Please go to the College of Arts & Sciences page for a lay summary of our work.

Atom-first biology borrows from bio-inorganic chemistry as well as geochemistry, and is inspired by the life’s work of RJP Williams. It operates on two axioms: (a) biomass is the result of active accumulation of ~20 elements, and (b) energy is required to concentrate elements. This perspective differs from the nucleotide-first (e.g., molecular and cellular biology) as well as its progenitor, the organism-first (e.g., environmental biology) approaches in mainstream biology. As a classically trained organismal biologist, and ~20 years of learning, I respectfully submit that an organism-first biology, performed by organisms (i.e., us) is colored by intuition, often obscuring the simplest explanation (i.e., Occam’s Razor) to most foundational biological puzzles. Further, post-genomic era discoveries have inordinately complicated the very units of classical biological observation (e.g., organism in the context of the microbiome). Such issues are in addition to longstanding problems related to definitions of entities central to biology (e.g., species). It is prudent to approach biological problems in other ways, where entities are clearly defined. Atoms of biogenic elements, at least in the context of biology, are such entities. Technological advancements in the rapid and precise measurement of elements, as well as the rules discovered by chemists enable unprecedented observational and inferential abilities of biological and ecological systems. That said, atom-first biology is neither atom-scale nor chemistry. While universal chemical rules are handy, and atom-scale models are becoming ever proficient at explaining biocomplexity (e.g., Singharoy et al. 2019), such models are too detailed to scale up to make sense of higher order biology, the realm beyond clean-chemistry predictions. As such, we are not chemists of yore. We are biologists of the future, harnessing new senses afforded by technological breakthroughs to explore biodiversity at the lowest level of organization. We celebrate doubt of the known as a driving force of scientific inquiry. Doubt does not mean disrespect.

The material composition of biomass (or a specific biostructure) is the point of departure for an exercise in atom-first biology (Beagle 2.0 will certainly have an elemental analyzer, like ChemCam on Curiosity). Viewing the elemental composition of a growing E. coli (Figure 1) from a biogeochemical perspective, the common stoichiometry of protoplasmic life, and fundamental anabolic processes such as protein synthesis become readily apparent (e.g., Figure 2). Consequently, we know much about the relationship between biology and bulk elements (C, H, N, O, P, S; Figure 3) because they form the backbone of biochemicals. Agricultural demand for these elements has altered the cycles of these elements, impacting the functioning of non-target ecosystems and the ecology and evolution of biota in the Anthropocene.

But knowing the relationships between bulk elements and biology is not very informative (Jeyasingh et al. 2014). It is time to make systemic headway, and move away from modular thought (Sprengel 1838; Leibig 1855). Briefly, let us assume a cell has everything to make a protein, and it does. An immediate and important consequence of this event is not the typical biological inference (e.g., growth, fitness), rather it is the demand for an anion to balance the negative charge added by the new protein. This function is performed by the major ions (sodium, magnesium, potassium, calcium; Figure 3), else, growth will not happen. Map on to this another chemical reality: major ions vary orders of magnitude in supply depending on geology (Figures 4, 5). And, finally, trace metals (e.g., manganese, iron, copper, zinc; Figure 3) perform biochemical catalysis, the precise nature of which is partly determined by the metal which is added to immature proteins. The supplies of these trace metals also vary several orders of magnitude (Figures 4, 5), and these cycles are experiencing rapid changes of large magnitude (Penuelas et al. 2022).

How does the system of elements respond to perturbations? Even in experimentally enforced severe single nutrient limitation, biomass is constrained by imbalances in multiple elements, other than the limiting one (Figure 6; Jeyasingh et al. 2020; Ipek & Jeyasingh 2021). Moreover, populations adapt to mitigate such ionome-wide imbalances (Jeyasingh et al. 2023). Ionome-wide adjustments arise from simple chemical rules outside the organism (e.g., Gustafsson 2018) as well as complex physiological responses (e.g., Jeyasingh et al. 2011; Roy Chowdhury et al. 2015). But we know very little about the behavior of this system, and is a central thrust of current work in the lab. These systems-biological observations has much to contribute toward a predictive understanding of traits (e.g., growth rate, size, ornaments) at the organismal level (e.g., Goos et al. 2016; 2017; Sherman et al. 2017; 2021; Rudman et al. 2019), and demographics (e.g., Lind & Jeyasingh 2018; Jeyasingh & Pulkkinen 2019), trophic interactions (e.g., Roy Chowdhury & Jeyasingh 2016; Jeyasingh et al. 2020), and productivity (e.g., Prater et al. 2020; Lind et al. 2021) at the supra-organismal levels of biological organization. Given the challenges of replication and prediction in organism-first biology, particularly in natural (beyond clean chemistry) conditions, atom-first biology is one expedition we owe the next generation of biologists.

We employ theory, lab experiments, field experiments & surveys, and are set up to quantify the elemental composition of cells, organs, individuals, populations, and communities. Positions for undergraduate, graduate, and postdoctoral research are available or can be developed. Email Puni (puni.jeyasingh@okstate.edu).

Figure 5: Geomorphic regions of Oklahoma varying in age and chemical composition. Curtis et al. 2008.

Gustafsson, J. P. (2018). Visual MINTEQ 3.1. https://vminteq.lwr.kth. se/.

Liebig J (1855) Principles of agricultural chemistry. Dowden, Hutchinson & Ross, London.

McFarland, B. 2016. A World From Dust: How the Periodic Table Shaped Life (Illustrated edition.). Oxford University Press.

Milo R, Phillips R (2015) Cell Biology by the Numbers. Garland Science.

Penuelas, J., J. Sardans, and J. Terradas. (2022). Increasing divergence between human and biological elementomes. Trends in ecology & evolution 0.

Singharoy, A., C. et al. (2019). Atoms to Phenotypes: Molecular Design Principles of Cellular Energy Metabolism. Cell 179:1098–1111.e23.

Sprengel C (1838) The science of cultivation and soil amelioration. Immanuel Muller Co., Leipzig, Germany.

Sterner RW, Elser JJ (2002) Ecological Stoichiometry. Princeton University Press.

Unreferenced citations are from our group: please see Publications.