Research

Atom-first biology draws from bioinorganic chemistry and biogeochemistry, and is inspired by ecological stoichiometry, ionomics, and the life’s work of R.J.P. Williams, particularly as synthesized in his co-authored volumes written during retirement. The deeper intellectual lineage traces to Lotka’s physical biology.

Why an atom-first perspective?

Mainstream biology has largely developed along two trajectories.
 

Organism-first biology, including much of environmental and ecological biology, treats organisms as the primary units of observation.
 

Nucleotide-first biology, including molecular and cellular biology, places informational macromolecules at the foundation of explanation.

Atom-first biology differs from both approaches by treating material composition as the point of departure.

As a classically trained organismal biologist, and after nearly two decades of learning across disciplines, I respectfully submit that organism-first biology, performed by organisms (ourselves), is often colored by intuition. This intuition can obscure key observations and explanations relevant to persistent biological and ecological puzzles.

Why biological entities complicate inference

• Post-genomic discoveries have complicated classical biological entities. The organism itself is increasingly difficult to define, particularly in the context of microbiomes, symbioses, and ubiquitous local adaptation. 

• These challenges add to longstanding issues surrounding central biological concepts such as species definitions and individuality, complicating replication and prediction.

• Atoms of biogenic elements, by contrast, are clearly defined entities. In the context of biology, they provide stable units for observation and inference.

Why now: measurement and chemical rules

• Recent technological advances allow rapid and precise measurement of elemental composition across environments and levels of biological organization.

• At the same time, centuries of work in chemistry have established rules governing bonding, charge balance, coordination, and speciation.

• Together, these advances enable new modes of biological observation and inference.

• Atom-first biology is not atom-scale modeling, nor is it chemistry. While atomistic models can explain biocomplexity (e.g., Singharoy et al. 2019), they are not intended to scale directly to higher-order biological questions. As emphasized by Lawton (1996), there is much to learn from natural patterns.

Elemental composition as the starting point

• The material composition of biomass, or of a specific biological structure, is the starting point for atom-first inquiry.

• Viewed from a biogeochemical perspective, the molecular composition of a growing Escherichia coli (Figure 1) reveals the common stoichiometry of protoplasmic life (Figure 2) and highlights fundamental anabolic processes such as protein synthesis.

• This perspective explains why we know much about relationships between biology and bulk elements (C, H, N, O, P, S; Figure 3), and why human alteration of their cycles has profoundly affected ecosystems in the Anthropocene.

Beyond bulk elements and modular thinking

• Relationships between bulk elements and biology are not sufficiently informative on their own (Maret 2022). Systemic progress requires moving beyond modular frameworks rooted in classical nutrient limitation (Sprengel 1838; Liebig 1855). 

• For example, protein synthesis introduces negative charge that must be balanced by major cations such as sodium, magnesium, potassium, and calcium. 

• Without charge balance, growth functions are altered. Major ions and trace metals vary by orders of magnitude in environmental supply due to geology (Figure 4, 5), and these cycles are changing rapidly in the Anthropocene (Peñuelas et al. 2022).

How do elemental systems behave?

• Even under experimentally enforced single-nutrient limitation, biomass is constrained by ionome-wide imbalances rather than the nominally limiting element (Figure 6; Jeyasingh et al. 2020; Ipek & Jeyasingh 2021).

• Populations adapt to mitigate these imbalances in replicated ways (Jeyasingh et al. 2023). Such responses emerge from chemical rules operating outside organisms (e.g., Gustafsson 2018) as well as physiological regulation within organisms (e.g., Jeyasingh et al. 2011; Roy Chowdhury et al. 2015).

• Despite this, we know little about the behavior of elemental systems as integrated wholes, a central motivation of current work in the lab (e.g., Prater et al. 2024).

Implications across biological scales

• Ionome-wide perspectives inform understanding of traits, demographics, trophic interactions, and ecosystem productivity (e.g., Lind & Jeyasingh 2018; Prater et al. 2020; Lind et al. 2021).

• Given challenges in replication and prediction in organism-first biology, particularly under natural conditions, atom-first biology represents one expedition we owe the next generation of biologists.

Our approach

• We quantify elemental composition of environments (e.g., soil, water, diet) and biomass across scales, from cells and organs to populations and communities. 

• We combine theory, laboratory experiments, field experiments, and surveys to glean chemical mechanisms underlying a variety of biological and ecological phenomena. 

Elemental measurements and instrumentation

Ionomic datasets are technically demanding, with data quality depending as much on sample preparation, contamination control, calibration, drift monitoring, and matrix effects as on the instrument itself. For this reason, we strongly recommend that multi-element measurements (e.g., ICP-MS, ICP-OES/AES, IC, CHNS) be conducted in laboratories that specialize in elemental analysis rather than treated as routine add-ons. Samples generated within our lab are analyzed either in house or through established collaboration with a specialist facility, Cove Sciences, depending on the element panel and matrix. High-quality elemental data are a prerequisite for meaningful biological inference, and our role is typically to advise on measurement strategy and to interpret such datasets explicitly as compositional systems.

References:

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

Lawton J (1996) Patterns in ecology. Oikos 75: 145-147.

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

Maret W (2022) The quintessence of metallomics: a harbinger of a different life science based on the periodic table of the bioelements. Metallomics 14(8):mfac051. 

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

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

Penuelas J. Sardans J,  Terradas J (2022) Increasing divergence between human and biological elementomes. Trend Ecol Evol 37: P935-938. 

Singharoy A, 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.

Unreferenced citations are from our group: please see Google Scholar