics, Fostering Migration 155Conclusions 157References 15812 Terminal Addition as Physiologic Homeostasis and Regeneration, or Evolutionary Medicine 159Summary 159Introduction 160Conflicting Viewpoints 161Terminal Addition as a Perpetual Cellular Link with the Environment 163Terminal Addition as Layered Cell–Cell Signaling 164Epigenetic Impacts and Terminal Addition 167Physiologic Stress, Vascular Shear Stress, Radical Oxygen Species, and Mutation within Constraints = The Mechanism of Terminal Addition 168Homeobox Genes, Colinearity, and Terminal Addition 169The Alveolar Lipofibroblast as Terminal Addition 170The Participation of Glomerular Mesangial Cells 170PTHrP Effects on the Anterior Pituitary, Adrenal Cortex, and Adrenal Medulla 171Catecholamines, Lung, and Heart Biology 171Oxytocin, Endothermy, and the Retina 171Central Nervous System 172Terminal Addition, “Reverse Evolution,” and Evolutionary Medicine 172Discussion 173Terminal Addition: The Fundament of Haeckel’s Biogenetic Law 173Somewhere between Gene and Phenotype Lies the Process of Evolution 174Conclusions 178References 17913 Phantom Limbs: Imagination and Epigenetics 181Summary 181Introduction 181Background to Phantom Limb Sensation 182Relevance of Phantom Limb Sensation to Terminal Addition 183Phantom Limb Sensation as Non‐Localization 183Limbs and Hearts 184Relationship of Limbs to Bipedalism and the Evolution of Birds and Mammals 185Of Limbs and Consciousness 186Life as Fractals 186Consciousness, the Epitome of the Continuum from Inanimate to Animate 188References 18814 Man’s Place in the Universe 191Summary 191Introduction 192Anthropomorphisms Subvert the Biologic Imperative to Cooperate 193Euphysiology 193References 20015 Evolution, Deception, and Public Health 203Summary 203Part I. Deception Is Deceiving: The Exception that Proves the Rule 203Introduction 204In the Beginning 204Epigenetics and Niche Construction 205The Deception Proves the Rule 205Our Own Personal Heliocentrism 206Deception and Social Pathology 207Physiologic Stress 208Ambiguities in Biology 211Part II. Resolution of the Ambiguities by Assimilating the Deception 214Introduction 214The Cell as the First Niche Construction – Self‐Organization Overcomes the Ambiguity 214The Evolution of Endothermy as Internal Niche Construction; or, Self‐Organization Overcomes Biologic Ambiguities 215Stress‐Induced Evolution of Endothermy by Stepwise Changes in Physiology Predicts Bipedalism, Evolution of the Avian and Hominid Forelimbs, and Higher Consciousness 217Cold Stress and DRD4–7: Did Risk‐Taking Drive Us Out of Africa? 218How Androgens Act to Reduce Ambiguities of Life 220How Art Seemingly Resolves the Deception of Life 221How Music Resolves the Deception of Life 221Literature (Deceptively) Resolves the Ambiguities of Life 222Liturgy Resolves the Ambiguities of Life: Back to the Garden? 222Part III. Deception and Public Health 222Cognitive Dissonance: Scientific Principles, Disease, and Health 223Part IV. Prediction: Bioethics Based on First Principles of Physiology 224References 226Index 227