Michael Levin

Michael Levin
Tufts University | Tufts · Allen Discovery Center, and Department of Biology

PhD

About

569
Publications
94,996
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18,667
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Introduction
Michael Levin heads the Allen Discovery Center at Tufts University. His lab works at the intersection of developmental biophysics, computer science, and primitive cognition. See more at www.drmichaellevin.org and allencenter.tufts.edu

Publications

Publications (569)
Article
Full-text available
Background During embryogenesis lateral symmetry is broken, giving rise to Left/Right (L/R) breast tissues with distinct identity. L/R-sided breast tumors exhibit consistently-biased incidence, gene expression, and DNA methylation. We postulate that a differential L/R tumor-microenvironment crosstalk generates different tumorigenesis mechanisms. M...
Preprint
We show how any system with morphological degrees of freedom and locally limited free energy will, under the constraints of the free energy principle, evolve toward a neuromorphic morphology that supports hierarchical computations in which each level of the hierarchy enacts a coarse-graining of its inputs, and dually a fine-graining of its outputs....
Preprint
Nonlinearity is a characteristic of complex biological regulatory networks that has implications ranging from therapy to control. To better understand its nature, we analyzed a suite of published Boolean network models, containing a variety of complex nonlinear interactions, using a probabilistic generalization of Boolean logic that George Boole hi...
Article
Full-text available
Current therapeutic strategies against bacterial infections focus on reduction of pathogen load using antibiotics; however, stimulation of host tolerance to infection in the presence of pathogens might offer an alternative approach. Computational transcriptomics and Xenopus laevis embryos are used to discover infection response pathways, identify p...
Article
Conceptual and mathematical models of neurons have lagged behind empirical understanding for decades. Here we extend previous work in modeling biological systems with fully scale-independent quantum information-theoretic tools to develop a uniform, scalable representation of synapses, dendritic and axonal processes, neurons, and local networks of n...
Article
The Free Energy Principle (FEP) states that under suitable conditions of weak coupling, random dynamical systems with sufficient degrees of freedom will behave so as to minimize an upper bound, formalized as a variational free energy, on surprisal (a.k.a., self-information). This upper bound can be read as a Bayesian prediction error. Equivalently,...
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Evolution is full of coevolving systems characterized by complex spatio-temporal interactions that lead to intertwined processes of adaptation. Yet, how adaptation across multiple levels of temporal scales and biological complexity is achieved remains unclear. Here, we formalize how evolutionary multi-scale processing underlying adaptation constitu...
Preprint
One of the most salient features of life is its capacity to handle novelty: to thrive and adapt to new circumstances and changes of both 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 nove...
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Synthetic biology and bioengineering provide the opportunity to create novel embodied cognitive systems (otherwise known as minds) in a very wide variety of chimeric architectures combining evolved and designed material and software. These advances are disrupting familiar concepts in the philosophy of mind, and require new ways of thinking about an...
Article
Biological organisms learn from interactions with their environment throughout their lifetime. For artificial systems to successfully act and adapt in the real world, it is desirable to similarly be able to learn on a continual basis. This challenge is known as lifelong learning, and remains to a large extent unsolved. In this Perspective article,...
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It is difficult to develop effective treatments for neurodevelopmental genetic disorders, such as Rett syndrome, which are caused by a single gene mutation but trigger changes in numerous other genes, and thereby also severely impair functions of organs beyond the central nervous system (CNS). This challenge is further complicated by the lack of su...
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Glioblastoma is a lethal brain cancer that commonly recurs after tumor resection and chemotherapy treatment. Depolarized resting membrane potentials and an acidic intertumoral extracellular pH have been associated with a proliferative state and drug resistance, suggesting that forced hyperpolarization and disruption of proton pumps in the plasma me...
Preprint
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A common view in the neuroscience community is that memory is encoded in the connection strength between neurons. This perception led artificial neural network models to focus on connection weights as the key variables to modulate learning. In this paper, we present a prototype for weightless spiking neural networks that can perform a simple classi...
Article
Limb regeneration is a frontier in biomedical science. Identifying triggers of innate morphogenetic responses in vivo to induce the growth of healthy patterned tissue would address the needs of millions of patients, from diabetics to victims of trauma. Organisms such as Xenopus laevis-whose limited regenerative capacities in adulthood mirror those...
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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 ar...
Preprint
Full-text available
Conceptual and mathematical models of neurons have lagged behind empirical understanding for decades. Here we extend previous work in modeling biological systems with fully scale-independent quantum information-theoretic tools to develop a uniform, scalable representation of synapses, dendritic and axonal processes, neurons, and local networks of n...
Article
Full-text available
Background There is a critical need to better understand the mechanisms that drive local cell invasion and metastasis to develop new therapeutics targeting metastatic disease. Bioelectricity is an important mediator of cellular processes and changes in the resting membrane potential (RMP) are associated with increased cancer cell invasion. However,...
Preprint
Full-text available
The Free Energy Principle (FEP) states that under suitable conditions of weak coupling, random dynamical systems with sufficient degrees of freedom will behave so as to minimize an upper bound, formalized as a variational free energy, on surprisal (a.k.a., self-information). This upper bound can be read as a Bayesian prediction error. Equivalently,...
Preprint
Full-text available
Synthetic biology and bioengineering provide the opportunity to create novel embodied cognitive systems (otherwise known as minds) in a very wide variety of chimeric architectures combining evolved and designed material and software. These advances are disrupting familiar concepts in the philosophy of mind, and require new ways of thinking about an...
Preprint
Full-text available
A bstract Nonlinearity is a characteristic of complex biological regulatory networks that has implications ranging from therapy to control. To better understand its nature, we analyzed a suite of published Boolean network models, containing a variety of complex nonlinear interactions, with an approach involving a probabilistic generalization of Boo...
Article
Full-text available
The internal workings of biological systems are notoriously difficult to understand. Due to the prevalence of noise and degeneracy in evolved systems, in many cases the workings of everything from gene regulatory networks to protein-protein interactome networks remain black boxes. One consequence of this black-box nature is that it is unclear at wh...
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Full-text available
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...
Article
Full-text available
All living systems perpetuate themselves via growth in or on the body, followed by splitting, budding, or birth. We find that synthetic multicellular assemblies can also replicate kinematically by moving and compressing dissociated cells in their environment into functional self-copies. This form of perpetuation, previously unseen in any organism,...
Article
Despite the immense progress in genetics and cell biology, major knowledge gaps remain with respect to prediction and control of the global morphologies that will result from the cooperation of cells with known genomes. The understanding of cooperativity, competition, and synergy across diverse biological scales has been obscured by a focus on stan...
Preprint
Full-text available
Background: During embryogenesis, lateral symmetry is broken giving rise to Left/Right (L/R) breast tissues with distinct identity. L/R-sided breast tumors exhibit consistently-biased incidence, gene expression, and DNA methylation. We postulate that a differential L/R tumor-microenvironment crosstalk generates different tumorigenesis mechanisms. M...
Article
Full-text available
Electric potential distributions can act as instructive pre-patterns for development, regeneration, and tumorigenesis in cell systems. The biophysical states influence transcription, proliferation, cell shape, migration, and differentiation through biochemical and biomechanical downstream transduction processes. A major knowledge gap is the origin...
Preprint
Prior studies of decision-making generally assume a fixed agent which maximizes utility among its various options. Physarum polycephalum is a popular model for basal cognition that can be cut into pieces that may or may not re-join. We exploited this capacity to develop a novel assay in which radical changes to the agent itself are among the option...
Preprint
Current therapeutic strategies against bacterial infections focus on reduction of pathogen load through antibiotics; however, stimulation of host tolerance to infection might offer an alternative approach. Here we used computational transcriptomics and a Xenopus embryo infection model to rapidly discover infection response pathways, identify potent...
Article
Full-text available
Cellular communication is important in all aspects of tissue and organism functioning, from the level of single cells, two discreet populations, and distant tissues of the body. Long distance communication networks integrate individual cells into tissues to maintain a complex organism during development, but when communication between cells goes aw...
Article
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Many biological organisms regenerate structure and function after damage. Despite the long history of research on molecular mechanisms, many questions remain about algorithms by which cells can cooperate towards the same invariant morphogenetic outcomes. Therefore, conceptual frameworks are needed not only for motivating hypotheses for advancing th...
Article
Morphogenesis during development and regeneration requires cells to communicate and cooperate toward the construction of complex anatomical structures. One important set of mechanisms for coordinating growth and form occurs via developmental bioelectricity—the dynamics of cellular networks driving changes of resting membrane potential which interfa...
Article
Full-text available
The unicellular protist Physarum polycephalum is an important emerging model for understanding how aneural organisms process information toward adaptive behavior. Here, it is revealed that Physarum can use mechanosensation to reliably make decisions about distant objects in its environment, preferentially growing in the direction of heavier, substr...
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Biomechanical Signaling Physarum polycephalum, a slime mold with one cell and no brain, is a remarkable new model for understanding basal cognition. Its living material deforms its own structure to interact with the objects around it. In article number 2008161, Michael Levin and co-workers show that Physarum senses strain in its substrate, using bi...
Article
Limb loss due to traumatic injury or amputation is a major biomedical burden. Many vertebrates exhibit the ability to form and pattern normal limbs during embryogenesis from amorphous clusters of precursor cells, hinting that this process could perhaps be activated later in life to rebuild missing or damaged limbs. Indeed, some animals, such as sal...
Article
Theories of consciousness and cognition that assume a neural substrate automatically regard phylogenetically basal, nonneural systems as nonconscious and noncognitive. Here, we advance a scale-free characterization of consciousness and cognition that regards basal systems, including synthetic constructs, as not only informative about the structure...
Article
Complex anatomical form is regulated in part by endogenous physiological communication between cells; however, the dynamics by which gap junctional (GJ) states across tissues regulate morphology are still poorly understood. We employed a biophysical modeling approach combining different signaling molecules (morphogens) to qualitatively describe the...
Article
Biological information processing is generally assumed to be classical. Measured cellular energy budgets of both prokaryotes and eukaryotes, however, fall orders of magnitude short of the power required to maintain classical states of protein conformation and localization at the Å, fs scales predicted by single-molecule decoherence calculations and...
Article
Full-text available
Cephalopods camouflage abilities arise from highly specialized chromatic elements in their skin, chromatophores, iridophores, and leucophores, that enable them to display complex and rapidly changing color patterns. Despite the extensive study of these chromatic elements in squid and cuttlefish, full characterization of their individual optical res...
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One of the key differentiators between biological and artificial systems is the dynamic plasticity of living tissues, enabling adaptation to different environmental conditions, tasks, or damage by reconfiguring physical structure and behavioral control policies. Lack of dynamic plasticity is a significant limitation for artificial systems that must...
Article
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Recent advances in soft robotics have allowed robots to begin changing their shape in response to evolving mission requirements. Next‐generation robots will be able to sense changes in their environment, automatically determine an optimal shape for the new landscape, and then morph into that shape to improve their efficiency. In article number 2002...
Article
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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 r...
Article
One lens with which to understand the complex phenomenon of cancer is that of developmental biology. Cancer is the inevitable consequence of a breakdown of the communication that enables individual cells to join into computational networks that work towards large-scale, morphogenetic goals instead of more primitive, unicellular objectives. This per...
Preprint
Full-text available
There is a critical need to better understand the mechanisms that drive local cell invasion and metastasis to develop new therapeutics targeting metastatic disease. Bioelectricity is an important mediator of cellular processes and changes in the resting membrane potential (RMP) are associated with increased cancer cell invasion. However, the mechan...
Article
Full-text available
Birch, Ginsburg, and Jablonka lay out a very convincing case for an important transition marker: unlimited associative learning (UAL). Especially welcome are the empirical predictions. I focus here not on the question of how to infer phenomenal consciousness from this behavioral metric, but on possible novel applications of this useful and fundamen...
Article
How are individual cell behaviors coordinated toward invariant large-scale anatomical outcomes in development and regeneration despite unpredictable perturbations? Endogenous distributions of membrane potentials, produced by ion channels and gap junctions, are present across all tissues. These bioelectrical networks process morphogenetic informatio...
Article
Robot swarms have, to date, been constructed from artificial materials. Motile biological constructs have been created from muscle cells grown on precisely shaped scaffolds. However, the exploitation of emergent self-organization and functional plasticity into a self-directed living machine has remained a major challenge. We report here a method fo...
Preprint
Biological information processing is generally assumed to be classical. Measured cellular energy budgets of both prokaryotes and eukaryotes, however, fall orders of magnitude short of the power required to maintain classical states of protein conformation and localization at the \AA, fs scales predicted by single-molecule decoherence calculations a...
Article
Nervous systems’ computational abilities are an evolutionary innovation, specializing and speed-optimizing ancient biophysical dynamics. Bioelectric signalling originated in cells' communication with the outside world and with each other, enabling cooperation towards adaptive construction and repair of multicellular bodies. Here, we review the emer...
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This article is part of the theme issue ‘Basal cognition: multicellularity, neurons and the cognitive lens'.
Article
The premise of this two-part theme issue is simple: the cognitive sciences should join the rest of the life sciences in how they approach the quarry within their research domain. Specifically, understanding how organisms on the lower branches of the phylogenetic tree become familiar with, value and exploit elements of an ecological niche while avoi...
Preprint
Full-text available
Robots deployed at orders of magnitude different size scales, and that retain the same desired behavior at any of those scales, would greatly expand the environments in which the robots could operate. However it is currently not known whether such robots exist, and, if they do, how to design them. Since self similar structures in nature often exhib...
Article
Though neuroscientists have historically relied upon measurement of established nervous systems, contemporary advances in bioengineering have made it possible to design and build artificial neural tissues with which to investigate normative and diseased states [[1], [2], [3], [4], [5]] (Nisbet et al., 2008; Phillips et al., 2005; Stabenfeldt et al....
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Full-text available
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 b...
Article
Full-text available
Gene regulatory networks GRNs process important information in developmental biology and biomedicine. A key knowledge gap concerns how their responses change over time. Hypothesizing long-term changes of dynamics induced by transient prior events, we created a computational framework for defining and identifying diverse types of memory in candidate...
Preprint
Full-text available
Regeneration requires the production of large numbers of new cells, and thus cell division regulators, particularly ERK signaling, are critical in regulating this process. In the highly regenerative planarian flatworm, questions remain as to whether ERK signaling controls overall regeneration or plays a head-specific role. Here we show that ERK inh...
Chapter
Embryogenesis, as well as regeneration, is increasingly recognized to be orchestrated by an interplay of transcriptional and bioelectric networks. Spatiotemporal patterns of resting potentials direct the size, shape, and locations of numerous organ primordia during patterning. These bioelectrical properties are established by the function of ion ch...
Article
Full-text available
Infections have numerous effects on the brain. However, possible roles of the brain in protecting against infection, and the developmental origin and role of brain signaling in immune response, are largely unknown. We exploited a unique Xenopus embryonic model to reveal control of innate immune response to pathogenic E. coli by the developing brain...
Article
Full-text available
Bioelectronics In article number 2000140, Michael Levin, Marcella Gomez, Marco Rolandi, and co‐workers present bioelectronics coupled with machine learning for intelligent control of cellular function. The authors set and maintain the membrane voltage of human pluripotent stem cells with H⁺‐conducting bioelectronic devices. The H⁺‐devices are actua...
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Meaning has traditionally been regarded as a problem for philosophers and psychologists. Advances in cognitive science since the early 1960s, however, broadened discussions of meaning, or more technically, the semantics of perceptions, representations, and/or actions, into biology and computer science. Here, we review the notion of “meaning” as it...