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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

While Mind Over Matter reviews new abilities to fathom and restart an animate physical creation, Second Genesis will here report and document similar natural palliative and positive genetic and biological capabilities. At the outset as these potentials suddenly open and beckon we cite ethical concerns, more so throughout this site, which need play a guiding role. As evolution may finally reach its emergent term of geonatal (cosmonatal) self-cognizance, our collective, sapient knowledge can help mitigate, revise, and enhance life’s genotype source and phenotype cellular beingness. Life’s long, arduous contingent phase, a cobbled, tinkered, brutal yet an oriented development, might at last reach its intended curative and creative resolve and fulfillment. A Second Genesis phrase is proffered as distinguished by a successful passage of the parental cosmome bigender endowment to our future kinderkind edification.

2020: While Mind/Matter above was about a conducive substantiality, this section surveys how our Earthomo MindKinder is achieving similar understandings and abilities to take up and over life’s prior trial and error contingency in an intentional, directed and respectful way. As the entries convey, all manner of cellular, metabolic, network anatomy and physiology can be healed and enhanced. A prime breakthrough is the editing ease of CRISPR genetics. Beyond this, new ways to expand and rewrite life’s genomic source code seem to be patentially passing, as intended, to our wumanwise futurity.

Once again, as for each section there is a vast, multifaceted bibliography in this intense endeavor as life begins to make itself wholly over in an informed, directed, evolition. Here is a small sampling.

Bekiaris, Pavlos and Steffen Klamt. Designing Microbial Communities to Maximize the Thermodynamic Driving Force for the Production of Chemicals. PLoS Computational Biology. June, 2021.
Bianco, Simone, et al. Towards Computer-aided Design of Cellular Structure. Physical Biology. 17/2, 2020.
Cable, Jennifer, et al. Synthetic Biology: At the Crossroads of Genetic Engineering and Human Therapeutics. Annals of the New York Academy of Sciences. November, 2021.
Davies, Jamie. Real-World Synthetic Biology. Life. 9/1, 2019.
De la Torre, Daniel and Jason Chin. Reprogramming the Genetic Code. Nature Reviews Genetics. 22/3, 2021.
Hernandez-Espinosa, Nancy, et al. Stimulus-responsive Self-assembly of Protein-based Fractals by Computational Design. Nature Chemistry. 11/7, 2019.

Lale, Rahmi, et al. A Universal Approach to Gene Expression Engineering. Synthetic Biology. 7/1, 2022.
Ostrov, Nili, et al. Synthetic Genomes with Altered Genetic Codes. Current Opinion in Systems Biology. October 2020.
Qiu, Yuchi, et al. Cluster Learning-Assisted Directed Evolution. Nature Computational Science. December, 2021
Scalise, Dominic and Rebecca Shulman. Controlling Matter at the Molecular Scale with DNA Circuits. Annual Review of Biomedical Engineering. 21/469, 2019.
Vidiella, Blai, et al. Engineering Self-Organized Criticality in Living Cells. Nature Communications. I12/4415, 2021
Yilmaz, Suzzan, et al. Towards Next-Generation Cell Factories by Rational Geome-Scale Engineering Nature Catalysis. 5/9, 2022
Vibhute, Mahesh and Hannes Mutschler. A Primer on Building Life-Like Systems. ChemSystemsChem. December, 2022

2023:

FLinT Center for Fundamental Living Technology. flint.sdu.dk. A University of Southern Denmark group led by Steen Rasmussen (search), Pierre-Alain Monnard (search), and Carsten Svaneborg. The Science Advisory Board is made up of Mark Bedau, David Deamer, John McCaskill, and Norman Packard, who are leading researchers in this fledgling endeavor of cosmic biomimetics.

Our scientific mission is to analyze and understand the creative forces in natural- as well as in human-made systems. This is mainly done through the study of self-organizing processes. Our main focus is to assemble the components of minimal living systems. In physico-chemical systems this means assembling protocells bottom up from inorganinc and organic materials. In hardware systems we investigate implementation of e.g. 3D printers able to print themselves, while in computational systems we study the emergence of replicators. Our long-term technological vision is to develop the foundation for a living technology characterized by robustness, autonomy, energy efficiency, sustainability, local intelligence, self-repair, adaptation, self-replication and evolution, all properties current technology lack, but living systems possess.

Genome Engineering: Cutting-Edge Research and Applications. www.faseb.org/src/micro/Site/GenEng/Home.aspx. A mid June 2016 international conference sponsored by the Federation of American Society for Experimental Biology FASEB at the Lisbon Marriott Hotel, Portugal. The main keynote speaker is Emmanuelle Charpentier, the co-conceiver with Jennifer Doudna of CRISPR genome editing, and now director of the MPI for Infection Biology. The array of sessions and talks are all about this plethora of novel, inviting technologies that have opened for human, social, and environmental avail. Typical papers are Programming the Third Genome through Mitochondrial DNA Editing by Stephen Ekker (Mayo Clinic), The Genome Engineering Revolution and Plant Agriculture by Dan Voytas (University of Minnesota), and Epigenome Editing with ZFP and CRISPR by Qingzhou (Millipore Sigma).

Genome engineering is a rapidly growing discipline that seeks to develop new technologies for the precise manipulation of genes and genomes in cellula and in vivo. In addition to its utility for advancing our understanding of basic biology, genome engineering has numerous real-world applications, ranging from correction of disease-causing mutations in humans to engineering plants that better provide fuel, food and industrial raw materials. The first clinical trials and patient treatments using genome engineering approaches are now a reality. The scope of this meeting is expansive, encompassing multiple approaches for modifying genomes – from transgenesis and gene targeting to the creation of synthetic genomes. The experimental models featured include bacteria, fungi, model organisms (e.g.—Drosophila, C. elegans, zebrafish, mice, rats), plants, humans, and animals including livestock. We anticipate that this diversity of approaches and experimental systems will create a stimulating meeting environment that will enable new insights and advance the field.

Oxford Nanopore Technologies Limited. nanoporetech.com. This is a British company in Oxford Science Park since 2005 at the frontiers of public, beneficial genetic capabilities. An article A Genome in the Hand in The Economist (Dec. 9, 2017) cites their MinION device as a low cost, useable way of personal DNA sequencing which, for example, now serves medics in rural Africa. A Publications icon connects with technical papers such as Efficient Generation of Complete Sequences of MDR-encoding Plasmids and Automated Eukaryotic Genome Annotation based on Long-Read cDNA Sequencing.

Aguade-Gorgoio, G., et al. An Oncospace for Human Cancers. Preprints.org. November, 2022. Barcelona biosystem theorists including Ricard Sole propose ways situate this major malady in an ecological, evolutionary, developmental, genetic and metabolic expanse so to gain more appropriate understandings and therapies. Box 1 is Morphogenesis: The Geometry of Biological Complexity. In effect, into the 2020s a much wider and deeper holistic, integrative approach and medicine promises a new frontier on its cause and eradication. In this temporal vista, a worldwise knowledge repository accures by which emergent life, mind and self can feedback to heal and cure the fraught being from whom it arose.

Human cancers comprise an heterogeneous array of diseases with different progression patterns and treatment responses. However, they all develop within a host context that constraints their natural history. Is there a way to capture the broad range of tumor types within a space of the possible? Here we define the oncospace, a coordinate system that integrates the ecological, evolutionary and developmental components. We postulate that the oncospace topology encodes new information regarding tumorigenic pathways, subtype prognosis and therapeutic opportunities.

Aktipis, Athena et al. Cancer across the Tree of Life: Cooperation and Cheating in Multicellularity. Philosophical Transactions of the Royal Society B. 370/Issue 1673, 2015. A lead article by UC San Francisco, University of Kiel, University of Montpellier, and University of Maryland researchers about advances in the study and resolve of this disease by way of complex systems science and the major transitions paradigm. These evolutionary and life history expansions, not possible much earlier, achieve a novel mathematical theory and natural basis for this virulent cellular aberration. Some papers are Infection and Cancer in Multicellular Organisms by Paul and Holly Ewald, and Comparative Oncology: What Dogs and Other Species can Teach us about Humans with Cancer by Joshua Schiffman and Matthew Breen. In retrospect, a worldwide palliative knowledge emerges which can be fed back to succor and cure the fraught beings it arose from. What kind of a genesis cosmos can learn and proceed, via a human phenomenon, to cure itself so as take over its future creation?

Multicellularity is characterized by cooperation among cells for the development, maintenance and reproduction of the multicellular organism. Cancer can be viewed as cheating within this cooperative multicellular system. Complex multicellularity, and the cooperation underlying it, has evolved independently multiple times. We review the existing literature on cancer and cancer-like phenomena across life, not only focusing on complex multicellularity but also reviewing cancer-like phenomena across the tree of life more broadly. We find that cancer is characterized by a breakdown of the central features of cooperation that characterize multicellularity, including cheating in proliferation inhibition, cell death, division of labour, resource allocation and extracellular environment maintenance (which we term the five foundations of multicellularity). Cheating on division of labour, exhibited by a lack of differentiation and disorganized cell masses, has been observed in all forms of multicellularity. This suggests that deregulation of differentiation is a fundamental and universal aspect of carcinogenesis that may be underappreciated in cancer biology. Understanding cancer as a breakdown of multicellular cooperation provides novel insights into cancer hallmarks and suggests a set of assays and biomarkers that can be applied across species and characterize the fundamental requirements for generating a cancer. (Abstract)

Alfonzo, E., et al. New additions to the arsenal of biocatalysts for noncanonical amino acid synthesis. Current Opinion Green Sustainable Chemistry. December, 2022. Cal Tech researchers including Nobel laureate Frances Arnold at once advance these biochemical capabilities and cite their therapeutic and palliative value from new medicines to pandemics.

Noncanonical amino acids (ncAAs) merge the conformational behavior and native interactions of proteinogenic amino acids with nonnative chemical motifs and have proven invaluable in developing modern therapeutics. This blending of native and nonnative characteristics has resulted in essential drugs like nirmatrelvir, which comprises three ncAAs and is used to treat COVID-19. Abiotic enzyme-catalyzed reactions exploit the selectivity afforded by a macromolecular catalyst to access molecules not available to natural enzymes and perhaps not even chemical catalysis. (Excerpt)

Evolution, Synthetic Biology, Protein Engineering, Biocatalysis, Biofuels. www.che.caltech.edu/groups/fha. The website for the Frances H. Arnold (Chemical Engineering) Research Group at the California Institute of Technology. A good example of the use of evolutionary principles and algorithms to achieve novel biomolecular entities of service to society in many areas, as the title conveys. I have recently heard Prof. Arnold speak at Smith College, and upon reflection, one gets the impression of material and biological creation passing to conscious, intentional human facilitation. (If the URL does not work, just Google her name.)

Arranz-Gilbert, Pol, et al. Next-Generation Genetic Code Expansion. Current Opinion in Chemical Biology. 46/1, 2018. Yale University biogeneticists associated with Mark Gerstein and Gunter Wagner scope out new abilities to modify, edit, rewrite, and expand so to carefully finesse “Genomically Recoded Organisms” (GROs). In a Synthetic Biology section, see also Expansion of the Genetic Code via the Genetic Alphabet by Vivian Dien, et al, and Synthetic Darwinism and the Aperiodic Crystal Structure by Nilesh Karalkar and Steven Benner (below).

Engineering of the translation apparatus has permitted the site-specific incorporation of nonstandard amino acids (nsAAs) into proteins, thereby expanding the genetic code of organisms. Conventional approaches have focused on porting tRNAs and aminoacyl-tRNA synthetases (aaRS) from archaea into bacterial and eukaryotic systems where they have been engineered to site-specifically encode nsAAs. These advances, together with the advent of engineered ribosomes and new molecular evolution methods, enable multisite incorporation of nsAAs and nonstandard monomers (nsM) paving the way for the template-directed production of functionalized proteins, new classes of polymers, and genetically encoded materials. (Abstract)

Baker, Monya. The Next Step for the Synthetic Genome. Nature. 473/403, 2011. The technology editor reports upon a pregnant age of human potentials to make genetic and biological life all over again. What manner of cosmos then after billions of years evolves we such beings able to “read and write” their own DNA code so as to continue creation in a radically intentional way?

Bates, Maxwell, et al. Genetic Constructor: An Online DNA Design Platform. ACS Synthetic Biology. Online October 12, 2017. We cite this paper by a dozen researchers from Autodesk Life Sciences, San Francisco, University of Edinburgh, and Radiant Genomics, Emeryville, CA to notice and report the extent to which a global human intellect is advancing and expanding this broadly conceived naturome literacy as a basis for a new intentional procreation.

Genetic Constructor is a cloud Computer Aided Design (CAD) application developed to support synthetic biologists from design intent through DNA fabrication and experiment iteration. The platform allows users to design, manage, and navigate complex DNA constructs and libraries, using a new visual language that focuses on functional parts abstracted from sequence. Features like combinatorial libraries and automated primer design allow the user to separate design from construction by focusing on functional intent, and design constraints aid iterative refinement of designs. Genetic Constructor seeks to democratize DNA design, manufacture, and access to tools and services from the synthetic biology community. (Abstract)

Bedau, Mark and Emily Parke, eds. The Ethics of Protocells. Cambridge: MIT Press, 2009. Reviewed more in The Origin of Life, what to do about this instant ability to bring about a new creation.

Bedau, Mark, et al. Introduction to Recent Developments in Living Technology. Artificial Life. 19/3-4, 2013. With John McCaskill, Norman Packard, Emily Parke and Steen Rasmussen, a special issue to update and expand this American and European project with a Santa Fe Institute – University of Southern Denmark nexus to intentionally re-imagine a humane abidance much more life, creature, socially, and environmentally healthy. In regard, throughout the writings a respectful sense of cultural and ethical implications abides. See for example “Living in Living Cities” by Carlos Gershenson, and “Bespoke Physics for Living Technology” by David Ackley.

In the physics of the natural world, basic tasks of life, such as homeostasis and reproduction, are extremely complex operations, requiring the coordination of billions of atoms even in simple cases. By contrast, artificial living organisms can be implemented in computers using relatively few bits, and copying a data structure is trivial. Of course, the physical overheads of the computers themselves are huge, but since their programmability allows digital “laws of physics” to be tailored like a custom suit, deploying living technology atop an engineered computational substrate might be as or more effective than building directly on the natural laws of physics, for a substantial range of desirable purposes. This article suggests basic criteria and metrics for bespoke physics computing architectures, describes one such architecture, and offers data and illustrations of custom living technology competing to reproduce while collaborating on an externally useful computation. (Ackley Abstract)

This article presents an overview of current and potential applications of living technology to some urban problems. Living technology can be described as technology that exhibits the core features of living systems. These features can be useful to solve dynamic problems. In particular, urban problems concerning mobility, logistics, telecommunications, governance, safety, sustainability, and society and culture are presented, and solutions involving living technology are reviewed. A methodology for developing living technology is mentioned, and supraoptimal public transportation systems are used as a case study to illustrate the benefits of urban living technology. Finally, the usefulness of describing cities as living systems is discussed. (Gershenson Abstract)

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