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  1. Article ; Online: There’s Plenty of Room Right Here

    Joshua Bongard / Michael Levin

    Biomimetics, Vol 8, Iss 110, p

    Biological Systems as Evolved, Overloaded, Multi-Scale Machines

    2023  Volume 110

    Abstract: The applicability of computational models to the biological world is an active topic of debate. We argue that a useful path forward results from abandoning hard boundaries between categories and adopting an observer-dependent, pragmatic view. Such a view ...

    Abstract The applicability of computational models to the biological world is an active topic of debate. We argue that a useful path forward results from abandoning hard boundaries between categories and adopting an observer-dependent, pragmatic view. Such a view dissolves the contingent dichotomies driven by human cognitive biases (e.g., a tendency to oversimplify) and prior technological limitations in favor of a more continuous view, necessitated by the study of evolution, developmental biology, and intelligent machines. Form and function are tightly entwined in nature, and in some cases, in robotics as well. Thus, efforts to re-shape living systems for biomedical or bioengineering purposes require prediction and control of their function at multiple scales. This is challenging for many reasons, one of which is that living systems perform multiple functions in the same place at the same time. We refer to this as “polycomputing”—the ability of the same substrate to simultaneously compute different things, and make those computational results available to different observers. This ability is an important way in which living things are a kind of computer, but not the familiar, linear, deterministic kind; rather, living things are computers in the broad sense of their computational materials, as reported in the rapidly growing physical computing literature. We argue that an observer-centered framework for the computations performed by evolved and designed systems will improve the understanding of mesoscale events, as it has already done at quantum and relativistic scales. To develop our understanding of how life performs polycomputing, and how it can be convinced to alter one or more of those functions, we can first create technologies that polycompute and learn how to alter their functions. Here, we review examples of biological and technological polycomputing, and develop the idea that the overloading of different functions on the same hardware is an important design principle that helps to understand and build both ...
    Keywords biology ; computer science ; robot ; artificial life ; artificial intelligence ; machine learning ; Technology ; T
    Subject code 120
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The dolichosigma partially located on the right

    Michael Levin

    World Journal of Nuclear Medicine, Vol 18, Iss 04, Pp 440-

    How justified is the concept of the right slow transit constipation?

    2019  Volume 442

    Keywords Medical physics. Medical radiology. Nuclear medicine ; R895-920
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher Wolters Kluwer Medknow Publications
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Balancing risk and benefit of SARS-CoV-2 vaccines in children

    Michael Levin / Elizabeth Whittaker

    The Lancet Regional Health. Europe, Vol 18, Iss , Pp 100412- (2022)

    2022  

    Keywords Public aspects of medicine ; RA1-1270
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Competency in Navigating Arbitrary Spaces as an Invariant for Analyzing Cognition in Diverse Embodiments

    Chris Fields / Michael Levin

    Entropy, Vol 24, Iss 819, p

    2022  Volume 819

    Abstract: One of the most salient features of life is its capacity to handle novelty and namely to thrive and adapt to new circumstances and changes in both the environment and internal components. An understanding of this capacity is central to several fields: ... ...

    Abstract One of the most salient features of life is its capacity to handle novelty and namely to thrive and adapt to new circumstances and changes in both the environment and internal components. An understanding of this capacity is central to several fields: the evolution of form and function, the design of effective strategies for biomedicine, and the creation of novel life forms via chimeric and bioengineering technologies. Here, we review instructive examples of living organisms solving diverse problems and propose competent navigation in arbitrary spaces as an invariant for thinking about the scaling of cognition during evolution. We argue that our innate capacity to recognize agency and intelligence in unfamiliar guises lags far behind our ability to detect it in familiar behavioral contexts. The multi-scale competency of life is essential to adaptive function, potentiating evolution and providing strategies for top-down control (not micromanagement) to address complex disease and injury. We propose an observer-focused viewpoint that is agnostic about scale and implementation, illustrating how evolution pivoted similar strategies to explore and exploit metabolic, transcriptional, morphological, and finally 3D motion spaces. By generalizing the concept of behavior, we gain novel perspectives on evolution, strategies for system-level biomedical interventions, and the construction of bioengineered intelligences. This framework is a first step toward relating to intelligence in highly unfamiliar embodiments, which will be essential for progress in artificial intelligence and regenerative medicine and for thriving in a world increasingly populated by synthetic, bio-robotic, and hybrid beings.
    Keywords physiology ; anatomical morphospace ; basal cognition ; Science ; Q ; Astrophysics ; QB460-466 ; Physics ; QC1-999
    Subject code 120
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Minimal Developmental Computation

    Santosh Manicka / Michael Levin

    Entropy, Vol 24, Iss 107, p

    A Causal Network Approach to Understand Morphogenetic Pattern Formation

    2022  Volume 107

    Abstract: What information-processing strategies and general principles are sufficient to enable self-organized morphogenesis in embryogenesis and regeneration? We designed and analyzed a minimal model of self-scaling axial patterning consisting of a cellular ... ...

    Abstract What information-processing strategies and general principles are sufficient to enable self-organized morphogenesis in embryogenesis and regeneration? We designed and analyzed a minimal model of self-scaling axial patterning consisting of a cellular network that develops activity patterns within implicitly set bounds. The properties of the cells are determined by internal ‘genetic’ networks with an architecture shared across all cells. We used machine-learning to identify models that enable this virtual mini-embryo to pattern a typical axial gradient while simultaneously sensing the set boundaries within which to develop it from homogeneous conditions—a setting that captures the essence of early embryogenesis. Interestingly, the model revealed several features (such as planar polarity and regenerative re-scaling capacity) for which it was not directly selected, showing how these common biological design principles can emerge as a consequence of simple patterning modes. A novel “causal network” analysis of the best model furthermore revealed that the originally symmetric model dynamically integrates into intercellular causal networks characterized by broken-symmetry, long-range influence and modularity, offering an interpretable macroscale-circuit-based explanation for phenotypic patterning. This work shows how computation could occur in biological development and how machine learning approaches can generate hypotheses and deepen our understanding of how featureless tissues might develop sophisticated patterns—an essential step towards predictive control of morphogenesis in regenerative medicine or synthetic bioengineering contexts. The tools developed here also have the potential to benefit machine learning via new forms of backpropagation and by leveraging the novel distributed self-representation mechanisms to improve robustness and generalization.
    Keywords biological computation ; developmental patterning ; distributed information processing ; collective phenomena ; causal information flow ; biological circuits ; Science ; Q ; Astrophysics ; QB460-466 ; Physics ; QC1-999
    Subject code 006
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: The nonlinearity of regulation in biological networks

    Santosh Manicka / Kathleen Johnson / Michael Levin / David Murrugarra

    npj Systems Biology and Applications, Vol 9, Iss 1, Pp 1-

    2023  Volume 9

    Abstract: Abstract The extent to which the components of a biological system are (non)linearly regulated determines how amenable they are to therapy and control. To better understand this property termed “regulatory nonlinearity”, we analyzed a suite of 137 ... ...

    Abstract Abstract The extent to which the components of a biological system are (non)linearly regulated determines how amenable they are to therapy and control. To better understand this property termed “regulatory nonlinearity”, we analyzed a suite of 137 published Boolean network models, containing a variety of complex nonlinear regulatory interactions, using a probabilistic generalization of Boolean logic that George Boole himself had proposed. Leveraging the continuous-nature of this formulation, we used Taylor decomposition to approximate the models with various levels of regulatory nonlinearity. A comparison of the resulting series of approximations of the biological models with appropriate random ensembles revealed that biological regulation tends to be less nonlinear than expected, meaning that higher-order interactions among the regulatory inputs tend to be less pronounced. A further categorical analysis of the biological models revealed that the regulatory nonlinearity of cancer and disease networks could not only be sometimes higher than expected but also be relatively more variable. We show that this variation is caused by differences in the apportioning of information among the various orders of regulatory nonlinearity. Our results suggest that there may have been a weak but discernible selection pressure for biological systems to evolve linear regulation on average, but for certain systems such as cancer, on the other hand, to simultaneously evolve more nonlinear rules.
    Keywords Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Information integration during bioelectric regulation of morphogenesis of the embryonic frog brain

    Santosh Manicka / Vaibhav P. Pai / Michael Levin

    iScience, Vol 26, Iss 12, Pp 108398- (2023)

    2023  

    Abstract: Summary: Spatiotemporal patterns of cellular resting potential regulate several aspects of development. One key aspect of the bioelectric code is that transcriptional and morphogenetic states are determined not by local, single-cell, voltage levels but ... ...

    Abstract Summary: Spatiotemporal patterns of cellular resting potential regulate several aspects of development. One key aspect of the bioelectric code is that transcriptional and morphogenetic states are determined not by local, single-cell, voltage levels but by specific distributions of voltage across cell sheets. We constructed and analyzed a minimal dynamical model of collective gene expression in cells based on inputs of multicellular voltage patterns. Causal integration analysis revealed a higher-order mechanism by which information about the voltage pattern was spatiotemporally integrated into gene activity, as well as a division of labor among and between the bioelectric and genetic components. We tested and confirmed predictions of this model in a system in which bioelectric control of morphogenesis regulates gene expression and organogenesis: the embryonic brain of the frog Xenopus laevis. This study demonstrates that machine learning and computational integration approaches can advance our understanding of the information-processing underlying morphogenetic decision-making, with a potential for other applications in developmental biology and regenerative medicine.
    Keywords Biomimetics ; Embryology ; Complex system biology ; In silico biology ; Model organism ; Science ; Q
    Subject code 612
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Synthetic living machines

    Mo R. Ebrahimkhani / Michael Levin

    iScience, Vol 24, Iss 5, Pp 102505- (2021)

    A new window on life

    2021  

    Abstract: Summary: Increased control of biological growth and form is an essential gateway to transformative medical advances. Repairing of birth defects, restoring lost or damaged organs, normalizing tumors, all depend on understanding how cells cooperate to make ...

    Abstract Summary: Increased control of biological growth and form is an essential gateway to transformative medical advances. Repairing of birth defects, restoring lost or damaged organs, normalizing tumors, all depend on understanding how cells cooperate to make specific, functional large-scale structures. Despite advances in molecular genetics, significant gaps remain in our understanding of the meso-scale rules of morphogenesis. An engineering approach to this problem is the creation of novel synthetic living forms, greatly extending available model systems beyond evolved plant and animal lineages. Here, we review recent advances in the emerging field of synthetic morphogenesis, the bioengineering of novel multicellular living bodies. Emphasizing emergent self-organization, tissue-level guided self-assembly, and active functionality, this work is the essential next generation of synthetic biology. Aside from useful living machines for specific functions, the rational design and analysis of new, coherent anatomies will greatly increase our understanding of foundational questions in evolutionary developmental and cell biology.
    Keywords developmental biology ; bioengineering ; synthetic biology ; Science ; Q
    Subject code 501 ; 120
    Language English
    Publishing date 2021-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Behaviorist approaches to investigating memory and learning

    Charles I. Abramson / Michael Levin

    Communicative & Integrative Biology, Vol 14, Iss 1, Pp 230-

    A primer for synthetic biology and bioengineering

    2021  Volume 247

    Abstract: The fields of developmental biology, biomedicine, and artificial life are being revolutionized by advances in synthetic morphology. The next phase of synthetic biology and bioengineering is resulting in the construction of novel organisms (biobots), ... ...

    Abstract The fields of developmental biology, biomedicine, and artificial life are being revolutionized by advances in synthetic morphology. The next phase of synthetic biology and bioengineering is resulting in the construction of novel organisms (biobots), which exhibit not only morphogenesis and physiology but functional behavior. It is now essential to begin to characterize the behavioral capacity of novel living constructs in terms of their ability to make decisions, form memories, learn from experience, and anticipate future stimuli. These synthetic organisms are highly diverse, and often do not resemble familiar model systems used in behavioral science. Thus, they represent an important context in which to begin to unify and standardize vocabulary and techniques across developmental biology, behavioral ecology, and neuroscience. To facilitate the study of behavior in novel living systems, we present a primer on techniques from the behaviorist tradition that can be used to probe the functions of any organism – natural, chimeric, or synthetic – regardless of the details of their construction or origin. These techniques provide a rich toolkit for advancing the fields of synthetic bioengineering, evolutionary developmental biology, basal cognition, exobiology, and robotics.
    Keywords behaviorism ; synthetic morphology ; biobot ; memory ; learning ; basal cognition ; Biology (General) ; QH301-705.5
    Subject code 120
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Taylor & Francis Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Living Things Are Not (20th Century) Machines

    Joshua Bongard / Michael Levin

    Frontiers in Ecology and Evolution, Vol

    Updating Mechanism Metaphors in Light of the Modern Science of Machine Behavior

    2021  Volume 9

    Abstract: One of the most useful metaphors for driving scientific and engineering progress has been that of the “machine.” Much controversy exists about the applicability of this concept in the life sciences. Advances in molecular biology have revealed numerous ... ...

    Abstract One of the most useful metaphors for driving scientific and engineering progress has been that of the “machine.” Much controversy exists about the applicability of this concept in the life sciences. Advances in molecular biology have revealed numerous design principles that can be harnessed to understand cells from an engineering perspective, and build novel devices to rationally exploit the laws of chemistry, physics, and computation. At the same time, organicists point to the many unique features of life, especially at larger scales of organization, which have resisted decomposition analysis and artificial implementation. Here, we argue that much of this debate has focused on inessential aspects of machines – classical properties which have been surpassed by advances in modern Machine Behavior and no longer apply. This emerging multidisciplinary field, at the interface of artificial life, machine learning, and synthetic bioengineering, is highlighting the inadequacy of existing definitions. Key terms such as machine, robot, program, software, evolved, designed, etc., need to be revised in light of technological and theoretical advances that have moved past the dated philosophical conceptions that have limited our understanding of both evolved and designed systems. Moving beyond contingent aspects of historical and current machines will enable conceptual tools that embrace inevitable advances in synthetic and hybrid bioengineering and computer science, toward a framework that identifies essential distinctions between fundamental concepts of devices and living agents. Progress in both theory and practical applications requires the establishment of a novel conception of “machines as they could be,” based on the profound lessons of biology at all scales. We sketch a perspective that acknowledges the remarkable, unique aspects of life to help re-define key terms, and identify deep, essential features of concepts for a future in which sharp boundaries between evolved and designed systems will not exist.
    Keywords biology ; computer science ; robot ; artificial life ; machine learning ; Evolution ; QH359-425 ; Ecology ; QH540-549.5
    Subject code 501
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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