John Torday, PhD, is Professor of Pediatrics and Ob/Gyn at Harbor-UCLA Medical Center where he is also Director of The Henry L. Guenther Laboratory for Cell/Molecular Research and Director of Laboratory for Evolutionary Preventive Medicine.  He is the author of over 130 peer-reviewed articles, Dr. Torday specializes in pre and neo-natal lung development, particularly regarding cell-cell communication within this pathway. V.K. Rehan, MD, is Professor of Pediatrics and Director of the Neonatal Intensive Care Unit at Harbor-UCLA Medical Center.  The recipient of numerous teaching honors, Dr. Rehan is involved both in treating patients and continuing research on neo and peri-natal respiratory issues and lung development.

"…the book offers the biology-savvy reader with interesting insights into the contribution of cell-cell interactions to the development and evolution of phenotypes.  Given the technical nature of the subject, this book will have particular appeal among researchers and students of cellular and molecular biology and among evolutionary biologists interested in the pathways linking genes to phenotypes.  In keeping with the complexity of the topic, there is much to digest here, and readers knowledgeable in these fields will find interesting food for thought.”  (Quarterly Reviews in Biology, 1  July 2013)

• Preface xi About the Authors xiii1 THE CELLULAR ORIGIN OF VERTEBRATES 1The Origins of Unicellular Life on Earth 1Prokaryotes versus Eukaryotes 4Coevolution of traits 5Cholesterol Facilitates Lipid Rafts for Cell–Cell Communication 7The Endomembrane System 9The Cellular Mechanism of Evolution 10Why Evolve? 11Cell–Cell Communication and Aging 122 REDUCING LUNG PHYSIOLOGY TO ITS MOLECULAR PHENOTYPES 17Hormonal Acceleration of Lung Development 17Neutral Lipid Traffi cking and Lung Evolution 19Other Examples of Cellular Cooperativity 23Summary 243 A CELL–MOLECULAR STRATEGY FOR SOLVING THE EVOLUTIONARY PUZZLE 25Rationale for Cell–Molecular Evolution 25Mechanism of Mammalian Lung Development 28Avian Lung Structure–Function Relationship: The Exception that Proves the Rule 32Does Ontogeny Recapitulate Phylogeny? The Role of PTHrP in Lung Development 32Interrelationship between PTHrP, Development, Physiology, and Repair: Is Repair a Recapitulation of Ontogeny and Phylogeny? 334 THE EVOLUTION OF CELL–CELL COMMUNICATION 35Cell–Cell Communication as the Mechanistic Basis for Evolutionary Biology 36The Darwinian Biologic Spacetime Continuum and Einstein’s Vision of the Universe 37Reverse Engineering of Physiologic Traits as a Portal for Viewing Evolution 38Cell–Cell Communication as the Basis for the Evolution of Metazoans 41Understanding Lung Evolution from the Middle Out 42The Cell–Cell Communication Model of Lung Evolution Traces Contemporary Phenotypes Back to Ancestral Phenotypes 43Predictive Value of the Lung Cell–Cell Communication Model for Understanding the Evolution of Physiologic Systems 44Sexual Dimorphism of Lung Development: A Case Study in Cell–Cell Communication and Evolutionary Plasticity 46Androgen Affects the Expression of Growth Factors Involved in Lung Development 48Evidence for an Association between Steroid-Resistant/Responsive Phenotypes and Human Lymphocyte Antigen (HLA) Haplotypes 495 HOW TO INTEGRATE CELL-MOLECULAR DEVELOPMENT, HOMEOSTASIS, ECOLOGY, AND EVOLUTIONARY BIOLOGY: THE MISSING LINKS 53Neutral Theory versus Intelligent Design 54Internal Selection Theory 54The Counterintuitive Nature of Physiology and Solution to the Dead Sea Scrolls Puzzle 57The Continuum from Microevolution to Macroevolution 58cis Regulation and Adaptive Evolution 69Evolution of cis Regulatory Mechanisms 706 FROM CELL–CELL COMMUNICATION TO THE EVOLUTION OF INTEGRATED PHYSIOLOGY 75Cell–cell Signaling and Alveolar Development: A Reductionist Approach to the Evolution of Physiologic Traits 77An Integrated, Empiric, Middle–Out Approach to Physiology 79A Molecular Evolutionary Link between the Lung and the Kidney? 82The Berner Hypothesis and Emergence of the Adipocyte: The Evolutionary Origins of the Lipofi broblast 83Lung Biology as a Cipher for Evolution 85Do Stretch Effects on PTHrP Expression Reflect Its Role in Adapting to Gravity? 85Wolff’s Law Works for Both Bone and Lung 88Functional Relationship between the External and Internal Environments 89An Evolutionary Vertical Integration of the Phylogeny and Ontogeny of the Thyroid 917 EXPLOITING CELL–CELL COMMUNICATION ACROSS SPACETIME TO DECONSTRUCT EVOLUTION 95Somewhere between the Gene and the Phenotype Lies the Process of Evolution 98A Functional Genomic Approach to Evolution as an Example of Terminal Addition 100Seeking Deep Homologies in Lung Evolution 102Systems Biology Based on Cell–Cell Communication 105Vertical Integration of Leptin Signaling, Human Evolution, and the Trojan Horse Effect 108Leptin and Human Evolution: Food for Thought 1098 THE PERIODIC TABLE OF BIOLOGY 115The Prospect of a Periodic Table of Biology 115Cellular Cooperation Is Key 116Elemental Biology 118PTHrP as an Archetype 118Evolution as the Solution 119Ramping Up a Mathematical Model of Evolution 121The Anthropic Principle Results from the Evolution of Cell–Cell Interactions 1249 VALUE ADDED BY THINKING IN TERMS OF THE CELL–CELL COMMUNICATION MODEL FOR EVOLUTION 125This is Not a Just-So Story 126Beyond Genomics 128From Fat Cells to Integrated Physiology 128Molecular Homologies Distinguish between the Evolutionary Forest and Trees 129The Oxygen–Cholesterol–Surfactant–Membrane Connection 130Cholesterol Metabolism as the Data Operating System for Vertebrate Biology? 131Translation of Genomics into the Periodic Table for Biology 132Deep Homologies 134Selection Pressure for Cell–Cell Communication: The Key to Understanding Evolution 13510 CELL–CELL COMMUNICATION AS THE BASIS FOR PRACTICING CLINICAL MEDICINE 139Cell–Cell Communication Maintenance and Breakdown Represent Heath and Disease, Respectively 140Cell–Cell Communications as a Framework for Human Evolution 140Canalization, Decanalization, and the Holistic Approach to the Practice of Medicine 141Exploiting Lung Evolution to Prevent and Treat Chronic Lung Disease 141Lung Evolution Explains the Magic of Continuous Positive Airway Pressure 142The Paradox of Infecting the Lung in Order to Treat Lung Disease Caused by Infection 143Exploiting Lung Evolution to Prevent and Treat Smoking-Related Lung Damage 144The Trojan Horse Effect of Canalization 145Impetus for Evolutionary Science as an Integral Part of the Clinical Curriculum 146Application of Evolutionary Science to Bioethics 147Evolutionary Science, a Biologic Periodic Table, and a Unifi ed Theory of Biology 148Summary 149Name Index 151Subject Index 153

John Torday, PhD, is Professor of Pediatrics and Ob/Gyn at Harbor-UCLA Medical Center where he is also Director of The Henry L. Guenther Laboratory for Cell/Molecular Research and Director of Laboratory for Evolutionary Preventive Medicine.  He is the author of over 130 peer-reviewed articles, Dr. Torday specializes in pre and neo-natal lung development, particularly regarding cell-cell communication within this pathway. V.K. Rehan, MD, is Professor of Pediatrics and Director of the Neonatal Intensive Care Unit at Harbor-UCLA Medical Center.  The recipient of numerous teaching honors, Dr. Rehan is involved both in treating patients and continuing research on neo and peri-natal respiratory issues and lung development.

"…the book offers the biology-savvy reader with interesting insights into the contribution of cell-cell interactions to the development and evolution of phenotypes.  Given the technical nature of the subject, this book will have particular appeal among researchers and students of cellular and molecular biology and among evolutionary biologists interested in the pathways linking genes to phenotypes.  In keeping with the complexity of the topic, there is much to digest here, and readers knowledgeable in these fields will find interesting food for thought.”  (Quarterly Reviews in Biology, 1  July 2013)

• Preface xi About the Authors xiii1 THE CELLULAR ORIGIN OF VERTEBRATES 1The Origins of Unicellular Life on Earth 1Prokaryotes versus Eukaryotes 4Coevolution of traits 5Cholesterol Facilitates Lipid Rafts for Cell–Cell Communication 7The Endomembrane System 9The Cellular Mechanism of Evolution 10Why Evolve? 11Cell–Cell Communication and Aging 122 REDUCING LUNG PHYSIOLOGY TO ITS MOLECULAR PHENOTYPES 17Hormonal Acceleration of Lung Development 17Neutral Lipid Traffi cking and Lung Evolution 19Other Examples of Cellular Cooperativity 23Summary 243 A CELL–MOLECULAR STRATEGY FOR SOLVING THE EVOLUTIONARY PUZZLE 25Rationale for Cell–Molecular Evolution 25Mechanism of Mammalian Lung Development 28Avian Lung Structure–Function Relationship: The Exception that Proves the Rule 32Does Ontogeny Recapitulate Phylogeny? The Role of PTHrP in Lung Development 32Interrelationship between PTHrP, Development, Physiology, and Repair: Is Repair a Recapitulation of Ontogeny and Phylogeny? 334 THE EVOLUTION OF CELL–CELL COMMUNICATION 35Cell–Cell Communication as the Mechanistic Basis for Evolutionary Biology 36The Darwinian Biologic Spacetime Continuum and Einstein’s Vision of the Universe 37Reverse Engineering of Physiologic Traits as a Portal for Viewing Evolution 38Cell–Cell Communication as the Basis for the Evolution of Metazoans 41Understanding Lung Evolution from the Middle Out 42The Cell–Cell Communication Model of Lung Evolution Traces Contemporary Phenotypes Back to Ancestral Phenotypes 43Predictive Value of the Lung Cell–Cell Communication Model for Understanding the Evolution of Physiologic Systems 44Sexual Dimorphism of Lung Development: A Case Study in Cell–Cell Communication and Evolutionary Plasticity 46Androgen Affects the Expression of Growth Factors Involved in Lung Development 48Evidence for an Association between Steroid-Resistant/Responsive Phenotypes and Human Lymphocyte Antigen (HLA) Haplotypes 495 HOW TO INTEGRATE CELL-MOLECULAR DEVELOPMENT, HOMEOSTASIS, ECOLOGY, AND EVOLUTIONARY BIOLOGY: THE MISSING LINKS 53Neutral Theory versus Intelligent Design 54Internal Selection Theory 54The Counterintuitive Nature of Physiology and Solution to the Dead Sea Scrolls Puzzle 57The Continuum from Microevolution to Macroevolution 58cis Regulation and Adaptive Evolution 69Evolution of cis Regulatory Mechanisms 706 FROM CELL–CELL COMMUNICATION TO THE EVOLUTION OF INTEGRATED PHYSIOLOGY 75Cell–cell Signaling and Alveolar Development: A Reductionist Approach to the Evolution of Physiologic Traits 77An Integrated, Empiric, Middle–Out Approach to Physiology 79A Molecular Evolutionary Link between the Lung and the Kidney? 82The Berner Hypothesis and Emergence of the Adipocyte: The Evolutionary Origins of the Lipofi broblast 83Lung Biology as a Cipher for Evolution 85Do Stretch Effects on PTHrP Expression Reflect Its Role in Adapting to Gravity? 85Wolff’s Law Works for Both Bone and Lung 88Functional Relationship between the External and Internal Environments 89An Evolutionary Vertical Integration of the Phylogeny and Ontogeny of the Thyroid 917 EXPLOITING CELL–CELL COMMUNICATION ACROSS SPACETIME TO DECONSTRUCT EVOLUTION 95Somewhere between the Gene and the Phenotype Lies the Process of Evolution 98A Functional Genomic Approach to Evolution as an Example of Terminal Addition 100Seeking Deep Homologies in Lung Evolution 102Systems Biology Based on Cell–Cell Communication 105Vertical Integration of Leptin Signaling, Human Evolution, and the Trojan Horse Effect 108Leptin and Human Evolution: Food for Thought 1098 THE PERIODIC TABLE OF BIOLOGY 115The Prospect of a Periodic Table of Biology 115Cellular Cooperation Is Key 116Elemental Biology 118PTHrP as an Archetype 118Evolution as the Solution 119Ramping Up a Mathematical Model of Evolution 121The Anthropic Principle Results from the Evolution of Cell–Cell Interactions 1249 VALUE ADDED BY THINKING IN TERMS OF THE CELL–CELL COMMUNICATION MODEL FOR EVOLUTION 125This is Not a Just-So Story 126Beyond Genomics 128From Fat Cells to Integrated Physiology 128Molecular Homologies Distinguish between the Evolutionary Forest and Trees 129The Oxygen–Cholesterol–Surfactant–Membrane Connection 130Cholesterol Metabolism as the Data Operating System for Vertebrate Biology? 131Translation of Genomics into the Periodic Table for Biology 132Deep Homologies 134Selection Pressure for Cell–Cell Communication: The Key to Understanding Evolution 13510 CELL–CELL COMMUNICATION AS THE BASIS FOR PRACTICING CLINICAL MEDICINE 139Cell–Cell Communication Maintenance and Breakdown Represent Heath and Disease, Respectively 140Cell–Cell Communications as a Framework for Human Evolution 140Canalization, Decanalization, and the Holistic Approach to the Practice of Medicine 141Exploiting Lung Evolution to Prevent and Treat Chronic Lung Disease 141Lung Evolution Explains the Magic of Continuous Positive Airway Pressure 142The Paradox of Infecting the Lung in Order to Treat Lung Disease Caused by Infection 143Exploiting Lung Evolution to Prevent and Treat Smoking-Related Lung Damage 144The Trojan Horse Effect of Canalization 145Impetus for Evolutionary Science as an Integral Part of the Clinical Curriculum 146Application of Evolutionary Science to Bioethics 147Evolutionary Science, a Biologic Periodic Table, and a Unifi ed Theory of Biology 148Summary 149Name Index 151Subject Index 153

John Torday, PhD, is Professor of Pediatrics and Ob/Gyn at Harbor-UCLA Medical Center where he is also Director of The Henry L. Guenther Laboratory for Cell/Molecular Research and Director of Laboratory for Evolutionary Preventive Medicine.  He is the author of over 130 peer-reviewed articles, Dr. Torday specializes in pre and neo-natal lung development, particularly regarding cell-cell communication within this pathway. V.K. Rehan, MD, is Professor of Pediatrics and Director of the Neonatal Intensive Care Unit at Harbor-UCLA Medical Center.  The recipient of numerous teaching honors, Dr. Rehan is involved both in treating patients and continuing research on neo and peri-natal respiratory issues and lung development.

"…the book offers the biology-savvy reader with interesting insights into the contribution of cell-cell interactions to the development and evolution of phenotypes.  Given the technical nature of the subject, this book will have particular appeal among researchers and students of cellular and molecular biology and among evolutionary biologists interested in the pathways linking genes to phenotypes.  In keeping with the complexity of the topic, there is much to digest here, and readers knowledgeable in these fields will find interesting food for thought.”  (Quarterly Reviews in Biology, 1  July 2013)

• Preface xi About the Authors xiii1 THE CELLULAR ORIGIN OF VERTEBRATES 1The Origins of Unicellular Life on Earth 1Prokaryotes versus Eukaryotes 4Coevolution of traits 5Cholesterol Facilitates Lipid Rafts for Cell–Cell Communication 7The Endomembrane System 9The Cellular Mechanism of Evolution 10Why Evolve? 11Cell–Cell Communication and Aging 122 REDUCING LUNG PHYSIOLOGY TO ITS MOLECULAR PHENOTYPES 17Hormonal Acceleration of Lung Development 17Neutral Lipid Traffi cking and Lung Evolution 19Other Examples of Cellular Cooperativity 23Summary 243 A CELL–MOLECULAR STRATEGY FOR SOLVING THE EVOLUTIONARY PUZZLE 25Rationale for Cell–Molecular Evolution 25Mechanism of Mammalian Lung Development 28Avian Lung Structure–Function Relationship: The Exception that Proves the Rule 32Does Ontogeny Recapitulate Phylogeny? The Role of PTHrP in Lung Development 32Interrelationship between PTHrP, Development, Physiology, and Repair: Is Repair a Recapitulation of Ontogeny and Phylogeny? 334 THE EVOLUTION OF CELL–CELL COMMUNICATION 35Cell–Cell Communication as the Mechanistic Basis for Evolutionary Biology 36The Darwinian Biologic Spacetime Continuum and Einstein’s Vision of the Universe 37Reverse Engineering of Physiologic Traits as a Portal for Viewing Evolution 38Cell–Cell Communication as the Basis for the Evolution of Metazoans 41Understanding Lung Evolution from the Middle Out 42The Cell–Cell Communication Model of Lung Evolution Traces Contemporary Phenotypes Back to Ancestral Phenotypes 43Predictive Value of the Lung Cell–Cell Communication Model for Understanding the Evolution of Physiologic Systems 44Sexual Dimorphism of Lung Development: A Case Study in Cell–Cell Communication and Evolutionary Plasticity 46Androgen Affects the Expression of Growth Factors Involved in Lung Development 48Evidence for an Association between Steroid-Resistant/Responsive Phenotypes and Human Lymphocyte Antigen (HLA) Haplotypes 495 HOW TO INTEGRATE CELL-MOLECULAR DEVELOPMENT, HOMEOSTASIS, ECOLOGY, AND EVOLUTIONARY BIOLOGY: THE MISSING LINKS 53Neutral Theory versus Intelligent Design 54Internal Selection Theory 54The Counterintuitive Nature of Physiology and Solution to the Dead Sea Scrolls Puzzle 57The Continuum from Microevolution to Macroevolution 58cis Regulation and Adaptive Evolution 69Evolution of cis Regulatory Mechanisms 706 FROM CELL–CELL COMMUNICATION TO THE EVOLUTION OF INTEGRATED PHYSIOLOGY 75Cell–cell Signaling and Alveolar Development: A Reductionist Approach to the Evolution of Physiologic Traits 77An Integrated, Empiric, Middle–Out Approach to Physiology 79A Molecular Evolutionary Link between the Lung and the Kidney? 82The Berner Hypothesis and Emergence of the Adipocyte: The Evolutionary Origins of the Lipofi broblast 83Lung Biology as a Cipher for Evolution 85Do Stretch Effects on PTHrP Expression Reflect Its Role in Adapting to Gravity? 85Wolff’s Law Works for Both Bone and Lung 88Functional Relationship between the External and Internal Environments 89An Evolutionary Vertical Integration of the Phylogeny and Ontogeny of the Thyroid 917 EXPLOITING CELL–CELL COMMUNICATION ACROSS SPACETIME TO DECONSTRUCT EVOLUTION 95Somewhere between the Gene and the Phenotype Lies the Process of Evolution 98A Functional Genomic Approach to Evolution as an Example of Terminal Addition 100Seeking Deep Homologies in Lung Evolution 102Systems Biology Based on Cell–Cell Communication 105Vertical Integration of Leptin Signaling, Human Evolution, and the Trojan Horse Effect 108Leptin and Human Evolution: Food for Thought 1098 THE PERIODIC TABLE OF BIOLOGY 115The Prospect of a Periodic Table of Biology 115Cellular Cooperation Is Key 116Elemental Biology 118PTHrP as an Archetype 118Evolution as the Solution 119Ramping Up a Mathematical Model of Evolution 121The Anthropic Principle Results from the Evolution of Cell–Cell Interactions 1249 VALUE ADDED BY THINKING IN TERMS OF THE CELL–CELL COMMUNICATION MODEL FOR EVOLUTION 125This is Not a Just-So Story 126Beyond Genomics 128From Fat Cells to Integrated Physiology 128Molecular Homologies Distinguish between the Evolutionary Forest and Trees 129The Oxygen–Cholesterol–Surfactant–Membrane Connection 130Cholesterol Metabolism as the Data Operating System for Vertebrate Biology? 131Translation of Genomics into the Periodic Table for Biology 132Deep Homologies 134Selection Pressure for Cell–Cell Communication: The Key to Understanding Evolution 13510 CELL–CELL COMMUNICATION AS THE BASIS FOR PRACTICING CLINICAL MEDICINE 139Cell–Cell Communication Maintenance and Breakdown Represent Heath and Disease, Respectively 140Cell–Cell Communications as a Framework for Human Evolution 140Canalization, Decanalization, and the Holistic Approach to the Practice of Medicine 141Exploiting Lung Evolution to Prevent and Treat Chronic Lung Disease 141Lung Evolution Explains the Magic of Continuous Positive Airway Pressure 142The Paradox of Infecting the Lung in Order to Treat Lung Disease Caused by Infection 143Exploiting Lung Evolution to Prevent and Treat Smoking-Related Lung Damage 144The Trojan Horse Effect of Canalization 145Impetus for Evolutionary Science as an Integral Part of the Clinical Curriculum 146Application of Evolutionary Science to Bioethics 147Evolutionary Science, a Biologic Periodic Table, and a Unifi ed Theory of Biology 148Summary 149Name Index 151Subject Index 153