Stoyan Smoukov, PhD, is a Professor at Queen Mary University of London, leading the Active & Intelligent Materials (AIM) Lab (previously from 2012-2017 at the University of Cambridge). He has led pioneering research in multi-functional materials with the support of the prestigious European Research Council individual ERC grant. His focus on bottom-up design for inanimate materials has yielded novel artificial muscles, supercapacitors, multifunctional materials which can replace whole devices, the discovery of artificial morphogenesis, and combinatorial approaches to multi-functionality. Prof. Smoukov has published more than 95 journal papers, cited over 4000 times, with an H-index of 35. Joseph Seckbach, PhD, is a retired senior academician at The Hebrew University of Jerusalem, Israel. He earned his PhD from the University of Chicago and did a post-doctorate in the Division of Biology at Caltech, in Pasadena, CA. He served at Louisiana State University (LSU), Baton Rouge, LA, USA, as the first selected Chair for the Louisiana Sea Grant and Technology transfer. Professor Joseph Seckbach has edited over 40 scientific books and authored about 140 scientific articles. Richard Gordon, PhD, is a theoretical biologist who retired from the Department of Radiology, University of Manitoba in 2011. Presently he is at Gulf Specimen Marine Lab & Aquarium, Panacea, Florida. His interest in exobiology (now astrobiology) dates from 1960s undergraduate work on organic matter in the Orgueil meteorite with Edward Anders. He has published critical reviews of panspermia and the history of discoveries of life in meteorites, and with Stoyan Smoukov, worked on shaped droplets supporting the Archaea First Hypothesis.

• Foreword, “Are There Men on the Moon?” by Winston S. Churchill xiiiPreface xixAppendix to Preface by Richard Gordon and George Mikhailovsky xxvPart I: Introduction to the Origin of Life Puzzle 11 Origin of Life: Conflicting Models for the Origin of Life 3Sohan Jheeta and Elias Chatzitheodoridis1.1 Introduction 31.2 Top-Down Approach—The Phylogenetic Tree of Life 61.3 Bottom-Up Approach—The Hypotheses 111.4 The Emergence of Chemolithoautotrophs and Photolithoautotrophs? 191.5 Viruses: The Fourth Domain of Life? 221.6 Where are We with the Origin of Life on Earth? 25References 252 Characterizing Life: Four Dimensions and their Relevance to Origin of Life Research 33Emily C. Parke2.1 Introduction 332.2 The Debate About (Defining) Life 352.2.1 The Debate and the Meta-Debate 352.2.2 Defining Life is Only One Way to Address the Question “What is Life?” 372.3 Does Origin of Life Research Need a Characterization of Life? 392.4 Dimensions of Characterizing Life 412.4.1 Dimension 1: Dichotomy or Matter of Degree? 412.4.2 Dimension 2: Material or Functional? 432.4.3 Dimension 3: Individual or Collective? 442.4.4 Dimension 4: Minimal or Inclusive 462.4.5 Summary Discussion of the Dimensions 472.5 Conclusion 48Acknowledgments 48References 483 Emergence, Construction, or Unlikely? Navigating the Space of Questions Regarding Life’s Origins 53Stuart Bartlett and Michael L. Wong3.1 How Can We Approach the Origins Quest(ion)? 533.2 Avian Circularities 543.3 Assuming That 563.4 Unlikely 563.5 Construction 583.6 Emergence 60References 63Part II: Chemistry Approaches 654 The Origin of Metabolism and GADV Hypothesis on the Origin of Life 67Kenji Ikehara4.1 Introduction 684.2 [GADV]-Amino Acids and Protein 0th-Order Structure 704.3 Exploration of the Initial Metabolism: The Origin of Metabolism 714.3.1 From What Kind of Enzymatic Reactions Did the Metabolic System Originate? 714.3.2 What Kind of Organic Compounds Accumulated on the Primitive Earth 724.3.3 What Organic Compounds were Required for the First Life to Emerge? 744.4 From Reactions Using What Kind of Organic Compounds Did the Metabolism Originate? 754.4.1 Catalytic Reactions with What Kind of Organic Compounds Were Incorporated Into the Initial Metabolism? 764.4.2 Search for Metabolic Reactions Incorporated Into the Initial Metabolism 764.4.3 Syntheses of [GADV]-Amino Acids Leading to Produce [GADV]-Proteins/Peptides Were One of the Most Important Matters for the First Life 764.4.4 Nucleotide Synthetic Pathways were Integrated at the Second Phase in the Initial Metabolism 784.5 Discussion 804.5.1 Protein 0 th -Order Structure Was the Key for Solving the Origin of Metabolism 804.5.2 Validity of GPG-Three Compounds Hypothesis on the Origin of Metabolism 824.5.3 Establishment of the Metabolic System and the Emergence of Life 834.5.4 The Emergence of Life Viewed from the Origin of Metabolism 84Acknowledgments 85References 865 Chemical Automata at the Origins of Life 89André Brack5.1 Introduction 895.2 Theoretical Models 905.2.1 The Chemoton Model 905.2.2 Autopoiesis 905.2.3 Biotic Abstract Dual Automata 915.2.4 Automata and Diffusion-Controlled Reactions 915.2.5 Quasi-Species and Hypercycle 915.2.6 Computer Modeling 915.2.7 Two-Dimensional Automata 925.3 Experimental Approach 925.3.1 The Ingredients for Life 925.3.2 Capabilities Required for the Chemical Automata 935.3.2.1 Autonomy 935.3.2.2 Self-Ordering and Self-Organization 935.3.2.3 About Discriminating Aggregation 945.3.2.4 Autocatalysis and Competition 955.4 Conclusion 95References 966 A Universal Chemical Constructor to Explore the Nature and Origin of Life 101Geoffrey J. T. Cooper, Sara I. Walker and Leroy Cronin6.1 Introduction 1026.2 Digitization of Chemistry 1096.3 Environmental Programming, Recursive Cycles, and Protocells 1176.4 Measuring Complexity and Chemical Selection Engines 1226.5 Constructing a Chemical Selection Engine 125Acknowledgements 126References 1267 How to Make a Transmembrane Domain at the Origin of Life: A Possible Origin of Proteins 131Richard Gordon and Natalie K. Gordon7.1 Introduction 1317.2 The Initial “Core” Amino Acids 1327.3 The Thickness of Membranes of the First Vesicles 1427.4 Carbon–Carbon Distances Perpendicular to a Membrane 1447.5 The Thickness of Modern Membranes 1447.6 A Prebiotic Model for the Coordinated Growth of Membrane Thickness and Transmembrane Peptides 1457.7 A Model for the Coordinated Growth of Membrane Thickness and Transmembrane Peptides 1487.8 RNA World with the Protein World 1507.9 Conclusion 153Acknowledgements 154References 155Part III: Physics Approaches 1758 Patterns that Persist: Heritable Information in Stochastic Dynamics 177Peter M. Tzelios and Kyle J. M. Bishop8.1 Introduction 1788.2 Markov Processes 1818.2.1 Simple Examples of Markov Processes 1818.2.2 Stochastic Dynamics 1838.2.3 Master Equation 1858.2.4 Dynamic Persistence 1868.2.5 Coarse Graining 1878.2.6 Entropy Production 1888.3 Results 1898.3.1 The Persistence Filter 1898.4 Mechanisms of Persistence 1908.5 Effects of Size N and Disequilibrium γ 1928.6 Probability of Persistence 1948.6.1 Continuity Constraint 1958.6.2 Locality Constraint 1968.6.3 New Strategies for Persistence 1978.7 Measuring Persistence in Practice 1988.7.1 Computable Information Density (CID) 1988.7.2 Quantifying Persistence in Dynamic Assemblies of Colloidal Rollers 2008.8 Conclusions 2038.9 Methods 2058.9.1 Coarse-Graining 2058.10 Monte Carlo Optimization 2068.11 Experiments on Ferromagnetic Rollers 2068.12 A Persistence in Equilibrium Systems 207Acknowledgements 209References 2099 When We Were Triangles: Shape in the Origin of Life via Abiotic, Shaped Droplets to Living, Polygonal Archaea During the Abiocene 213Richard Gordon9.1 Introduction 2139.1.1 What Correlates with Archaea Shape? Nothing! 2149.1.2 Archaea’s Place in the Tree of Life 2199.1.3 The Discovery and Exploration of Shaped Droplets 2229.1.4 Shaped Droplets as Protocells 2239.1.5 Comparison of Shaped Droplets with Archaea 2239.1.6 The S-Layer 2249.1.7 The S-Layer as a Two-Dimensional Liquid with Fault Lines 2249.1.8 The Analogy of the S-Layer to Bubble Rafts 2299.1.9 Energy Minimization Model for the S-Layer in Polygonal Archaea 2299.2 Discussion 2369.3 Conclusion 240Acknowledgements 240References 24010 Challenges and Perspectives of Robot Inventors that Autonomously Design, Build, and Test Physical Robots 263Fumiya Iida, Toby Howison, Simon Hauser and Josie Hughes10.1 Introduction 26310.2 Physical Evolutionary-Developmental Robotics 26410.2.1 Robotic Invention 26510.2.2 Physical Morphology Adaptation 26610.3 Falling Paper Design Experiments 26910.3.1 Design–Behavior Mapping 27010.3.2 More Variations of Paper Falling Patterns 27210.3.3 Characterizing Falling Paper Behaviors 27410.4 Evolutionary Dynamics of Collective Bernoulli Balloons 27410.5 Discussions and Conclusions 276Acknowledgments 277References 277Part IV: The Approach of Creating Life 27911 Synthetic Cells: A Route Toward Assembling Life 281Antoni Llopis-Lorente, N. Amy Yewdall, Alexander F. Mason, Loai K. E. A. Abdelmohsen and Jan C. M. van Hest11.1 Compartmentalization: Putting Life in a Box 28211.2 The Making of Cell-Sized Giant Liposomes 28311.3 Coacervate-Based Synthetic Cells 28511.4 Adaptivity and Functionality in Synthetic Cells 28811.5 Synthetic Cell Information Processing and Communication 29111.6 Intracellular Information Processing: Making Decisions with All the Noise 29211.7 Extracellular Communication: the Art of Talking and Selective Listening 29411.8 Conclusions 296Acknowledgments 296References 29712 Origin of Life from a Maker’s Perspective–Focus on Protocellular Compartments in Bottom-Up Synthetic Biology 303Ivan Ivanov, Stoyan K. Smoukov, Ehsan Nourafkan, Katharina Landfester and Petra Schwille12.1 Introduction 30312.2 Unifying the Plausible Protocells in Line with the Crowded Cell 30912.3 Self-Sustained Cycles of Growth and Division 31112.4 Transport and Energy Generation at the Interface 31412.4.1 Energy and Complexity 31512.4.2 Energy Compartmentation 31612.5 Synergistic Effects Towards the Origin of Life 319References 320Part V: When and Where Did Life Start? 32713 A Nuclear Geyser Origin of Life: Life Assembly Plant – Three-Step Model for the Emergence of the First Life on Earth and Cell Dynamics for the Coevolution of Life’s Functions 329Shigenori Maruyama and Toshikazu Ebisuzaki13.1 Introduction 33013.2 Natural Nuclear Reactor 33113.2.1 Principle of a Natural Nuclear Reactor 33113.2.2 Natural Nuclear Reactor in Gabon 33213.2.3 Radiation Chemistry to Produce Organics 33313.2.4 Hadean Natural Nuclear Reactor 33413.3 Nuclear Geyser Model as a Birthplace of Life on the Hadean Earth 33613.4 Nine Requirements for the Birthplace of Life 33813.5 Three-Step Model for the Emergence of the First Life on Hadean Earth 34013.5.1 The Emergence of the First Proto-Life 34113.5.1.1 Domain I: Inorganics 34213.5.1.2 Domain II: From Inorganic to Organic 34213.5.1.3 Domain III: Production of More Advanced BBL 34313.5.1.4 Domain IV: Passage Connecting Geyser Main Room with the Surface and Fountain Flow 34313.5.1.5 Domain V: Production of BBL in an Oxidizing Wet–Dry Surface Environment 34513.5.1.6 Domain VI: Birthplace of the First Proto-Life 34613.5.1.7 Utilization of Metallic Proteins 34713.5.2 The Emergence of the Second Proto-Life 34813.5.2.1 Drastic Environmental Change from Step 1 to Step 2 34813.5.2.2 Biological Response from Step 1 to Step 2 34913.5.3 The Emergence of the Third Proto-Life, Prokaryote 35013.5.3.1 Drastic Environmental Changes from Step 2 to Step 3 35013.5.3.2 Biological Response from Step 2 to Step 3 35113.6 Concept of the Cell Dynamics: Life Assembly Plant 353Acknowledgments 356References 35614 Comments on the Nuclear Geyser Origin of Life Proposal of the Authors S. Maruyama and T. Ebisuzaki and Interstellar Medium as a Possible Birthplace of Life 361Jaroslav JiøíkReferences 36615 Nucleotide Photochemistry on the Early Earth 369Whitaker, D. E., Colville, B.W.F. and Powner, M. W.15.1 Introduction 36915.2 Pyrimidine Photochemistry 37215.2.1 Photohydrates 37215.2.2 Photodimers 37415.2.3 Glycosidic Bond Cleavage 37615.2.4 Addition of Nucleophiles to C 2 37815.3 Purine Photochemistry 38015.4 Photochemistry of Noncanonical Nucleosides 38215.4.1 Photochemical Anomerization of Cytidine Nucleosides 38315.4.2 Thiobase Irradiation Products 38715.4.3 Photochemical Decarboxylation of Orotidine 39015.4.4 Photochemical Synthesis of AICN, a Possible Synthetic Precursor to the Purines 39115.5 Considering More Complex Photochemical Systems 39215.6 Concluding Remarks 395References 39516 Origins of Life on Exoplanets 407Paul B. Rimmer16.1 Introduction 40716.2 How to Test Origins Hypotheses 40816.3 Exoplanets as Laboratories 41016.4 The Scenario 41216.5 Initial Conditions 41416.5.1 Chemical Initial Conditions 41416.5.1.1 Hydrogen Cyanide 41416.5.1.2 Sulfite and Sulfide 41516.5.2 Physical Initial Conditions 41516.6 Chances of Success 41716.7 Relevance of the Outcome 42016.8 Conclusions 420Acknowledgements 421References 42117 The Fish Ladder Toy Model for a Thermodynamically at Equilibrium Origin of Life in a Lipid World in an Endoreic Lake 425Richard Gordon, Shruti Raj Vansh Singh, Krishna Katyal and Natalie K. Gordon17.1 The Fish Ladder Model for the Origin of Life 42617.2 Could the Late Heavy Bombardment have Supplied Enough Amphiphiles? 43517.3 How Many Uphill Steps to LUCA? 43817.4 How Long Would the Origin of Life Take After the CVC is Achieved? 44017.5 Conclusion 440Acknowledgements 443Appendix (Discussion with David Deamer) 443References 447Index 459

Stoyan Smoukov, PhD, is a Professor at Queen Mary University of London, leading the Active & Intelligent Materials (AIM) Lab (previously from 2012-2017 at the University of Cambridge). He has led pioneering research in multi-functional materials with the support of the prestigious European Research Council individual ERC grant. His focus on bottom-up design for inanimate materials has yielded novel artificial muscles, supercapacitors, multifunctional materials which can replace whole devices, the discovery of artificial morphogenesis, and combinatorial approaches to multi-functionality. Prof. Smoukov has published more than 95 journal papers, cited over 4000 times, with an H-index of 35. Joseph Seckbach, PhD, is a retired senior academician at The Hebrew University of Jerusalem, Israel. He earned his PhD from the University of Chicago and did a post-doctorate in the Division of Biology at Caltech, in Pasadena, CA. He served at Louisiana State University (LSU), Baton Rouge, LA, USA, as the first selected Chair for the Louisiana Sea Grant and Technology transfer. Professor Joseph Seckbach has edited over 40 scientific books and authored about 140 scientific articles. Richard Gordon, PhD, is a theoretical biologist who retired from the Department of Radiology, University of Manitoba in 2011. Presently he is at Gulf Specimen Marine Lab & Aquarium, Panacea, Florida. His interest in exobiology (now astrobiology) dates from 1960s undergraduate work on organic matter in the Orgueil meteorite with Edward Anders. He has published critical reviews of panspermia and the history of discoveries of life in meteorites, and with Stoyan Smoukov, worked on shaped droplets supporting the Archaea First Hypothesis.

• Foreword, “Are There Men on the Moon?” by Winston S. Churchill xiiiPreface xixAppendix to Preface by Richard Gordon and George Mikhailovsky xxvPart I: Introduction to the Origin of Life Puzzle 11 Origin of Life: Conflicting Models for the Origin of Life 3Sohan Jheeta and Elias Chatzitheodoridis1.1 Introduction 31.2 Top-Down Approach—The Phylogenetic Tree of Life 61.3 Bottom-Up Approach—The Hypotheses 111.4 The Emergence of Chemolithoautotrophs and Photolithoautotrophs? 191.5 Viruses: The Fourth Domain of Life? 221.6 Where are We with the Origin of Life on Earth? 25References 252 Characterizing Life: Four Dimensions and their Relevance to Origin of Life Research 33Emily C. Parke2.1 Introduction 332.2 The Debate About (Defining) Life 352.2.1 The Debate and the Meta-Debate 352.2.2 Defining Life is Only One Way to Address the Question “What is Life?” 372.3 Does Origin of Life Research Need a Characterization of Life? 392.4 Dimensions of Characterizing Life 412.4.1 Dimension 1: Dichotomy or Matter of Degree? 412.4.2 Dimension 2: Material or Functional? 432.4.3 Dimension 3: Individual or Collective? 442.4.4 Dimension 4: Minimal or Inclusive 462.4.5 Summary Discussion of the Dimensions 472.5 Conclusion 48Acknowledgments 48References 483 Emergence, Construction, or Unlikely? Navigating the Space of Questions Regarding Life’s Origins 53Stuart Bartlett and Michael L. Wong3.1 How Can We Approach the Origins Quest(ion)? 533.2 Avian Circularities 543.3 Assuming That 563.4 Unlikely 563.5 Construction 583.6 Emergence 60References 63Part II: Chemistry Approaches 654 The Origin of Metabolism and GADV Hypothesis on the Origin of Life 67Kenji Ikehara4.1 Introduction 684.2 [GADV]-Amino Acids and Protein 0th-Order Structure 704.3 Exploration of the Initial Metabolism: The Origin of Metabolism 714.3.1 From What Kind of Enzymatic Reactions Did the Metabolic System Originate? 714.3.2 What Kind of Organic Compounds Accumulated on the Primitive Earth 724.3.3 What Organic Compounds were Required for the First Life to Emerge? 744.4 From Reactions Using What Kind of Organic Compounds Did the Metabolism Originate? 754.4.1 Catalytic Reactions with What Kind of Organic Compounds Were Incorporated Into the Initial Metabolism? 764.4.2 Search for Metabolic Reactions Incorporated Into the Initial Metabolism 764.4.3 Syntheses of [GADV]-Amino Acids Leading to Produce [GADV]-Proteins/Peptides Were One of the Most Important Matters for the First Life 764.4.4 Nucleotide Synthetic Pathways were Integrated at the Second Phase in the Initial Metabolism 784.5 Discussion 804.5.1 Protein 0 th -Order Structure Was the Key for Solving the Origin of Metabolism 804.5.2 Validity of GPG-Three Compounds Hypothesis on the Origin of Metabolism 824.5.3 Establishment of the Metabolic System and the Emergence of Life 834.5.4 The Emergence of Life Viewed from the Origin of Metabolism 84Acknowledgments 85References 865 Chemical Automata at the Origins of Life 89André Brack5.1 Introduction 895.2 Theoretical Models 905.2.1 The Chemoton Model 905.2.2 Autopoiesis 905.2.3 Biotic Abstract Dual Automata 915.2.4 Automata and Diffusion-Controlled Reactions 915.2.5 Quasi-Species and Hypercycle 915.2.6 Computer Modeling 915.2.7 Two-Dimensional Automata 925.3 Experimental Approach 925.3.1 The Ingredients for Life 925.3.2 Capabilities Required for the Chemical Automata 935.3.2.1 Autonomy 935.3.2.2 Self-Ordering and Self-Organization 935.3.2.3 About Discriminating Aggregation 945.3.2.4 Autocatalysis and Competition 955.4 Conclusion 95References 966 A Universal Chemical Constructor to Explore the Nature and Origin of Life 101Geoffrey J. T. Cooper, Sara I. Walker and Leroy Cronin6.1 Introduction 1026.2 Digitization of Chemistry 1096.3 Environmental Programming, Recursive Cycles, and Protocells 1176.4 Measuring Complexity and Chemical Selection Engines 1226.5 Constructing a Chemical Selection Engine 125Acknowledgements 126References 1267 How to Make a Transmembrane Domain at the Origin of Life: A Possible Origin of Proteins 131Richard Gordon and Natalie K. Gordon7.1 Introduction 1317.2 The Initial “Core” Amino Acids 1327.3 The Thickness of Membranes of the First Vesicles 1427.4 Carbon–Carbon Distances Perpendicular to a Membrane 1447.5 The Thickness of Modern Membranes 1447.6 A Prebiotic Model for the Coordinated Growth of Membrane Thickness and Transmembrane Peptides 1457.7 A Model for the Coordinated Growth of Membrane Thickness and Transmembrane Peptides 1487.8 RNA World with the Protein World 1507.9 Conclusion 153Acknowledgements 154References 155Part III: Physics Approaches 1758 Patterns that Persist: Heritable Information in Stochastic Dynamics 177Peter M. Tzelios and Kyle J. M. Bishop8.1 Introduction 1788.2 Markov Processes 1818.2.1 Simple Examples of Markov Processes 1818.2.2 Stochastic Dynamics 1838.2.3 Master Equation 1858.2.4 Dynamic Persistence 1868.2.5 Coarse Graining 1878.2.6 Entropy Production 1888.3 Results 1898.3.1 The Persistence Filter 1898.4 Mechanisms of Persistence 1908.5 Effects of Size N and Disequilibrium γ 1928.6 Probability of Persistence 1948.6.1 Continuity Constraint 1958.6.2 Locality Constraint 1968.6.3 New Strategies for Persistence 1978.7 Measuring Persistence in Practice 1988.7.1 Computable Information Density (CID) 1988.7.2 Quantifying Persistence in Dynamic Assemblies of Colloidal Rollers 2008.8 Conclusions 2038.9 Methods 2058.9.1 Coarse-Graining 2058.10 Monte Carlo Optimization 2068.11 Experiments on Ferromagnetic Rollers 2068.12 A Persistence in Equilibrium Systems 207Acknowledgements 209References 2099 When We Were Triangles: Shape in the Origin of Life via Abiotic, Shaped Droplets to Living, Polygonal Archaea During the Abiocene 213Richard Gordon9.1 Introduction 2139.1.1 What Correlates with Archaea Shape? Nothing! 2149.1.2 Archaea’s Place in the Tree of Life 2199.1.3 The Discovery and Exploration of Shaped Droplets 2229.1.4 Shaped Droplets as Protocells 2239.1.5 Comparison of Shaped Droplets with Archaea 2239.1.6 The S-Layer 2249.1.7 The S-Layer as a Two-Dimensional Liquid with Fault Lines 2249.1.8 The Analogy of the S-Layer to Bubble Rafts 2299.1.9 Energy Minimization Model for the S-Layer in Polygonal Archaea 2299.2 Discussion 2369.3 Conclusion 240Acknowledgements 240References 24010 Challenges and Perspectives of Robot Inventors that Autonomously Design, Build, and Test Physical Robots 263Fumiya Iida, Toby Howison, Simon Hauser and Josie Hughes10.1 Introduction 26310.2 Physical Evolutionary-Developmental Robotics 26410.2.1 Robotic Invention 26510.2.2 Physical Morphology Adaptation 26610.3 Falling Paper Design Experiments 26910.3.1 Design–Behavior Mapping 27010.3.2 More Variations of Paper Falling Patterns 27210.3.3 Characterizing Falling Paper Behaviors 27410.4 Evolutionary Dynamics of Collective Bernoulli Balloons 27410.5 Discussions and Conclusions 276Acknowledgments 277References 277Part IV: The Approach of Creating Life 27911 Synthetic Cells: A Route Toward Assembling Life 281Antoni Llopis-Lorente, N. Amy Yewdall, Alexander F. Mason, Loai K. E. A. Abdelmohsen and Jan C. M. van Hest11.1 Compartmentalization: Putting Life in a Box 28211.2 The Making of Cell-Sized Giant Liposomes 28311.3 Coacervate-Based Synthetic Cells 28511.4 Adaptivity and Functionality in Synthetic Cells 28811.5 Synthetic Cell Information Processing and Communication 29111.6 Intracellular Information Processing: Making Decisions with All the Noise 29211.7 Extracellular Communication: the Art of Talking and Selective Listening 29411.8 Conclusions 296Acknowledgments 296References 29712 Origin of Life from a Maker’s Perspective–Focus on Protocellular Compartments in Bottom-Up Synthetic Biology 303Ivan Ivanov, Stoyan K. Smoukov, Ehsan Nourafkan, Katharina Landfester and Petra Schwille12.1 Introduction 30312.2 Unifying the Plausible Protocells in Line with the Crowded Cell 30912.3 Self-Sustained Cycles of Growth and Division 31112.4 Transport and Energy Generation at the Interface 31412.4.1 Energy and Complexity 31512.4.2 Energy Compartmentation 31612.5 Synergistic Effects Towards the Origin of Life 319References 320Part V: When and Where Did Life Start? 32713 A Nuclear Geyser Origin of Life: Life Assembly Plant – Three-Step Model for the Emergence of the First Life on Earth and Cell Dynamics for the Coevolution of Life’s Functions 329Shigenori Maruyama and Toshikazu Ebisuzaki13.1 Introduction 33013.2 Natural Nuclear Reactor 33113.2.1 Principle of a Natural Nuclear Reactor 33113.2.2 Natural Nuclear Reactor in Gabon 33213.2.3 Radiation Chemistry to Produce Organics 33313.2.4 Hadean Natural Nuclear Reactor 33413.3 Nuclear Geyser Model as a Birthplace of Life on the Hadean Earth 33613.4 Nine Requirements for the Birthplace of Life 33813.5 Three-Step Model for the Emergence of the First Life on Hadean Earth 34013.5.1 The Emergence of the First Proto-Life 34113.5.1.1 Domain I: Inorganics 34213.5.1.2 Domain II: From Inorganic to Organic 34213.5.1.3 Domain III: Production of More Advanced BBL 34313.5.1.4 Domain IV: Passage Connecting Geyser Main Room with the Surface and Fountain Flow 34313.5.1.5 Domain V: Production of BBL in an Oxidizing Wet–Dry Surface Environment 34513.5.1.6 Domain VI: Birthplace of the First Proto-Life 34613.5.1.7 Utilization of Metallic Proteins 34713.5.2 The Emergence of the Second Proto-Life 34813.5.2.1 Drastic Environmental Change from Step 1 to Step 2 34813.5.2.2 Biological Response from Step 1 to Step 2 34913.5.3 The Emergence of the Third Proto-Life, Prokaryote 35013.5.3.1 Drastic Environmental Changes from Step 2 to Step 3 35013.5.3.2 Biological Response from Step 2 to Step 3 35113.6 Concept of the Cell Dynamics: Life Assembly Plant 353Acknowledgments 356References 35614 Comments on the Nuclear Geyser Origin of Life Proposal of the Authors S. Maruyama and T. Ebisuzaki and Interstellar Medium as a Possible Birthplace of Life 361Jaroslav JiøíkReferences 36615 Nucleotide Photochemistry on the Early Earth 369Whitaker, D. E., Colville, B.W.F. and Powner, M. W.15.1 Introduction 36915.2 Pyrimidine Photochemistry 37215.2.1 Photohydrates 37215.2.2 Photodimers 37415.2.3 Glycosidic Bond Cleavage 37615.2.4 Addition of Nucleophiles to C 2 37815.3 Purine Photochemistry 38015.4 Photochemistry of Noncanonical Nucleosides 38215.4.1 Photochemical Anomerization of Cytidine Nucleosides 38315.4.2 Thiobase Irradiation Products 38715.4.3 Photochemical Decarboxylation of Orotidine 39015.4.4 Photochemical Synthesis of AICN, a Possible Synthetic Precursor to the Purines 39115.5 Considering More Complex Photochemical Systems 39215.6 Concluding Remarks 395References 39516 Origins of Life on Exoplanets 407Paul B. Rimmer16.1 Introduction 40716.2 How to Test Origins Hypotheses 40816.3 Exoplanets as Laboratories 41016.4 The Scenario 41216.5 Initial Conditions 41416.5.1 Chemical Initial Conditions 41416.5.1.1 Hydrogen Cyanide 41416.5.1.2 Sulfite and Sulfide 41516.5.2 Physical Initial Conditions 41516.6 Chances of Success 41716.7 Relevance of the Outcome 42016.8 Conclusions 420Acknowledgements 421References 42117 The Fish Ladder Toy Model for a Thermodynamically at Equilibrium Origin of Life in a Lipid World in an Endoreic Lake 425Richard Gordon, Shruti Raj Vansh Singh, Krishna Katyal and Natalie K. Gordon17.1 The Fish Ladder Model for the Origin of Life 42617.2 Could the Late Heavy Bombardment have Supplied Enough Amphiphiles? 43517.3 How Many Uphill Steps to LUCA? 43817.4 How Long Would the Origin of Life Take After the CVC is Achieved? 44017.5 Conclusion 440Acknowledgements 443Appendix (Discussion with David Deamer) 443References 447Index 459

Stoyan Smoukov, PhD, is a Professor at Queen Mary University of London, leading the Active & Intelligent Materials (AIM) Lab (previously from 2012-2017 at the University of Cambridge). He has led pioneering research in multi-functional materials with the support of the prestigious European Research Council individual ERC grant. His focus on bottom-up design for inanimate materials has yielded novel artificial muscles, supercapacitors, multifunctional materials which can replace whole devices, the discovery of artificial morphogenesis, and combinatorial approaches to multi-functionality. Prof. Smoukov has published more than 95 journal papers, cited over 4000 times, with an H-index of 35. Joseph Seckbach, PhD, is a retired senior academician at The Hebrew University of Jerusalem, Israel. He earned his PhD from the University of Chicago and did a post-doctorate in the Division of Biology at Caltech, in Pasadena, CA. He served at Louisiana State University (LSU), Baton Rouge, LA, USA, as the first selected Chair for the Louisiana Sea Grant and Technology transfer. Professor Joseph Seckbach has edited over 40 scientific books and authored about 140 scientific articles. Richard Gordon, PhD, is a theoretical biologist who retired from the Department of Radiology, University of Manitoba in 2011. Presently he is at Gulf Specimen Marine Lab & Aquarium, Panacea, Florida. His interest in exobiology (now astrobiology) dates from 1960s undergraduate work on organic matter in the Orgueil meteorite with Edward Anders. He has published critical reviews of panspermia and the history of discoveries of life in meteorites, and with Stoyan Smoukov, worked on shaped droplets supporting the Archaea First Hypothesis.

• Foreword, “Are There Men on the Moon?” by Winston S. Churchill xiiiPreface xixAppendix to Preface by Richard Gordon and George Mikhailovsky xxvPart I: Introduction to the Origin of Life Puzzle 11 Origin of Life: Conflicting Models for the Origin of Life 3Sohan Jheeta and Elias Chatzitheodoridis1.1 Introduction 31.2 Top-Down Approach—The Phylogenetic Tree of Life 61.3 Bottom-Up Approach—The Hypotheses 111.4 The Emergence of Chemolithoautotrophs and Photolithoautotrophs? 191.5 Viruses: The Fourth Domain of Life? 221.6 Where are We with the Origin of Life on Earth? 25References 252 Characterizing Life: Four Dimensions and their Relevance to Origin of Life Research 33Emily C. Parke2.1 Introduction 332.2 The Debate About (Defining) Life 352.2.1 The Debate and the Meta-Debate 352.2.2 Defining Life is Only One Way to Address the Question “What is Life?” 372.3 Does Origin of Life Research Need a Characterization of Life? 392.4 Dimensions of Characterizing Life 412.4.1 Dimension 1: Dichotomy or Matter of Degree? 412.4.2 Dimension 2: Material or Functional? 432.4.3 Dimension 3: Individual or Collective? 442.4.4 Dimension 4: Minimal or Inclusive 462.4.5 Summary Discussion of the Dimensions 472.5 Conclusion 48Acknowledgments 48References 483 Emergence, Construction, or Unlikely? Navigating the Space of Questions Regarding Life’s Origins 53Stuart Bartlett and Michael L. Wong3.1 How Can We Approach the Origins Quest(ion)? 533.2 Avian Circularities 543.3 Assuming That 563.4 Unlikely 563.5 Construction 583.6 Emergence 60References 63Part II: Chemistry Approaches 654 The Origin of Metabolism and GADV Hypothesis on the Origin of Life 67Kenji Ikehara4.1 Introduction 684.2 [GADV]-Amino Acids and Protein 0th-Order Structure 704.3 Exploration of the Initial Metabolism: The Origin of Metabolism 714.3.1 From What Kind of Enzymatic Reactions Did the Metabolic System Originate? 714.3.2 What Kind of Organic Compounds Accumulated on the Primitive Earth 724.3.3 What Organic Compounds were Required for the First Life to Emerge? 744.4 From Reactions Using What Kind of Organic Compounds Did the Metabolism Originate? 754.4.1 Catalytic Reactions with What Kind of Organic Compounds Were Incorporated Into the Initial Metabolism? 764.4.2 Search for Metabolic Reactions Incorporated Into the Initial Metabolism 764.4.3 Syntheses of [GADV]-Amino Acids Leading to Produce [GADV]-Proteins/Peptides Were One of the Most Important Matters for the First Life 764.4.4 Nucleotide Synthetic Pathways were Integrated at the Second Phase in the Initial Metabolism 784.5 Discussion 804.5.1 Protein 0 th -Order Structure Was the Key for Solving the Origin of Metabolism 804.5.2 Validity of GPG-Three Compounds Hypothesis on the Origin of Metabolism 824.5.3 Establishment of the Metabolic System and the Emergence of Life 834.5.4 The Emergence of Life Viewed from the Origin of Metabolism 84Acknowledgments 85References 865 Chemical Automata at the Origins of Life 89André Brack5.1 Introduction 895.2 Theoretical Models 905.2.1 The Chemoton Model 905.2.2 Autopoiesis 905.2.3 Biotic Abstract Dual Automata 915.2.4 Automata and Diffusion-Controlled Reactions 915.2.5 Quasi-Species and Hypercycle 915.2.6 Computer Modeling 915.2.7 Two-Dimensional Automata 925.3 Experimental Approach 925.3.1 The Ingredients for Life 925.3.2 Capabilities Required for the Chemical Automata 935.3.2.1 Autonomy 935.3.2.2 Self-Ordering and Self-Organization 935.3.2.3 About Discriminating Aggregation 945.3.2.4 Autocatalysis and Competition 955.4 Conclusion 95References 966 A Universal Chemical Constructor to Explore the Nature and Origin of Life 101Geoffrey J. T. Cooper, Sara I. Walker and Leroy Cronin6.1 Introduction 1026.2 Digitization of Chemistry 1096.3 Environmental Programming, Recursive Cycles, and Protocells 1176.4 Measuring Complexity and Chemical Selection Engines 1226.5 Constructing a Chemical Selection Engine 125Acknowledgements 126References 1267 How to Make a Transmembrane Domain at the Origin of Life: A Possible Origin of Proteins 131Richard Gordon and Natalie K. Gordon7.1 Introduction 1317.2 The Initial “Core” Amino Acids 1327.3 The Thickness of Membranes of the First Vesicles 1427.4 Carbon–Carbon Distances Perpendicular to a Membrane 1447.5 The Thickness of Modern Membranes 1447.6 A Prebiotic Model for the Coordinated Growth of Membrane Thickness and Transmembrane Peptides 1457.7 A Model for the Coordinated Growth of Membrane Thickness and Transmembrane Peptides 1487.8 RNA World with the Protein World 1507.9 Conclusion 153Acknowledgements 154References 155Part III: Physics Approaches 1758 Patterns that Persist: Heritable Information in Stochastic Dynamics 177Peter M. Tzelios and Kyle J. M. Bishop8.1 Introduction 1788.2 Markov Processes 1818.2.1 Simple Examples of Markov Processes 1818.2.2 Stochastic Dynamics 1838.2.3 Master Equation 1858.2.4 Dynamic Persistence 1868.2.5 Coarse Graining 1878.2.6 Entropy Production 1888.3 Results 1898.3.1 The Persistence Filter 1898.4 Mechanisms of Persistence 1908.5 Effects of Size N and Disequilibrium γ 1928.6 Probability of Persistence 1948.6.1 Continuity Constraint 1958.6.2 Locality Constraint 1968.6.3 New Strategies for Persistence 1978.7 Measuring Persistence in Practice 1988.7.1 Computable Information Density (CID) 1988.7.2 Quantifying Persistence in Dynamic Assemblies of Colloidal Rollers 2008.8 Conclusions 2038.9 Methods 2058.9.1 Coarse-Graining 2058.10 Monte Carlo Optimization 2068.11 Experiments on Ferromagnetic Rollers 2068.12 A Persistence in Equilibrium Systems 207Acknowledgements 209References 2099 When We Were Triangles: Shape in the Origin of Life via Abiotic, Shaped Droplets to Living, Polygonal Archaea During the Abiocene 213Richard Gordon9.1 Introduction 2139.1.1 What Correlates with Archaea Shape? Nothing! 2149.1.2 Archaea’s Place in the Tree of Life 2199.1.3 The Discovery and Exploration of Shaped Droplets 2229.1.4 Shaped Droplets as Protocells 2239.1.5 Comparison of Shaped Droplets with Archaea 2239.1.6 The S-Layer 2249.1.7 The S-Layer as a Two-Dimensional Liquid with Fault Lines 2249.1.8 The Analogy of the S-Layer to Bubble Rafts 2299.1.9 Energy Minimization Model for the S-Layer in Polygonal Archaea 2299.2 Discussion 2369.3 Conclusion 240Acknowledgements 240References 24010 Challenges and Perspectives of Robot Inventors that Autonomously Design, Build, and Test Physical Robots 263Fumiya Iida, Toby Howison, Simon Hauser and Josie Hughes10.1 Introduction 26310.2 Physical Evolutionary-Developmental Robotics 26410.2.1 Robotic Invention 26510.2.2 Physical Morphology Adaptation 26610.3 Falling Paper Design Experiments 26910.3.1 Design–Behavior Mapping 27010.3.2 More Variations of Paper Falling Patterns 27210.3.3 Characterizing Falling Paper Behaviors 27410.4 Evolutionary Dynamics of Collective Bernoulli Balloons 27410.5 Discussions and Conclusions 276Acknowledgments 277References 277Part IV: The Approach of Creating Life 27911 Synthetic Cells: A Route Toward Assembling Life 281Antoni Llopis-Lorente, N. Amy Yewdall, Alexander F. Mason, Loai K. E. A. Abdelmohsen and Jan C. M. van Hest11.1 Compartmentalization: Putting Life in a Box 28211.2 The Making of Cell-Sized Giant Liposomes 28311.3 Coacervate-Based Synthetic Cells 28511.4 Adaptivity and Functionality in Synthetic Cells 28811.5 Synthetic Cell Information Processing and Communication 29111.6 Intracellular Information Processing: Making Decisions with All the Noise 29211.7 Extracellular Communication: the Art of Talking and Selective Listening 29411.8 Conclusions 296Acknowledgments 296References 29712 Origin of Life from a Maker’s Perspective–Focus on Protocellular Compartments in Bottom-Up Synthetic Biology 303Ivan Ivanov, Stoyan K. Smoukov, Ehsan Nourafkan, Katharina Landfester and Petra Schwille12.1 Introduction 30312.2 Unifying the Plausible Protocells in Line with the Crowded Cell 30912.3 Self-Sustained Cycles of Growth and Division 31112.4 Transport and Energy Generation at the Interface 31412.4.1 Energy and Complexity 31512.4.2 Energy Compartmentation 31612.5 Synergistic Effects Towards the Origin of Life 319References 320Part V: When and Where Did Life Start? 32713 A Nuclear Geyser Origin of Life: Life Assembly Plant – Three-Step Model for the Emergence of the First Life on Earth and Cell Dynamics for the Coevolution of Life’s Functions 329Shigenori Maruyama and Toshikazu Ebisuzaki13.1 Introduction 33013.2 Natural Nuclear Reactor 33113.2.1 Principle of a Natural Nuclear Reactor 33113.2.2 Natural Nuclear Reactor in Gabon 33213.2.3 Radiation Chemistry to Produce Organics 33313.2.4 Hadean Natural Nuclear Reactor 33413.3 Nuclear Geyser Model as a Birthplace of Life on the Hadean Earth 33613.4 Nine Requirements for the Birthplace of Life 33813.5 Three-Step Model for the Emergence of the First Life on Hadean Earth 34013.5.1 The Emergence of the First Proto-Life 34113.5.1.1 Domain I: Inorganics 34213.5.1.2 Domain II: From Inorganic to Organic 34213.5.1.3 Domain III: Production of More Advanced BBL 34313.5.1.4 Domain IV: Passage Connecting Geyser Main Room with the Surface and Fountain Flow 34313.5.1.5 Domain V: Production of BBL in an Oxidizing Wet–Dry Surface Environment 34513.5.1.6 Domain VI: Birthplace of the First Proto-Life 34613.5.1.7 Utilization of Metallic Proteins 34713.5.2 The Emergence of the Second Proto-Life 34813.5.2.1 Drastic Environmental Change from Step 1 to Step 2 34813.5.2.2 Biological Response from Step 1 to Step 2 34913.5.3 The Emergence of the Third Proto-Life, Prokaryote 35013.5.3.1 Drastic Environmental Changes from Step 2 to Step 3 35013.5.3.2 Biological Response from Step 2 to Step 3 35113.6 Concept of the Cell Dynamics: Life Assembly Plant 353Acknowledgments 356References 35614 Comments on the Nuclear Geyser Origin of Life Proposal of the Authors S. Maruyama and T. Ebisuzaki and Interstellar Medium as a Possible Birthplace of Life 361Jaroslav JiøíkReferences 36615 Nucleotide Photochemistry on the Early Earth 369Whitaker, D. E., Colville, B.W.F. and Powner, M. W.15.1 Introduction 36915.2 Pyrimidine Photochemistry 37215.2.1 Photohydrates 37215.2.2 Photodimers 37415.2.3 Glycosidic Bond Cleavage 37615.2.4 Addition of Nucleophiles to C 2 37815.3 Purine Photochemistry 38015.4 Photochemistry of Noncanonical Nucleosides 38215.4.1 Photochemical Anomerization of Cytidine Nucleosides 38315.4.2 Thiobase Irradiation Products 38715.4.3 Photochemical Decarboxylation of Orotidine 39015.4.4 Photochemical Synthesis of AICN, a Possible Synthetic Precursor to the Purines 39115.5 Considering More Complex Photochemical Systems 39215.6 Concluding Remarks 395References 39516 Origins of Life on Exoplanets 407Paul B. Rimmer16.1 Introduction 40716.2 How to Test Origins Hypotheses 40816.3 Exoplanets as Laboratories 41016.4 The Scenario 41216.5 Initial Conditions 41416.5.1 Chemical Initial Conditions 41416.5.1.1 Hydrogen Cyanide 41416.5.1.2 Sulfite and Sulfide 41516.5.2 Physical Initial Conditions 41516.6 Chances of Success 41716.7 Relevance of the Outcome 42016.8 Conclusions 420Acknowledgements 421References 42117 The Fish Ladder Toy Model for a Thermodynamically at Equilibrium Origin of Life in a Lipid World in an Endoreic Lake 425Richard Gordon, Shruti Raj Vansh Singh, Krishna Katyal and Natalie K. Gordon17.1 The Fish Ladder Model for the Origin of Life 42617.2 Could the Late Heavy Bombardment have Supplied Enough Amphiphiles? 43517.3 How Many Uphill Steps to LUCA? 43817.4 How Long Would the Origin of Life Take After the CVC is Achieved? 44017.5 Conclusion 440Acknowledgements 443Appendix (Discussion with David Deamer) 443References 447Index 459