SBMLtoODEjax: Efficient Simulation and Optimization of Biological Network Models in JAXMayalen Etcheverry, Michael Levin, Clément Moulin-Frier et al.
Advances in bioengineering and biomedicine demand a deep understanding of the dynamic behavior of biological systems, ranging from protein pathways to complex cellular processes. Biological networks like gene regulatory networks and protein pathways are key drivers of embryogenesis and physiological processes. Comprehending their diverse behaviors is essential for tackling diseases, including cancer, as well as for engineering novel biological constructs. Despite the availability of extensive mathematical models represented in Systems Biology Markup Language (SBML), researchers face significant challenges in exploring the full spectrum of behaviors and optimizing interventions to efficiently shape those behaviors. Existing tools designed for simulation of biological network models are not tailored to facilitate interventions on network dynamics nor to facilitate automated discovery. Leveraging recent developments in machine learning (ML), this paper introduces SBMLtoODEjax, a lightweight library designed to seamlessly integrate SBML models with ML-supported pipelines, powered by JAX. SBMLtoODEjax facilitates the reuse and customization of SBML-based models, harnessing JAX's capabilities for efficient parallel simulations and optimization, with the aim to accelerate research in biological network analysis.
Scalable sim-to-real transfer of soft robot designsSam Kriegman, Amir Mohammadi Nasab, Dylan Shah et al.
The manual design of soft robots and their controllers is notoriously challenging, but it could be augmented---or, in some cases, entirely replaced---by automated design tools. Machine learning algorithms can automatically propose, test, and refine designs in simulation, and the most promising ones can then be manufactured in reality (sim2real). However, it is currently not known how to guarantee that behavior generated in simulation can be preserved when deployed in reality. Although many previous studies have devised training protocols that facilitate sim2real transfer of control polices, little to no work has investigated the simulation-reality gap as a function of morphology. This is due in part to an overall lack of tools capable of systematically designing and rapidly manufacturing robots. Here we introduce a low cost, open source, and modular soft robot design and construction kit, and use it to simulate, fabricate, and measure the simulation-reality gap of minimally complex yet soft, locomoting machines. We prove the scalability of this approach by transferring an order of magnitude more robot designs from simulation to reality than any other method. The kit and its instructions can be found here: https://github.com/skriegman/sim2real4designs
13.5NEDec 15, 2023
Classical Sorting Algorithms as a Model of Morphogenesis: self-sorting arrays reveal unexpected competencies in a minimal model of basal intelligenceTaining Zhang, Adam Goldstein, Michael Levin
The emerging field of Diverse Intelligence seeks to identify, formalize, and understand commonalities in behavioral competencies across a wide range of implementations. Especially interesting are simple systems that provide unexpected examples of memory, decision-making, or problem-solving in substrates that at first glance do not appear to be complex enough to implement such capabilities. We seek to develop tools to help understand the minimal requirements for such capabilities, and to learn to recognize and predict basal forms of intelligence in unconventional substrates. Here, we apply novel analyses to the behavior of classical sorting algorithms, short pieces of code which have been studied for many decades. To study these sorting algorithms as a model of biological morphogenesis and its competencies, we break two formerly-ubiquitous assumptions: top-down control (instead, showing how each element within a array of numbers can exert minimal agency and implement sorting policies from the bottom up), and fully reliable hardware (instead, allowing some of the elements to be "damaged" and fail to execute the algorithm). We quantitatively characterize sorting activity as the traversal of a problem space, showing that arrays of autonomous elements sort themselves more reliably and robustly than traditional implementations in the presence of errors. Moreover, we find the ability to temporarily reduce progress in order to navigate around a defect, and unexpected clustering behavior among the elements in chimeric arrays whose elements follow one of two different algorithms. The discovery of emergent problem-solving capacities in simple, familiar algorithms contributes a new perspective to the field of Diverse Intelligence, showing how basal forms of intelligence can emerge in simple systems without being explicitly encoded in their underlying mechanics.
5.1NCNov 22, 2024
Bio-inspired AI: Integrating Biological Complexity into Artificial IntelligenceNima Dehghani, Michael Levin
The pursuit of creating artificial intelligence (AI) mirrors our longstanding fascination with understanding our own intelligence. From the myths of Talos to Aristotelian logic and Heron's inventions, we have sought to replicate the marvels of the mind. While recent advances in AI hold promise, singular approaches often fall short in capturing the essence of intelligence. This paper explores how fundamental principles from biological computation--particularly context-dependent, hierarchical information processing, trial-and-error heuristics, and multi-scale organization--can guide the design of truly intelligent systems. By examining the nuanced mechanisms of biological intelligence, such as top-down causality and adaptive interaction with the environment, we aim to illuminate potential limitations in artificial constructs. Our goal is to provide a framework inspired by biological systems for designing more adaptable and robust artificial intelligent systems.
What Lives? A meta-analysis of diverse opinions on the definition of lifeReed Bender, Karina Kofman, Blaise Agüera y Arcas et al.
The question of "what is life?" has challenged scientists and philosophers for centuries, producing an array of definitions that reflect both the mystery of its emergence and the diversity of disciplinary perspectives brought to bear on the question. Despite significant progress in our understanding of biological systems, psychology, computation, and information theory, no single definition for life has yet achieved universal acceptance. This challenge becomes increasingly urgent as advances in synthetic biology, artificial intelligence, and astrobiology challenge our traditional conceptions of what it means to be alive. We undertook a methodological approach that leverages large language models (LLMs) to analyze a set of definitions of life provided by a curated set of cross-disciplinary experts. We used a novel pairwise correlation analysis to map the definitions into distinct feature vectors, followed by agglomerative clustering, intra-cluster semantic analysis, and t-SNE projection to reveal underlying conceptual archetypes. This methodology revealed a continuous landscape of the themes relating to the definition of life, suggesting that what has historically been approached as a binary taxonomic problem should be instead conceived as differentiated perspectives within a unified conceptual latent space. We offer a new methodological bridge between reductionist and holistic approaches to fundamental questions in science and philosophy, demonstrating how computational semantic analysis can reveal conceptual patterns across disciplinary boundaries, and opening similar pathways for addressing other contested definitional territories across the sciences.
7.8AIMay 5, 2025
Giving Simulated Cells a Voice: Evolving Prompt-to-Intervention Models for Cellular ControlNam H. Le, Patrick Erikson, Yanbo Zhang et al.
Guiding biological systems toward desired states, such as morphogenetic outcomes, remains a fundamental challenge with far-reaching implications for medicine and synthetic biology. While large language models (LLMs) have enabled natural language as an interface for interpretable control in AI systems, their use as mediators for steering biological or cellular dynamics remains largely unexplored. In this work, we present a functional pipeline that translates natural language prompts into spatial vector fields capable of directing simulated cellular collectives. Our approach combines a large language model with an evolvable neural controller (Prompt-to-Intervention, or P2I), optimized via evolutionary strategies to generate behaviors such as clustering or scattering in a simulated 2D environment. We demonstrate that even with constrained vocabulary and simplified cell models, evolved P2I networks can successfully align cellular dynamics with user-defined goals expressed in plain language. This work offers a complete loop from language input to simulated bioelectric-like intervention to behavioral output, providing a foundation for future systems capable of natural language-driven cellular control.
9.4LGSep 22, 2025
Equilibrium flow: From Snapshots to DynamicsYanbo Zhang, Michael Levin
Scientific data, from cellular snapshots in biology to celestial distributions in cosmology, often consists of static patterns from underlying dynamical systems. These snapshots, while lacking temporal ordering, implicitly encode the processes that preserve them. This work investigates how strongly such a distribution constrains its underlying dynamics and how to recover them. We introduce the Equilibrium flow method, a framework that learns continuous dynamics that preserve a given pattern distribution. Our method successfully identifies plausible dynamics for 2-D systems and recovers the signature chaotic behavior of the Lorenz attractor. For high-dimensional Turing patterns from the Gray-Scott model, we develop an efficient, training-free variant that achieves high fidelity to the ground truth, validated both quantitatively and qualitatively. Our analysis reveals the solution space is constrained not only by the data but also by the learning model's inductive biases. This capability extends beyond recovering known systems, enabling a new paradigm of inverse design for Artificial Life. By specifying a target pattern distribution, we can discover the local interaction rules that preserve it, leading to the spontaneous emergence of complex behaviors, such as life-like flocking, attraction, and repulsion patterns, from simple, user-defined snapshots.
3.3AISep 12, 2025
ZapGPT: Free-form Language Prompting for Simulated Cellular ControlNam H. Le, Patrick Erickson, Yanbo Zhang et al.
Human language is one of the most expressive tools for conveying intent, yet most artificial or biological systems lack mechanisms to interpret or respond meaningfully to it. Bridging this gap could enable more natural forms of control over complex, decentralized systems. In AI and artificial life, recent work explores how language can specify high-level goals, but most systems still depend on engineered rewards, task-specific supervision, or rigid command sets, limiting generalization to novel instructions. Similar constraints apply in synthetic biology and bioengineering, where the locus of control is often genomic rather than environmental perturbation. A key open question is whether artificial or biological collectives can be guided by free-form natural language alone, without task-specific tuning or carefully designed evaluation metrics. We provide one possible answer here by showing, for the first time, that simple agents' collective behavior can be guided by free-form language prompts: one AI model transforms an imperative prompt into an intervention that is applied to simulated cells; a second AI model scores how well the prompt describes the resulting cellular dynamics; and the former AI model is evolved to improve the scores generated by the latter. Unlike previous work, our method does not require engineered fitness functions or domain-specific prompt design. We show that the evolved system generalizes to unseen prompts without retraining. By treating natural language as a control layer, the system suggests a future in which spoken or written prompts could direct computational, robotic, or biological systems to desired behaviors. This work provides a concrete step toward this vision of AI-biology partnerships, in which language replaces mathematical objective functions, fixed rules, and domain-specific programming.
Scale invariant robot behavior with fractalsSam Kriegman, Amir Mohammadi Nasab, Douglas Blackiston et al.
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 exhibit self similar behavior at different scales, we hypothesize that there may exist robot designs that have the same property. Here we demonstrate that this is indeed the case for some, but not all, modular soft robots: there are robot designs that exhibit a desired behavior at a small size scale, and if copies of that robot are attached together to realize the same design at higher scales, those larger robots exhibit similar behavior. We show how to find such designs in simulation using an evolutionary algorithm. Further, when fractal attachment is not assumed and attachment geometries must thus be evolved along with the design of the base robot unit, scale invariant behavior is not achieved, demonstrating that structural self similarity, when combined with appropriate designs, is a useful path to realizing scale invariant robot behavior. We validate our findings by demonstrating successful transferal of self similar structure and behavior to pneumatically-controlled soft robots. Finally, we show that biobots can spontaneously exhibit self similar attachment geometries, thereby suggesting that self similar behavior via self similar structure may be realizable across a wide range of robot platforms in future.
3.3NCDec 9, 2019
Modeling somatic computation with non-neural bioelectric networksSantosh Manicka, Michael Levin
The field of basal cognition seeks to understand how adaptive, context-specific behavior occurs in non-neural biological systems. Embryogenesis and regeneration require plasticity in many tissue types to achieve structural and functional goals in diverse circumstances. Thus, advances in both evolutionary cell biology and regenerative medicine require an understanding of how non-neural tissues could process information. Neurons evolved from ancient cell types that used bioelectric signaling to perform computation. However, it has not been shown whether or how non-neural bioelectric cell networks can support computation. We generalize connectionist methods to non-neural tissue architectures, showing that a minimal non-neural Bio-Electric Network (BEN) model that utilizes the general principles of bioelectricity (electrodiffusion and gating) can compute. We characterize BEN behaviors ranging from elementary logic gates to pattern detectors, using both fixed and transient inputs to recapitulate various biological scenarios. We characterize the mechanisms of such networks using dynamical-systems and information-theory tools, demonstrating that logic can manifest in bidirectional, continuous, and relatively slow bioelectrical systems, complementing conventional neural-centric architectures. Our results reveal a variety of non-neural decision-making processes as manifestations of general cellular biophysical mechanisms and suggest novel bioengineering approaches to construct functional tissues for regenerative medicine and synthetic biology as well as new machine learning architectures.
Automated shapeshifting for function recovery in damaged robotsSam Kriegman, Stephanie Walker, Dylan Shah et al.
A robot's mechanical parts routinely wear out from normal functioning and can be lost to injury. For autonomous robots operating in isolated or hostile environments, repair from a human operator is often not possible. Thus, much work has sought to automate damage recovery in robots. However, every case reported in the literature to date has accepted the damaged mechanical structure as fixed, and focused on learning new ways to control it. Here we show for the first time a robot that automatically recovers from unexpected damage by deforming its resting mechanical structure without changing its control policy. We found that, especially in the case of "deep insult", such as removal of all four of the robot's legs, the damaged machine evolves shape changes that not only recover the original level of function (locomotion) as before, but can in fact surpass the original level of performance (speed). This suggests that shape change, instead of control readaptation, may be a better method to recover function after damage in some cases.