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A Sourcebook for the Worldwide Discovery of a Creative Organic Universe
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VIII. Earth Earns: An Open Participatory Earthropocene to Astropocene CoCreative Future

2. Second Genesis: Sentient LifeKinder Transitions to a New Intentional, BioGenetic Questiny

Design, Jai and Chaitanya Gokhale.. Synthetic Mutualism and the Intervention Dilemma. Life. 9/1, 2019. Okinawa Institute of Science and Technology, Genomics and Regulatory Systems Unit, and MPI Evolutionary Biology, Theoretical Models of Eco-Evolutionary Dynamics Group researchers extend this nascent endeavor to both gain a better understanding of how life has naturally evolved, developed and emerged, and how our human sapience might begin a intentional procreation by respectful, informed continuance. A working phrase herein is a Synthetic Symbiosis, which could also inspire better human communities.

Ecosystems are complex networks of interacting individuals co-evolving with their environment. As such, changes to an interaction can influence the whole ecosystem. However, to predict the outcome of these changes, considerable understanding of processes driving the system is required. Synthetic biology provides tools to aid this understanding, which then may allow us to change specific interactions. Of particular interest is the ecological importance of mutualism, a subset of cooperative interactions. Mutualism occurs when individuals of different species provide a reciprocal fitness benefit. We review available experimental techniques from the stability of microbial communities in extreme environments to the collapse of ecosystems due to high levels of human intervention. We evaluate the promise of synthetic biology by way of ethics and laws regarding biological alterations, whether on Earth or beyond. (Abstract excerpt)

Dien, Vivian, et al. Progress Toward a Semi-Synthetic Organism with an Unrestricted Expanded Genetic Alphabet. Journal of the American Chemical Society. 140/47, 2018. A six person team from Floyd Romesberg’s laboratory at the Scripps Research Institute, La Jolla, CA describe a highly technical exercise by which to begin modifications and enhancements of life’s original four letter genomic code. The work was noted in the popular press as Life, Rewritten by James Crow (New Scientist, Dec. 8, 2018), see also the Biondi and Benner entry above.

We have developed a family of unnatural base pairs (UBPs), exemplified by the pair formed between dNaM and dTPT3, for which pairing is mediated not by complementary hydrogen bonding but by hydrophobic and packing forces. These UBPs enabled the creation of the first semisynthetic organisms (SSOs) that store increased genetic information and use it to produce proteins containing noncanonical amino acids. The results demonstrate the importance of evaluating synthetic biology “parts” in their in vivo context and the ability of hydrophobic and packing interactions to replace the complementary hydrogen bonding that underlies the replication of natural base pairs. The identification of dMTMO-dTPT3 and especially dPTMO-dTPT3 represents significant progress toward the development of SSOs able to store and retrieve increased information. (Abstract excerpt)

Doursat, Rene, et al. Morphogenetic Engineering: Toward Programmable Complex Systems. Berlin: Springer, 2013. Rene Doursat, CNRS and Ecole Polytechnique, Paris, with Olivier Michel, Universite Paris, and Hiroki Sayama, Binghamton SUNY, and colleagues gather a volume to propose both novel understandings of life’s self-organizing evolutionary embryogenesis, so as to then intentionally apply these natural principles for recreating a better, more livable world. In regard, organic aspects such as nanomaterial, medical, agricultural, urban system domains receive specific treatment. The editor’s introductory chapter is “Morphogenetic Engineering: Reconciling Self-Organization and Architecture,” Other contributions are “Programming Self-Assembling Systems via Physically Encoded Information” by Navneet Bhalla and Peter Bentley and “Embryomorphic Engineering: Emergent Innovation Through Evolutionary Development” by Rene Doursat, et al. As the Abstracts next convey, it is worth notice that an inherent generative spontaneity is seen at work in life’s nonlinear emergence, which is evidentially traced to and rooted in conducive physical and chemical substrates.

Generally, phenomena of spontaneous pattern formation are random and repetitive, whereas elaborate devices are the deterministic product of human design. Yet, biological organisms and collective insect constructions are exceptional examples of complex systems that are both architectured and self-organized. Can we understand their precise self-formation capabilities and integrate them with technological planning? Can physical systems be endowed with information, or informational systems be embedded in physics, to create autonomous morphologies and functions? This book is the first initiative of its kind toward establishing a new field of research, Morphogenetic Engineering, to explore the modeling and implementation of “self-architecturing” systems. Particular emphasis is set on the programmability and computational abilities of self-organization, properties that are often underappreciated in complex systems science—while, conversely, the benefits of self-organization are often underappreciated in engineering methodologies. (Introduction Abstract)

Throughout nature, in both the inorganic and organic realms, complex entities emerge as a result of self-assembly from decentralised components governed by simple rules. Natural self-assembly is dictated by the morphology of the components and the environmental conditions they are subjected to, as well as the physical and chemical properties of their components and environments—their information. Components, their environment, and the interactions among them form a system, which can be described as a set of simple rules. The process of self-assembly is equivalent to a physical computation, through the interaction and transformation of physically and chemically encoded information. (Bhalla, Bentley Abstract)

Embryomorphic Engineering, a particular instance of Morphogenetic Engineering, takes its inspiration directly from biological development to create new robotic, software or network architectures by decentralized self-assembly of elementary agents. At its core, it combines three key principles of multicellular embryogenesis: chemical gradient diffusion (providing positional information to the agents), gene regulatory networks (triggering their differentiation into types, thus patterning), and cell division or aggregation (creating structural constraints, thus reshaping). In all cases, the specific genotype shared by all the agents makes the phenotype’s complex architecture and function modular, programmable and reproducible. (Doursat, et al, Abstract)

Draxler, Breanna. Life as We Grow It. Discover Magazine. October, 2013. An extensive report upon the potentials and perils of “Synthetic Biology,” as auspicious abilities to make over everything and everyone burst upon us. To get a handle and march on it, the magazine convened in July at UC Berkeley, aided by the Synberc consortium, scientists and ethicists George Church, Douglas Densmore, Drew Endy, Steve Evans, Jay Keasling, Christina Smolke, Virginia Ursin, Christopher Voigt, and Laurie Zoloth, along with futurist Juan Enriquez. Topical sections are Evolution by Design, Biology Reimagined, Designing Living Solutions, Programming Life, Replacing Petroleum, Promises and Implications, for which we need a tandem advance of monitored research with respectful considerations. But may one wonder what kind of an unfinished cosmos, by virtue of an emergent collective knowledge, then proceeds to cure, heal, correct, remake, improve, immortalize, the contingent fish on feet persons from which it arose?

Dyson, Freeman. Our Biotech Future. New York Review of Books. July 19, 2007. Our octogenarian Renaissance person surveys the entirety of past, present and future genetic evolution. Drawing on the biological wisdom of Carl Woese, who avers that life is not a machine but graced by dynamic organization, three phases can now be seen. When replicating molecules first appeared in ancient protocells, gene transfer was ‘horizontal’ in kind taking place readily across these prokaryotic vesicles. As nucleated cells and multicellular organisms arose, the Darwinian mode of ‘vertical’ asexual and sexual transfer proceeded until this day. With the advent of potent biotechnological capacities, a third phase is dawning which might again take to the sideways course. Dyson contends that much palliative benefit could result from its careful, sustainable implementation. An example cited is a recovery of village agriculture via appropriately modified crops in many lands of Africa and the Asian subcontinent, which would help reverse the flight to fetid mega-cities.

Egbert, Robert and Eric Klavins. Fine-Tuning Gene Networks using Simple Sequence Repeats. Proceedings of the National Academy of Sciences. 109/16817, 2012. University of Washington bioengineers develop effective methods for tweaking gene expression or harmony by way of “variable-length repeating DNA spacers.” In the same issue is a review “Making Gene Circuits Sing” by Arthur Prindle and Jeff Hasty. Who are we peoples to lately appear and be able to take up such editing and orchestrating of nature’s procreative genotype code?

The parameters in a complex synthetic gene network must be extensively tuned before the network functions as designed. Here, we introduce a simple and general approach to rapidly tune gene networks in Escherichia coli using hypermutable simple sequence repeats embedded in the spacer region of the ribosome binding site. By varying repeat length, we generated expression libraries that incrementally and predictably sample gene expression levels over a 1,000-fold range. We demonstrate the utility of the approach by creating a bistable switch library that programmatically samples the expression space to balance the two states of the switch, and we illustrate the need for tuning by showing that the switch’s behavior is sensitive to host context. Further, we show that mutation rates of the repeats are controllable in vivo for stability or for targeted mutagenesis—suggesting a new approach to optimizing gene networks via directed evolution. This tuning methodology should accelerate the process of engineering functionally complex gene networks. (Abstract)

Elani, Yuval and John M. Seddon. What it means to be alive: a synthetic cell perspective. Interface Focus. August, 2023. An introduction to papers from a R0yal S0ciety November 2022 symposium about Cell mimicry: bottom-up engineering of life.’ An initial entry by Stephen Mann with this title well scopes out the many potentials of these novel abilities going forward. Some other papers are On biochemical constructors and synthetic cells by Sebastian Maerkl and DNA droplets for intelligent and dynamical artificial cells: from the viewpoint of computation and non-equilibrium systems by Masahiro Takinoue.

Advances in bottom-up synthetic biology offer the exciting—albeit contentious—prospect of transitioning bio-science researchers from passive observers of life to potential creators of it. Synthetic cells closely emulate the attributes of their biological counterparts. These rationally designed microsystems exhibit emergent properties and life-like functionalities. They can therefore be used as simplified cell models to decipher the rules of life, and as programmable biologically powered micromachines for application in healthcare and biotechnology more broadly. (Elani and Seddon)

Emani, Prashant, et al. Quantum Computing at the Frontiers of Biological Sciences. arXiv:1911.07127. Eighteen system geneticists from across the USA and onto the UK, including Marc Gerstein and Alan Aspuru-Guzik, scope out how the latest informational processing abilities by the unique properties of this physical realm can foster a new speedy phase of decipherment, discovery and biocreativity. Case examples are then drawn from an organismic span of genomes (GWAS) to cells, organic systems, brains, consequent behaviors and onto integrations across disciplines.

The search for meaningful structure in biological data is aided by advances in computational technology and data science. However, challenges arise as we push the limits of scale and complexity in biological problems. Classical computing hardware and algorithms continue to progress, but new paradigms to circumvent current barriers to processing speed are needed. Here we seek to innovate quantum computation and quantum information methods with polynomial and exponential speedups by way of machine learning. In regard, we explore the potential for quantum computing to aid in the merging of insights from genetics, genomics, neuroimaging and behavioral phenotyping. We highlight the need for a common language between biological data analysis and quantum computing algorithms across the biological sciences. (Abstract excerpt)

Erlich, Yaniv and Dina Zielinski. DNA Fountain Enables a Robust and Efficient Storage Architecture. Science. 355/950, 2017. New York Genome Center, Columbia University, bioinformatic geneticists achieve a novel method by which to better access the extraordinary ability of nucleotide molecules to store vast amounts of digital data.

DNA has the potential to provide large-capacity information storage. However, current methods have only been able to use a fraction of the theoretical maximum. Erlich and Zielinski present a method, DNA Fountain, which approaches the theoretical maximum for information stored per nucleotide. They demonstrated efficient encoding of information—including a full computer operating system—into DNA that could be retrieved at scale after multiple rounds of polymerase chain reaction. (Editor)

Falk, Johannes , et al. Context in Synthetic Biology. Journal of Chemical Physics. 180/024106, 2019. Technical University of Dormstadt biophysicists including Barbara Drossel scope out ways to intentionally carry forth the latest complexity theories so we can proceed to make Earth life better. It might also be noted that a 2001 paper, Biological Evolution and Statistical Physics, by B. Drossel in Advances in Physics (50/2) was one of the first of its integrative kind in a physics journal (second quote) which can show how far and fast this global project has grown and advanced.

Synthetic biology aims at designing modular genetic circuits that can be assembled according to the desired function. When embedded in a cell, a circuit module becomes a small subnetwork within a larger environmental network, and its dynamics is therefore affected by potentially unknown interactions with the environment. It is well-known that the presence of the environment not only causes extrinsic noise but also memory effects, which means that the dynamics of the subnetwork is affected by its past states via a memory function that is characteristic of the environment. We study several generic scenarios for the coupling between a small module and a larger environment, with the environment consisting of a chain of mono-molecular reactions. By mapping the dynamics of this coupled system onto random walks, we are able to give exact analytical expressions for the arising memory functions. Hence, our results give insights into the possible types of memory functions and thereby help to better predict subnetwork dynamics. (Falk Abstract)

This review is an introduction to theoretical models and mathematical calculations for biological evolution, aimed at physicists. The methods in the field are naturally very similar to those used in statistical physics, although the majority of publications have appeared in biology journals. The review has three parts, which can be read independently. The first part deals with evolution in fitness landscapes and includes Fisher's theorem, adaptive walks, quasispecies models, effects of finite population sizes, and neutral evolution. The second part studies models of coevolution, including evolutionary game theory, kin selection, group selection, sexual selection, speciation, and coevolution of hosts and parasites. The third part discusses models for networks of interacting species and their extinction avalanches. (Drossel 2001 Abstract)

Feldman, Aaron and Floyd Romesberg. Expansion of the Genetic Alphabet: A Chemist’s Approach to Synthetic Biology. Accounts of Chemical Research. Online December, 2017. In a breakthrough paper which achieved much press coverage, senior Scripps Research Institute chemists describe capabilities by which to commence an edit and rewrite of nature’s original four letter code. And if to wax about it , over some 13.8 billion cosmic years and 4 billion Earth years, life’s evolutionary emergence just now reaches our moment of intentional humankinder continuance for all futures. In regard, human beings may gain an apparent identity, which we need realize by ourselves, in some way as procreative bigender genomes. What am I trying to say – here is an example of a salutary discovery and destiny for human and universe in our midst for the asking and witness.

Flani, Yuval and John M. Seddon. ‘Cell mimicry: bottom-up engineering of life’. Interface Focus. August, 2023. A special issue of papers from a November 2022 Royal Society Scientific Discussion Meeting on this topical frontier. A lead article by Stephen Mann sets the scenic vjsta, followed by On biochemical constructors and synthetic cells by sebastian Maerkl, DNA droplets for intelligent and dynamical artificial cells: from the viewpoint of computation and non-equilibrium systems by Masahiro Takinoue and so on.

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