Evidence-Based Evolutionary Medicine

A groundbreaking, evidence-based text to the growing field of evolutionary medicine

Evidence-Based Evolutionary Medicine offers a comprehensive review of the burgeoning field of evolutionary medicine and explores vital topics such as evolution, ecology, and aging as they relate to mainstream medicine. The text integrates Darwinian principles and evidence-based medicine in order to offer a clear picture of the underlying principles that reflect how and why organisms have evolved on a cellular level.

The authors?noted authorities in their respective fields?address evolutionary medicine from a developmental cell-molecular perspective. They explore the first principles of physiology that explain the generation of existing tissues, organs, and organ systems. The text offers an understanding of the overall biology as a vertically integrated whole, from unicellular to multicellular organisms. In addition, it addresses clinical diagnostic and therapeutic approaches, both traditional and cell-homeostatic. This groundbreaking text:

? Offers a much-needed, logical, and fundamental approach to biology and medicine
? Provides a clear explanation of complex physiology and pathophysiology
? Integrates topics like evolution, ecology and aging into mainstream medicine, making them more relevant
? Contains the first evidence-based text on evolutionary medicine

Written for medical and graduate students in biology, physiology, anatomy, endocrinology, reproductive biology, medicine, pathology, systems biology, this vital resource offers a unique text of both biology as an integrated whole with universal properties; and of medicine seeing the individual as a whole, not an inventory of parts and diseases.

Preface xiii

1 A Brief History of Evolutionary Thinking 1

Summary 1

Introduction 2

Darwin 3

Darwin’s Theory 6

The Modern Synthesis 7

The Darkest Chapter 9

Conclusions 14

References 14

2 Outlining the Major Transitions in the History of Life 17

Summary 17

Introduction 18

The Major Transitions 20

Conclusions 29

References 30

3 One Central Mystery: Why Did Eukaryotes Only Evolve Once? 31

Summary 31

Introduction 32

Conclusions 45

References 45

4 A Levels‐of‐Selection View of Evolutionary Physiology 49

Summary 49

Conclusions 59

References 59

5 The Cell as the Smallest Functional Unit of Biology/Physiology 63

Summary 63

In the Beginning 64

The Advent of Multicellularity 65

Evolution: Cellular Style 69

The Water–Land Transition and Vertebrate Evolution 70

The Cellular Approach to Evolution Is Predictive 74

We Are Not Just in This Environment, We Are of It 77

Bioethics Based on Evolutionary Ontology and Epistemology, Not Descriptive Phenotypes, and Genes 78

The Theory of Everything (TOE) 79

Coda 81

References 81

6 Development of Tissues and Organs 83

Summary 83

Introduction 83

Lung Alveolar Morphogenesis 85

Parathyroid Hormone‐Related Protein 86

Stretch‐Induced Cell–Cell Interactions 88

References 89

7 When Homeostasis Fails 91

Summary 91

Introduction 91

Peroxisome Proliferator Activated Receptor Gamma as a Connection to the Evolution of the LIF 93

PPARγ, Statins, and TOR as Mechanisms for Homeostasis 93

Homeostatic Control of What? 93

Pleiotropy: The Deus ex Machina (Ghost in the Machine) 95

Rubik’s Cube as a Metaphor for Pleiotropic Evolution 96

The Lung as the Prototypical Pleiotropic Mechanism 99

The Lung as an Interactive Barrier: Homolog of the Plasma Membrane, Skin, and Brain 102

NKX2.1, Thyroid, Pituitary, and Lung Pleiotropy 104

The Phylogeny of the Thyroid 105

An Evolutionary Vertical Integration of the Phylogeny and Ontogeny of the Thyroid 105

A Retrospective Understanding of Evolution 107

Denouement 109

Conclusions 111

References 112

8 Wnt Signaling During Development 113

Summary 113

Introduction 113

Role of Growth Factors in Alveolar Homeostasis 114

The Kidney Glomerulus as a Homolog of the Lung Alveolus 116

Pathologic Consequences of Failed Paracrine Signaling 117

Reference 117

9 Integrated Regulation of Homeostasis – Vascular, Nervous, Endocrine, Neuroendocrine, Autonomic 119

Summary 119

Introduction 119

Water–Land Transition as the Catalyst for Vertebrate Evolution 121

Parathyroid Hormone‐Related Protein Signaling Is Key to Understanding the Evolution of the Lung 121

The Physics of Lung Evolution 122

Functional Homology between Membrane Lipids and Oxygenation 124

Atmospheric Oxygen, Physiologic Stress, Gene Duplication, and Lung Evolution 125

Duplication of the β Adrenergic Receptor and the Glucocorticoid Receptor Genes 127

Evolution of Endothermy/Homeothermy as Evidence for the Effect of Stress on Vertebrate Physiologic Evolution 127

Hibernation as Reverse Evolution 129

Predictive Power of the Cellular–Molecular Approach to Evolution 131

Conclusions 133

References 136

10 Endogenous and Exogenous Mechanisms for Healing 137

Summary 137

Introduction 138

Endogenous Mechanisms for Healing 138

A Fine Homeostatic Balance between the Differentiated Interstitial Fibroblast and the Myofibroblast 138

Universality of Wnt/β‐catenin in Myofibroblast Proliferation and Scarring: DKK, Shh, Alphabet Soup 140

Prostanoids, Homeostasis, and Regeneration 140

PGJ2 141

ApoE4 143

Evolutionary versus Traditional Medicine 144

Exogenous Mechanisms for Healing Using Evolutionary Principles 145

Summary 145

Cholesterol and Homeostasis 145

Pathophysiology of Hypercholesterolemia 145

Statins as Anti‐Inflammatory Agents 146

PPARγ and Homeostasis 146

TOR and Homeostasis 148

References 148

11 Systems Biology as Recapitulation of Ontogeny and Phylogeny 151

Summary 151

Introduction 151

A Paradigm Shift in Evolution 152

Endothermy as “Proof of Principle” for the Evolution of Serial Exaptations 154

Endothermy Defies Physics, Fostering Migration 155

Conclusions 157

References 158

12 Terminal Addition as Physiologic Homeostasis and Regeneration, or Evolutionary Medicine 159

Summary 159

Introduction 160

Conflicting Viewpoints 161

Terminal Addition as a Perpetual Cellular Link with the Environment 163

Terminal Addition as Layered Cell–Cell Signaling 164

Epigenetic Impacts and Terminal Addition 167

Physiologic Stress, Vascular Shear Stress, Radical Oxygen Species, and Mutation within Constraints = The Mechanism of Terminal Addition 168

Homeobox Genes, Colinearity, and Terminal Addition 169

The Alveolar Lipofibroblast as Terminal Addition 170

The Participation of Glomerular Mesangial Cells 170

PTHrP Effects on the Anterior Pituitary, Adrenal Cortex, and Adrenal Medulla 171

Catecholamines, Lung, and Heart Biology 171

Oxytocin, Endothermy, and the Retina 171

Central Nervous System 172

Terminal Addition, “Reverse Evolution,” and Evolutionary Medicine 172

Discussion 173

Terminal Addition: The Fundament of Haeckel’s Biogenetic Law 173

Somewhere between Gene and Phenotype Lies the Process of Evolution 174

Conclusions 178

References 179

13 Phantom Limbs: Imagination and Epigenetics 181

Summary 181

Introduction 181

Background to Phantom Limb Sensation 182

Relevance of Phantom Limb Sensation to Terminal Addition 183

Phantom Limb Sensation as Non‐Localization 183

Limbs and Hearts 184

Relationship of Limbs to Bipedalism and the Evolution of Birds and Mammals 185

Of Limbs and Consciousness 186

Life as Fractals 186

Consciousness, the Epitome of the Continuum from Inanimate to Animate 188

References 188

14 Man’s Place in the Universe 191

Summary 191

Introduction 192

Anthropomorphisms Subvert the Biologic Imperative to Cooperate 193

Euphysiology 193

References 200

15 Evolution, Deception, and Public Health 203

Summary 203

Part I. Deception Is Deceiving: The Exception that Proves the Rule 203

Introduction 204

In the Beginning 204

Epigenetics and Niche Construction 205

The Deception Proves the Rule 205

Our Own Personal Heliocentrism 206

Deception and Social Pathology 207

Physiologic Stress 208

Ambiguities in Biology 211

Part II. Resolution of the Ambiguities by Assimilating the Deception 214

Introduction 214

The Cell as the First Niche Construction – Self‐Organization Overcomes the Ambiguity 214

The Evolution of Endothermy as Internal Niche Construction; or, Self‐Organization Overcomes Biologic Ambiguities 215

Stress‐Induced Evolution of Endothermy by Stepwise Changes in Physiology Predicts Bipedalism, Evolution of the Avian and Hominid Forelimbs, and Higher Consciousness 217

Cold Stress and DRD4–7: Did Risk‐Taking Drive Us Out of Africa? 218

How Androgens Act to Reduce Ambiguities of Life 220

How Art Seemingly Resolves the Deception of Life 221

How Music Resolves the Deception of Life 221

Literature (Deceptively) Resolves the Ambiguities of Life 222

Liturgy Resolves the Ambiguities of Life: Back to the Garden? 222

Part III. Deception and Public Health 222

Cognitive Dissonance: Scientific Principles, Disease, and Health 223

Part IV. Prediction: Bioethics Based on First Principles of Physiology 224

References 226

Index 227 

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.