Open-Endedness in Genelife.

We explore the open-ended nature of evolution in Genelife, an evolutionary extension of Conway's Game of Life cellular automaton in which "live" cell states are endowed at birth with a genome that affects their local dynamics and can be inherited. Both genetic sequences and locally connected spatial patterns are analyzed for novelty, keeping track of all new structures, and innovation is quantified using activity statistics. The impacts of both spatial symmetry breaking with nontotalistic rules and superimposed density regulation of the live state proliferation on the open-ended nature of the evolution are explored. Conditions are found where both genetic and spatial patterns exhibit open-ended innovation. This innovation appears to fall short of functional biological innovation, however, and potential reasons for this are discussed.

An Overview of Open-Ended Evolution: Editorial Introduction to the Open-Ended Evolution II Special Issue.

Nature's spectacular inventiveness, reflected in the enormous diversity of form and function displayed by the biosphere, is a feature of life that distinguishes living most strongly from nonliving. It is, therefore, not surprising that this aspect of life should become a central focus of artificial life. We have known since Darwin that the diversity is produced dynamically, through the process of evolution; this has led life's creative productivity to be called Open-Ended Evolution (OEE) in the field. This article introduces the second of two special issues on current research in OEE and provides an overview of the contents of both special issues. Most of the work was presented at a workshop on open-ended evolution that was held as a part of the 2018 Conference on Artificial Life in Tokyo, and much of it had antecedents in two previous workshops on open-ended evolution at artificial life conferences in Cancun and York. We present a simplified categorization of OEE and summarize progress in the field as represented by the articles in this special issue.

Open-Ended Evolution and Open-Endedness: Editorial Introduction to the Open-Ended Evolution I Special Issue.

Nature's spectacular inventiveness, reflected in the enormous diversity of form and function displayed by the biosphere, is a feature of life that distinguishes living most strongly from nonliving. It is, therefore, not surprising that this aspect of life should become a central focus of artificial life. We have known since Darwin that the diversity is produced dynamically, through the process of evolution; this has led life's creative productivity to be called Open-Ended Evolution (OEE) in the field. This article introduces the first of two special issues on current research on OEE and on the more general concept of open-endedness. Most of the papers presented in these special issues are elaborations of work presented at the Third Workshop on Open-Ended Evolution, held in Tokyo as part of the 2018 Conference on Artificial Life.

Open-Ended Technological Innovation.

We detect ongoing innovation in empirical data about human technological innovations. Ongoing technological innovation is a form of open-ended evolution, but it occurs in a nonbiological, cultural population that consists of actual technological innovations that exist in the real world. The change over time of this population of innovations seems to be quite open-ended. We take patented inventions as a proxy for technological innovations and mine public patent records for evidence of the ongoing emergence of technological innovations, and we compare two ways to detect it. One way detects the first instances of predefined patent pigeonholes, specifically the technology classes listed in the United States Patent Classification (USPC). The second way embeds patents in a high-dimensional semantic space and detects the emergence of new patent clusters. After analyzing hundreds of years of patent records, both methods detect the emergence of new kinds of technologies, but clusters are much better at detecting innovations that are unanticipated and undetected by USPC pigeonholes. Our clustering methods generalize to detect unanticipated innovations in other evolving populations that generate ongoing streams of digital data.

High-Throughput Optimization Cycle of a Cell-Free Ribosome Assembly and Protein Synthesis System.

Building variant ribosomes offers opportunities to reveal fundamental principles underlying ribosome biogenesis and to make ribosomes with altered properties. However, cell viability limits mutations that can be made to the ribosome. To address this limitation, the in vitro integrated synthesis, assembly and translation (iSAT) method for ribosome construction from the bottom up was recently developed. Unfortunately, iSAT is complex, costly, and laborious to researchers, partially due to the high cost of reaction buffer containing over 20 components. In this study, we develop iSAT in Escherichia coli BL21Rosetta2 cell lysates, a commonly used bacterial strain, with a cost-effective poly sugar and nucleotide monophosphate-based metabolic scheme. We achieved a 10-fold increase in protein yield over our base case with an evolutionary design of experiments approach, screening 490 reaction conditions to optimize the reaction buffer. The computationally guided, cell-free, high-throughput technology presented here augments the way we approach multicomponent synthetic biology projects and efforts to repurpose ribosomes.

Open-Ended Evolution: Perspectives from the OEE Workshop in York.

We describe the content and outcomes of the First Workshop on Open-Ended Evolution: Recent Progress and Future Milestones (OEE1), held during the ECAL 2015 conference at the University of York, UK, in July 2015. We briefly summarize the content of the workshop's talks, and identify the main themes that emerged from the open discussions. Two important conclusions from the discussions are: (1) the idea of pluralism about OEE-it seems clear that there is more than one interesting and important kind of OEE; and (2) the importance of distinguishing observable behavioral hallmarks of systems undergoing OEE from hypothesized underlying mechanisms that explain why a system exhibits those hallmarks. We summarize the different hallmarks and mechanisms discussed during the workshop, and list the specific systems that were highlighted with respect to particular hallmarks and mechanisms. We conclude by identifying some of the most important open research questions about OEE that are apparent in light of the discussions. The York workshop provides a foundation for a follow-up OEE2 workshop taking place at the ALIFE XV conference in Cancún, Mexico, in July 2016. Additional materials from the York workshop, including talk abstracts, presentation slides, and videos of each talk, are available at http://alife.org/ws/oee1 .

A Strategy for Origins of Life Research.

Contents 1. Introduction 1.1. A workshop and this document 1.2. Framing origins of life science 1.2.1. What do we mean by the origins of life (OoL)? 1.2.2. Defining life 1.2.3. How should we characterize approaches to OoL science? 1.2.4. One path to life or many? 2. A Strategy for Origins of Life Research 2.1. Outcomes-key questions and investigations 2.1.1. Domain 1: Theory 2.1.2. Domain 2: Practice 2.1.3. Domain 3: Process 2.1.4. Domain 4: Future studies 2.2. EON Roadmap 2.3. Relationship to NASA Astrobiology Roadmap and Strategy documents and the European AstRoMap Appendix I Appendix II Supplementary Materials References.

A stochastic model of autocatalytic reaction networks.

Autocatalytic cycles are rather widespread in nature and in several theoretical models of catalytic reaction networks their emergence is hypothesized to be inevitable when the network is or becomes sufficiently complex. Nevertheless, the emergence of autocatalytic cycles has been never observed in wet laboratory experiments. Here, we present a novel model of catalytic reaction networks with the explicit goal of filling the gap between theoretical predictions and experimental findings. The model is based on previous study of Kauffman, with new features in the introduction of a stochastic algorithm to describe the dynamics and in the possibility to increase the number of elements and reactions according to the dynamical evolution of the system. Furthermore, the introduction of a temporal threshold allows the detection of cycles even in our context of a stochastic model with asynchronous update. In this study, we describe the model and present results concerning the effect on the overall dynamics of varying (a) the average residence time of the elements in the reactor, (b) both the composition of the firing disk and the concentration of the molecules belonging to it, (c) the composition of the incoming flux.

Coping with complexity: machine learning optimization of cell-free protein synthesis.

Biological systems contain complex metabolic pathways with many nonlinearities and synergies that make them difficult to predict from first principles. Protein synthesis is a canonical example of such a pathway. Here we show how cell-free protein synthesis may be improved through a series of iterated high-throughput experiments guided by a machine-learning algorithm implementing a form of evolutionary design of experiments (Evo-DoE). The algorithm predicts fruitful experiments from statistical models of the previous experimental results, combined with stochastic exploration of the experimental space. The desired experimental response, or evolutionary fitness, was defined as the yield of the target product, and new experimental conditions were discovered to have ∼ 350% greater yield than the standard. An analysis of the best experimental conditions discovered indicates that there are two distinct classes of kinetics, thus showing how our evolutionary design of experiments is capable of significant innovation, as well as gradual improvement.

Measuring the evolution of the drivers of technological innovation in the patent record.

We argue that technology changes over time by an evolutionary process that is similar in important respects to biological evolution. The process is adaptive in the sense that technologies are selected because of their specific adaptive value and not at random, but this adaptive evolutionary process differs from the Darwinian process of random variation followed by natural selection. We find evidence for the adaptive evolution of technology in the US patent record, specifically, the public bibliographic information of all utility patents issued in the United States from 1976 through 2010. Patents record certain innovations in the evolution of technology. The 1976-2010 patent record is huge, containing almost four million patents. We use a patent's incoming citations to measure its impact on subsequent patented innovations. Weighting innovative impact by the dissimilarity between parent and child technologies reveals that many of the most fecund inventions are door-opening technologies that spawn innovations in widely diverse categories.

Leaky membrane dynamics.

A concentration difference of particles across a membrane perforated by pores will induce a diffusive flux. If the diffusing objects are of the same length scale as the pores, diffusion may not be simple; objects can move into the pore in a configuration that requires them to back up in order to continue forward. A configuration that blocks flow through the pore may be statistically preferred, an attracting metastable state of the system. This effect is purely kinetic, and not dependent on potentials, friction, or dissipation. We discuss several geometries which generate this effect, and introduce a heuristic model which captures the qualitative features.

Automated discovery of novel drug formulations using predictive iterated high throughput experimentation.

BACKGROUND: We consider the problem of optimizing a liposomal drug formulation: a complex chemical system with many components (e.g., elements of a lipid library) that interact nonlinearly and synergistically in ways that cannot be predicted from first principles. METHODOLOGY/PRINCIPAL FINDINGS: The optimization criterion in our experiments was the percent encapsulation of a target drug, Amphotericin B, detected experimentally via spectrophotometric assay. Optimization of such a complex system requires strategies that efficiently discover solutions in extremely large volumes of potential experimental space. We have designed and implemented a new strategy of evolutionary design of experiments (Evo-DoE), that efficiently explores high-dimensional spaces by coupling the power of computer and statistical modeling with experimentally measured responses in an iterative loop. CONCLUSIONS: We demonstrate how iterative looping of modeling and experimentation can quickly produce new discoveries with significantly better experimental response, and how such looping can discover the chemical landscape underlying complex chemical systems.

Living technology: exploiting life's principles in technology.

The concept of living technology-that is, technology that is based on the powerful core features of life-is explained and illustrated with examples from artificial life software, reconfigurable and evolvable hardware, autonomously self-reproducing robots, chemical protocells, and hybrid electronic-chemical systems. We define primary (secondary) living technology according as key material components and core systems are not (are) derived from living organisms. Primary living technology is currently emerging, distinctive, and potentially powerful, motivating this review. We trace living technology's connections with artificial life (soft, hard, and wet), synthetic biology (top-down and bottom-up), and the convergence of nano-, bio-, information, and cognitive (NBIC) technologies. We end with a brief look at the social and ethical questions generated by the prospect of living technology.

Fatty acid chemistry at the oil-water interface: self-propelled oil droplets.

Fatty acids have been investigated as boundary structures to construct artificial cells due to their dynamic properties and phase transitions. Here we have explored the possibility that fatty acid systems also demonstrate movement. An oil phase was loaded with a fatty acid anhydride precursor and introduced to an aqueous fatty acid micelle solution. The oil droplets showed autonomous, sustained movement through the aqueous media. Internal convection created a positive feedback loop, and the movement of the oil droplet was sustained as convection drove fresh precursor to the surface to become hydrolyzed. As the system progressed, more surfactant was produced and some of the oil droplets transformed into supramolecular aggregates resembling multilamellar vesicles. The oil droplets also moved directionally within chemical gradients and exhibited a type of chemotaxis.

Evolutionary self-organization in complex fluids.

This paper explores the ability of molecular evolution to take control of collective physical phases, making the first decisive step from independent replicators towards cell-like collective structures. We develop a physical model of replicating combinatorial molecules in a ternary fluid of hydrocarbons, amphiphiles and water. Such systems are being studied experimentally in various laboratories to approach the synthesis of artificial cells, and are also relevant to the origin of cellular life. The model represents amphiphiles by spins on a lattice (with Ising coupling in the simplest case), coupled to replicating molecules that may diffuse on the lattice and react with each other. The presence of the replicating molecules locally modulates the phases of the complex fluid, and the physical replication process and/or mobility of the replicating molecules is influenced by the local amphiphilic configuration through an energetic coupling. Consequently, the replicators can potentially modify their environment to enhance their own replication. Through this coupling, the system can associate hereditary properties, and the potential for autonomous evolution, to self-assembling mesoscale structures in the complex fluid. This opens a route to analyse the evolution of artificial cells. The models are studied using Monte Carlo simulation, and demonstrate the evolution of phase control. We achieve a unified combinatorial framework for the description of isotropic families of spin-lattice models of complex phases, opening up the physical study of their evolution.

Geometry-induced asymmetric diffusion.

Past work has shown that ions can pass through a membrane more readily in one direction than the other. We demonstrate here in a model and an experiment that for a mixture of small and large particles such asymmetric diffusion can arise solely from an asymmetry in the geometry of the pores of the membrane. Our deterministic simulation considers a two-dimensional gas of elastic disks of two sizes diffusing through a membrane, and our laboratory experiment examines the diffusion of glass beads of two sizes through a metal membrane. In both experiment and simulation, the membrane is permeable only to the smaller particles, and the asymmetric pores lead to an asymmetry in the diffusion rates of these particles. The presence of even a small percentage of large particles can clog a membrane, preventing passage of the small particles in one direction while permitting free flow of the small particles in the other direction. The purely geometric kinetic constraints may play a role in common biological contexts such as membrane ion channels.

Topology and evolution of technology innovation networks.

The web of relations linking technological innovation can be fairly described in terms of patent citations. The resulting patent citation network provides a picture of the large-scale organization of innovations and its time evolution. Here we study the patterns of change of patents registered by the U.S. Patent and Trademark Office. We show that the scaling behavior exhibited by this network is consistent with a preferential attachment mechanism together with a Weibull-shaped aging term. Such an attachment kernel is shared by scientific citation networks, thus indicating a universal type of mechanism linking ideas and designs and their evolution. The implications for evolutionary theory of innovation are discussed.

Evolution of evolvability via adaptation of mutation rates.

We examine a simple form of the evolution of evolvability-the evolution of mutation rates-in a simple model system. The system is composed of many agents moving, reproducing, and dying in a two-dimensional resource-limited world. We first examine various macroscopic quantities (three types of genetic diversity, a measure of population fitness, and a measure of evolutionary activity) as a function of fixed mutation rates. The results suggest that (i) mutation rate is a control parameter that governs a transition between two qualitatively different phases of evolution, an ordered phase characterized by punctuated equilibria of diversity, and a disordered phase of characterized by noisy fluctuations around an equilibrium diversity, and (ii) the ability of evolution to create adaptive structure is maximized when the mutation rate is just below the transition between these two phases of evolution. We hypothesize that this transition occurs when the demands for evolutionary memory and evolutionary novelty are typically balanced. We next allow the mutation rate itself to evolve, and we observe that evolving mutation rates adapt to values at this transition. Furthermore, the mutation rates adapt up (or down) as the evolutionary demands for novelty (or memory) increase, thus supporting the balance hypothesis.