Review | Fundamental Constraints to the Logic of Living Systems

Introduction

As early as Schrödinger’s reflections on life’s thermodynamic constraints, and later with the advent of systems biology, researchers began emphasizing the interplay between contingent evolutionary pathways and overarching constraints imposed by physical laws. Despite remarkable strides in understanding, the complexity of biological systems repeatedly resisted exhaustive theoretical reduction. Life’s dynamic adaptability and structural organization continued to challenge frameworks rooted in purely mechanistic or linear explanations. This has brought with it a skeptical feeling towards mechanism, where any possible formalization of the phenomenon of life, together with its consequences, has been questioned.

In the paper Fundamental Constraints to the Logic of Living Systems the authors look for advancing the mechanistic perspective by identifying the intrinsic limitations that define the architecture of living systems. From thermodynamic boundaries to the linearity of molecular information carriers and the threshold nature of cognitive architectures, the authors argue that life’s design space is shaped by deep constraints—both structural and functional. In this way, the paper illuminates how these constraints are simultaneously universal and emergent, limiting the range of possible outcomes in both evolutionary trajectories and artificial life design.

In this review, I will examine the central themes of this work, focusing on the role of convergence, contingency, and the universal principles that govern the organization of life. By dissecting the constraints outlined in the paper, I aim to highlight their implications for understanding life as a complex adaptive system, and explore the theoretical avenues proposed for future inquiry into the logic of living matter. At the same time, I will address conceptual and narrative gaps that I consider important for the understanding of the phenomenon of life, many of them previously pointed out by Luis M. Rocha. Thanks to him, I had the privilege of reading a draft of this paper prior to its publication.

Living systems as info-thermodynamic machines

The introduction effectively sets the stage by highlighting the tension between evolutionary path-dependence and universal constraints. The authors frame their inquiry within the broader context of astrobiology and synthetic biology, emphasizing the need to identify principles that define life irrespective of its origin. However, while the paper references Gould’s historical contingency and Monod’s unpredictability, it could delve deeper into the role of enabling constraints—those that not only limit but also facilitate the emergence of specific biological phenomena. For instance, while thermodynamics and gravity constrain all physical systems, living systems uniquely exploit these constraints to achieve autonomy and self-organization. This distinction underpins much of the subsequent discussion but warrants more explicit acknowledgment upfront.

The section on thermodynamic constraints presents living systems as thermodynamic engines, emphasizing their entropy-reduction capabilities and their coupling to environmental energy sources. The authors argue that life uniquely achieves thermodynamic autonomy by constructing and maintaining boundaries that regulate internal conditions. While this framing is insightful, it risks overstating the universality of thermodynamic constraints without sufficiently distinguishing between abiotic and biotic systems. Stating that life follows thermodynamic laws is tautological; all material systems do. The critical question here is whether thermodynamics provides enabling constraints that distinguish life from abiotic dissipative structures.

For example, hurricanes and Bénard cells reduce entropy and exhibit cycles but lack the ability to construct the engines that sustain them. Biological systems, by contrast, actively construct and repair their boundaries, enabling autonomy and evolutionary adaptation. Moreover, the focus on boundaries as defining features of thermodynamic engines could be reconsidered. Organisms often operate as open networks, exchanging energy and genetic information with their environment. Generally speaking, the boundaries of thermodynamic engines do not necessarily align with the boundaries of organisms, which are defined by more complex networks of interactions. This openness challenges traditional definitions of organismal autonomy and aligns with concepts like the pan-genome, where an organism’s effective genome extends beyond its cellular boundaries.

The authors’ exploration of linear information carriers highlights the evolutionary advantages of one-dimensional molecular chains like DNA. This discussion connects Schrödinger’s conceptualization of genetic information with contemporary insights into the thermodynamic efficiency of molecular computation. However, Schrödinger’s predictions were limited by his failure to recognize the dual roles of genetic information: as passive memory and as active instructions for construction. On the other hand, Von Neumann’s model of active and passive informational modes addresses this gap, emphasizing the separation of these roles as a prerequisite for evolution. This distinction, overlooked in the paper, is essential for understanding the robustness and evolvability of biological systems.

Cells, holobionts and beyond

Their discussion on cells as minimal units of life draws heavily on Von Neumann’s Universal Constructor, framing cellular life as the intersection of self-replication, compartmentalization, and information processing. This framing effectively connects abstract computational models with the material realities of living systems. However, Von Neumann’s goal was not merely to model self-replication but to explore how systems could accumulate complexity in defiance of the second law of thermodynamics. This distinction is crucial for understanding the evolutionary potential of living systems. By focusing on self-replication, the paper risks conflating the implementation of Von Neumann’s theory with its broader implications for open-ended evolution.

The section on multicellularity examines the constraints shaping the transition to multicellular life, emphasizing the role of life cycles, group selection, and developmental processes. The authors highlight the universal challenge of cheaters and the evolutionary mechanisms that stabilize cooperation. This discussion aligns well with the comments on the role of ratcheting processes, which lock cells into group lifestyles, facilitating multicellular complexity. However, the paper could further explore the combinatorial power of gene regulatory networks and their role in enabling multicellular development. For example, the mapping of genotype to phenotype imposes constraints that both limit and enable the evolution of novel forms. This dual role of constraints warrants greater emphasis.

The exploration of cognitive networks focuses on the threshold-based logic of decision-making, drawing parallels between neurons, gene regulatory networks, and microbial quorum sensing. This section effectively demonstrates the convergence of design principles across biological scales. Nevertheless, the universality of discrete biological information processing could be emphasized even further. Threshold-based responses are not limited to neural systems but are fundamental to gene regulation, immune activation, and collective behavior. These examples illustrate the deep integration of analogue and digital computation in living systems, a theme that could unify the discussion across sections.

While the paper addresses evolution implicitly, it does not foreground it as a fundamental constraint on living systems. Darwin’s four axioms—organisms vary from one another, new variation appears from time to time, variation is passed from parent to offspring, and limited resources—are enabling constraints that make evolution inevitable on any material substrate. These axioms could provide a unifying framework for the discussion, connecting thermodynamics, information, and multicellularity to the broader logic of natural selection. Von Neumann’s unpacking of inheritance into active and passive modes complements Darwin’s framework, explaining how variation can be preserved and transmitted. The paper’s emphasis on constraints limiting the evolutionary search space could be expanded to include the enabling role of these constraints in shaping adaptive landscapes.

Conclusion

The paper’s ambition to identify universal constraints on living systems is commendable, but its focus on limitations could be balanced by a greater emphasis on enabling constraints. Constraints are not merely barriers but also scaffolds that shape the possibilities of life. By integrating insights from thermodynamics, information theory, and evolution, we can move closer to a general theory of life that transcends Earth’s biosphere. This synthesis must also account for the openness of biological systems, both in terms of information exchange (e.g., pan-genomics) and thermodynamic autonomy. Living systems are not isolated engines but dynamic networks embedded in broader ecological and evolutionary contexts. By reframing constraints as opportunities for innovation, we can better understand the logic of life and its potential manifestations beyond our biosphere.