







This year we celebrate the 150th anniversary of the law of mass action. This law is often assumed to have been “there” forever, but it has its own history, background, and a definite starting point. The law has had an impact on chemistry, biochemistry, biomathematics, and systems biology that is difficult to overestimate. It is easily recognized that it is the direct basis for computational enzyme kinetics, ecological systems models, and models for the spread of diseases. The article reviews the explicit and implicit role of the law of mass action in systems biology and reveals how the original, more general formulation of the law emerged one hundred years later ab initio as a very general, canonical representation of biological processes.
Global constraint principle for microbial growth laws | PNAS
Understanding complex living systems requires identifying universal phenomenological laws that are independent of species and molecular-biological ...

An attempt to explain category theory to biologists in 15 minutes | David Spivak
A Drive to Survive
Since 2005, Karl Friston's proposal that the principle of free energy minimization underpins the purposive behavior of living agents has evolved through thou...

The lost art of mathematical modelling
We provide a critique of mathematical biology in light of rapid developments in modern machine learning. We argue that out of the three modelling activities – (1) formulating models; (2) analysing models; and (3) fitting or comparing models to data – inherent to mathematical biology, researchers currently focus too much on activity (2) at the cost of (1). This trend, we propose, can be reversed by realising that any given biological phenomenon can be modelled in an infinite number of different ways, through the adoption of a pluralistic approach, where we view a system from multiple, different points of view. We explain this pluralistic approach using fish locomotion as a case study and illustrate some of the pitfalls – universalism, creating models of models, etc. – that hinder mathematical biology. We then ask how we might rediscover a lost art: that of creative mathematical modelling.
Are biological systems poised at criticality?
Many of life's most fascinating phenomena emerge from interactions among many elements--many amino acids determine the structure of a single protein, many genes determine the fate of a cell, many neurons are involved in shaping our thoughts and memories. Physicists have long hoped that these collective behaviors could be described using the ideas and methods of statistical mechanics. In the past few years, new, larger scale experiments have made it possible to construct statistical mechanics models of biological systems directly from real data. We review the surprising successes of this "inverse" approach, using examples form families of proteins, networks of neurons, and flocks of birds. Remarkably, in all these cases the models that emerge from the data are poised at a very special point in their parameter space--a critical point. This suggests there may be some deeper theoretical principle behind the behavior of these diverse systems.

Design in The Age of Biology: Shifting From a Mechanical-Object Ethos to an Organic-Systems Ethos
In the early twentieth century, our understanding of physics changed rapidly; now, our understanding of biology is undergoing a similar rapid change.
Biohub releases a world model of protein biology
Open AI models used for a wide range of scientific applications, including accelerating the design of therapeutic molecules.

Growth, metabolic partitioning, and the size of microorganisms
Population growth rate is a fundamental ecological and evolutionary characteristic of living organisms, but individuals must balance the metabolism devoted to biosynthesis and reproduction against the maintenance of existing structure and other functionality. Here we present a mathematical model that relates metabolic partitioning to the form of growth. The model captures the observed growth trajectory of single cells and individuals for a variety of species and taxa spanning prokaryotes, unicellular eukaryotes, and small multicellular eukaryotes. Our analysis suggests that the per-unit costs of biosynthesis and maintenance are conserved across prokaryotes and eukaryotes. However, the relative metabolic expenditure on growth and maintenance of whole organisms clearly differentiates taxa: prokaryotes spend an increasing fraction of their entire metabolism on growth with increasing cell size, whereas eukaryotes devote a diminishing fraction. These differences allow us to predict the minimum and maximum size for each taxonomic group, anticipating observed evolutionary life-history transitions. The framework provides energetic insights into taxonomic tradeoffs related to growth and metabolism and constrains traits that are important for size-structured modeling of microbial communities and their ecological and biogeochemical effects.

Agentic systems are adept at solving well-scoped, verifiable problems in computational biology
We introduce CompBioBench, a benchmark of 100 diverse tasks for evaluating agentic systems in computational biology. Unlike mathematics and programming, which more readily admit systematic verification, biological data are inherently noisy and open to interpretation.
Maximum power in evolution, ecology and economics
Ludwig Boltzmann suggested that natural selection was fundamentally a struggle among organisms for available energy. Alfred Lotka argued that organisms that capture and use more energy than their competition will have a selective advantage in the evolutionary process, i.e. the Darwinian notion of evolution was based on a fundamental, generalized energy principle. He extended this general principle from the energetics of a single organism or species to the energetics of entire energy pathways through ecosystems. Howard Odum and Richard Pinkerton, building on Lotka, extended this concept to ‘The maximum power principle’ and applied it to many biological and physical systems including human economies. We examine this history and how these ideas relate to concepts from other disciplines including philosophy. But there has been considerable confusion in understanding and applying these concepts which we attempt to resolve while providing various examples from routine life and discussing some unresolved issues. This article is part of the theme issue ‘Thermodynamics 2.0: Bridging the natural and social sciences (Part 2)’.

Import AI 459: AI oversight is difficult; scaling laws for protein folding models; and pricing the extinction risk of AI systems
Do you feel as though you are living in a revolution?

Two decades of functional–structural plant modelling: now addressing fundamental questions in systems biology and predictive ecology
AbstractBackground. Functional–structural plant models (FSPMs) explore and integrate relationships between a plant’s structure and processes that underlie

Bone metastasis treatment modeling via optimal control
Metastatic disease is a lethal stage of cancer progression. It is characterized by the spread of aberrant cells from a primary tumor to distant tissues like the bone. Several treatments are used to deal with bone metastases formation, but they are palliative since the disease is considered incurable. Computational and mathematical models are used to understand the underlying mechanisms of how bone metastasis evolves. In this way, new therapies aiming to reduce or eliminate the metastatic burden in the bone tissue may be proposed. We present an optimal control approach to analyze some common treatments for bone metastasis. In particular, we focus on denosumab treatment, an anti-resorptive therapy, and radiotherapy treatment which has a cell killing action. We base our work in a variant of an existing model introduced by Komarova. The new model incorporates a logistic equation in order to describe the bone metastasis evolution. We provide proofs of existence and uniqueness of solutions to the corresponding optimal control problems for each treatment. Moreover, we present some numerical simulations to analyze the effectiveness of both treatments when different interactions between cancer and bone cells occur. A discussion of the obtained results is provided.

Requisite variety and its implications for the control of complex systems
Recent work on the fundamental processes of regulation in biology (Ashby, 1956) has shown the importance of a certain quantitative relation called the law of requisite variety. After this relation had been found, we appreciated that it was related to a theorem in a world far removed from the biological—that of Shannon on the quantity of noise or error that could be removed through a correction-channel (Shannon and Weaver, 1949; theorem 10). In this paper I propose to show the relationship between the two theorems, and to indicate something of their implications for regulation, in the cybernetic sense, when the system to be regulated is extremely complex. Since the law of requisite variety uses concepts more primitive than those used by entropy, I will start by giving an account of that law.
Controlled Mold
A blog about fermentation, engineering, and cell-ag. We run wild experiments on microbes and try to eat them, all with the help of computers and math.