VII. Pedia Sapiens: A Genesis Future on Earth and in the Heavens

2. A Second Genesis: Life Begins Anew via an EarthWise Respectful Creativity

Knox, Margaret. The Genie Gene. Scientific American. December, 2014. A popular report on the discovery by Jennifer Doudna, UC Berkeley and Emmanuelle Carpentier, Umea University, Sweden of a revolutionary way to easily alter and edit genetic material. Known as CRISPR for “clustered, regularly interspaced, short palindromic repeats,” it mimics how bacteria employ immune defenses. The innovative research has won prizes, large grants, and is seen as a breakthrough medical advance.

Krane, Dan and Michael Raymer. Fundamental Concepts of Bioinformatics. San Francisco: Benjamin Cummings, 2003. A general introductory text for this merger of computers and biology.

Lajoie, Marc, et al. Overcoming Challenges in Engineering the Genetic Code. Journal of Molecular Biology. 428/5B, 2016. Harvard Medical School and Yale University systems geneticists including George Church consider issues and concerns such as do we really know what we are doing, how and why to carefully proceed, and so on. And as someone who had a day job for decades as an engineer, this term is quite inapt for such genomic, biological, organismic mediations going forward. What better word might serve our own “evolutionary” narrative so as to begin, as we are meant to do, a new genesis recreation?

Withstanding 3.5 billion years of genetic drift, the canonical genetic code remains such a fundamental foundation for the complexity of life that it is highly conserved across all three phylogenetic domains. Genome engineering technologies are now making it possible to rationally change the genetic code, offering resistance to viruses, genetic isolation from horizontal gene transfer, and prevention of environmental escape by genetically modified organisms. We discuss the biochemical, genetic, and technological challenges that must be overcome in order to engineer the genetic code. (Abstract)

Lau, Yu Heng, et al. Large-Scale Recoding of a Bacterial Genome by Iterative Recombineering of Synthetic DNA. Nucleic Acids Research. 45/11, 2017. As the quote notes, a 13 person team from colleges and companies including Jeffrey Way, Pamela Silver, and Elena Schafer, move beyond gene sequencing onto initial surveys of how to edit, reconceive, and expand the generative capacities of nucleotide systems. But “engineering” is an inappropriate, off-putting term. Rather as humankinder altogether begins to engage, decipher, and modify evolution’s original genetic literacy, as it seems we are meant to do, a better image might be as creative co-authors and curators as we learn to read and write this natural language.

The ability to rewrite large stretches of genomic DNA enables the creation of new organisms with customized functions. However, few methods currently exist for accumulating such widespread genomic changes in a single organism. In this study, we demonstrate a rapid approach for rewriting bacterial genomes with modified synthetic DNA. (Abstract) The next widely anticipated breakthrough in genetic engineering is the ability to rapidly rewrite the genomes of industrially relevant microbes, plants, and animals. Rewriting entire genomes will deepen our understanding of the genetic code and dramatically transform human health, food and energy production, and our environment. A major challenge identified by the Genome Project-Write consortium is the efficiency of building and testing large modified genomes. (1)

Lawson, Christopher, et al. Common Principles and Best Practices for Engineering Microbiomes. Nature Reviews Microbiology. 17/725, 2019. In a Tractability and Translation section, a thirteen member team from the Universities of Wisconsin, Montana, Tennessee, Minnesota, Purdue, UC Santa Barbara, Michigan, Delft, and Lawrence Berkeley Labs scope out procedures as our composite human intellect begins to manage and make anew our microbial inhabitants. Some are symbiotic, but others are viral invasive. Thus, an historic phase of palliative and beneficial apply, with all due respects, is in commencement. See also Scientists’ Warning to Humanity: Microorganisms and Climate Change by Ricardo Cavicchioli, et al in this journal (June 18, 2019).

In a Tractability and Translation section, a thirteen member team from the Universities of Wisconsin, Montana, Tennessee, Minnesota, Purdue, UC Santa Barbara, Michigan, Delft, and Lawrence Berkeley Labs scope out procedures as our composite human intellect begins to manage and make anew our microbial inhabitants. Some are symbiotic, but others are viral invasive. Thus, an historic phase of palliative and beneficial apply, with all due respects, is in commencement. See also Scientists’ Warning to Humanity: Microorganisms and Climate Change by Ricardo Cavicchioli, et al in this journal (June 18, 2019).

Ledford, Heidi. CRISPR, the Disruptor. Nature. 522/21, 2015. We note this survey article within a topical section to report this breakthrough fast, low cost, easy and effective method of genetic editing and regulation to add, delete, or change specific gene sequences. CRISPR means “clustered regularly interspaced short palindromic repeats.” Among many reports, see also Editing Humanity in the August 22, 2015 issue of The Economist. One wonders what kind of self-sequencing uniVerse this might be, whence a human phenomenon can learn to read, curate and intentionally begin a new genesis creation.

Lepora, Nathan, et al. The State of the Art in Biomimetics. Bioinspiration & Biomimetics. 8/013001, 2013. Since evolutionary Nature has a billion years experience, we would be well advised and inspired to “mimic,” and intentionally continue on such biological design principles for better, more truly viable, organic societies. In this 21st century dedicated journal, University of Sheffield, UK, and Universitat Pompeu Fabra, Synthetic Perceptive, Emotive and Cognitive Systems, Spain imagineers provide a succinct survey of past art and future promise for this imperative project.

Biomimetics is a research field that is achieving particular prominence through an explosion of new discoveries in biology and engineering. The field concerns novel technologies developed through the transfer of function from biological systems. To analyze the impact of this field within engineering and related sciences, we compiled an extensive database of publications for study with network-based information analysis techniques. Criteria included publications by year and journal or conference, and subject areas judged by popular and common terms in titles. Our results reveal that this research area has expanded rapidly from less than 100 papers per year in the 1990s to several thousand papers per year in the first decade of this century. Moreover, this research is having impact across a variety of research themes, spanning robotics, computer science and bioengineering. In consequence, biomimetics is becoming a leading paradigm for the development of new technologies that will potentially lead to significant scientific, societal and economic impact in the near future. (Abstract)

Li, yang, et al. Cooperativity Principles in Self-Assembled Nanomedicine. Chemical Reviews. Online April, 2018. UT Southwestern Medical Center and Peking University pharmaceutical biophysicists write a 24 page illustrated tutorial to these frontiers of “supramolecular self-assembly” as human intellect begins to take over for palliative and procreative benefit. By this view, biochemical such as enzymes similarly appear to cooperate with each other as they induce vital phase transitions. Nucleic acids are particularly amenable at they form many structures via cooperative aggregations beyond the double helix.

Nanomedicine is a discipline that applies nanoscience and nanotechnology principles to the prevention, diagnosis, and treatment of human diseases. Self-assembly of molecular components is becoming a common strategy in the design and syntheses of nanomaterials for biomedical applications. In both natural and synthetic self-assembled nanostructures, molecular cooperativity is emerging as an important hallmark. In many cases, interplay of many types of noncovalent interactions leads to dynamic nanosystems with emergent properties where the whole is bigger than the sum of the parts. In this review, we provide a comprehensive analysis of the cooperativity principles in multiple self-assembled nanostructures. In selected systems, we describe the examples on how to leverage molecular cooperativity to design nanomedicine with improved diagnostic precision and therapeutic efficacy in medicine. (Abstract)

Loman, Nicholas and Mark Pallen. Twenty Years of Bacterial Genome Sequencing. Nature Reviews Microbiology. 13/12, 2015. University of Birmingham and Warwick Medical School microbiologists proffer a cogent retrospect of progress from mid 1990s techniques through their iterative and revolutionary sophistication to today’s hyper-automation and computation. The British company Oxford Nanopore (search herein), which the lead author is affiliated with, is given as an instance of the latest methods. From their website under Publications, a YouTube talk by Loman with A Sequencing Singularity title can be accessed.

Twenty years ago, the publication of the first bacterial genome sequence, from Haemophilus influenzae, shook the world of bacteriology. In this Timeline, we review the first two decades of bacterial genome sequencing, which have been marked by three revolutions: whole-genome shotgun sequencing, high-throughput sequencing and single-molecule long-read sequencing. We summarize the social history of sequencing and its impact on our understanding of the biology, diversity and evolution of bacteria, while also highlighting spin-offs and translational impact in the clinic. We look forward to a 'sequencing singularity', where sequencing becomes the method of choice for as-yet unthinkable applications in bacteriology and beyond. (Abstract)

Loman, Nick. The Sequencing Singularity?. nanoporetech.com/resource-centre/videos/sequencing-singularity. A half hour 2016 YouTube presentation by the University of Birmingham genetic bioinformatics researcher, which is also available on the Oxford Nanopore site. The phrase was first cited in a 2015 Nature Reviews Microbiology article above to express how novel human abilities are beginning to curate, edit, and author anew life’s informative code.

Sequencing is poised to disrupt clinical practice. Whole swathes of diagnostic tests may eventually be replaced with a single assay - sequencing - as we reach the "sequencing singularity". I will review recent advances in the use of nanopore sequencing for clinical microbiology and human genetics, including our collaborations on viral and bacterial diagnostic sequencing, real-time surveillance, direct RNA and human whole-genome sequencing, and discuss the opportunities and barriers around moving to sequencing as a routine test in the clinic.

Nick works as Professor of Microbial Genomics and Bioinformatics in the Institute for Microbiology and Infection at the University of Birmingham. His research explores the use of cutting-edge genomics and metagenomics approaches to the diagnosis, treatment and surveillance of infectious disease. Nick has so far used high-throughput sequencing to investigate outbreaks of important Gram-negative multi-drug resistant pathogens, and recently helped establish real-time genomic surveillance of Ebola in Guinea. His current work focuses on the development of novel sequencing and bioinformatics methods to aid the interpretation of genome and metagenome scale data generated in clinical and public health microbiology. (NL website)

Maharbiz, Michel. Synthetic Multicellularity. Trends in Cell Biology. 22/12, 2012. A University of California, Berkeley, computer engineer considers early explorations of how complex systems biology might be availed to commence the respectful creation of utile multicellular organisms. The motivation and standard of behavior for such endeavors would be their service toward a better, sustainable world for life and people. See also in this dedicated issue “Directed Cytoskeleton Self-Organization” by Timothee Vignaud, et al, which alludes to independent principles of organic form and vitality.

Concluding Remarks That this has profound ethical and societal consequences cannot be overstated. There is – perhaps controversially – an ultimately ecological rationale for this vision. For the most part, the technological base created by the industrial revolution communicates poorly with the underlying organic technology of the planet. The rapid expansion of man-made, acellular, resource-consuming, and waste-producing constructs is in large part responsible for the ecological and climactic mess we are in. Mindful of the vast ethical and societal questions raised, it is worth considering a future wherein our homes, our factories, and our consumer gadgets can ‘understand’ the language of organic systems around them and form part of a related or hybrid framework of information and material exchange. This notion – that our societal artifacts should be mindful of their natural surroundings – has long and deep roots in many cultures and has modern reflections in, for example, the natural building movements. It is my contention that the development of synthetic multicellular – and likely hybrid- systems is a step down this transformative road. (621-622)

The cytoskeleton architecture supports many cellular functions. Cytoskeleton networks form complex intracellular structures that vary during the cell cycle and between different cell types according to their physiological role. These structures result…, from the interplay between intrinsic self-organization properties and the conditions imposed by spatial boundaries. Along these boundaries, cytoskeleton filaments are anchored, repulsed, aligned, or reoriented. Such local effects can propagate alterations throughout the network and guide cytoskeleton assembly over relatively large distances. The experimental manipulation of spatial boundaries using microfabrication methods has revealed the underlying physical processes directing cytoskeleton self-organization. Here we review, step-by-step, from molecules to tissues, how the rules that govern assembly have been identified. We describe how complementary approaches, all based on controlling geometric conditions, from in vitro reconstruction to in vivo observation, shed new light on these fundamental organizing principles. (Vignaud Abstract)

Majumder, Sagardip and Allen Liu. Bottom-Up Synthetic Biology: Modular Design for Making Artificial Platelets. Physical Biology. 15/1, 2018. An article by University of Michigan bioengineers for a dedicated issue with the first title, edited. We quote the issue summary, which also applies to this paper. One could then reflect that in a cosmic genesis its natural evolutionary methods seem meant to pass to and be enhanced by our humankinder evolitionary phase.

Spatially organized cellular processes arise from the interactions of nanometer building blocks. These emergent behaviors cannot be understood by knowing the parts alone, but rather how they interact. A central challenge in cell biology is thus to understand how cellular processes are organized spatiotemporally from the component parts. One powerful approach in such quest is bottom-up cellular reconstitution as an attempt to recreate the complexity of cellular life. Many examples of bottom-up reconstitution have come from various cytoskeletal, molecular motors, and membrane trafficking systems and provide vivid demonstrations of large-scale biomimetic behaviors. In addition, the use of cell-free extracts provides an experimental platform for connecting genetic information to modifying component parts. This special issue highlights both current cellular reconstitution efforts from purified proteins as well as cell-free systems of DNA-programmed behaviors in artificial cells.

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