Stable isotopes from Earth science to bedside medicine: beyond tracers and toward mechanistic biomarkers in medical oncology

Abstract Stable isotopes are non-radioactive variants of the same element whose small mass differences produce predictable effects in chemical and biological systems. While medicine has mainly used the administration of enriched stable isotopes as tracers of physiological function, the natural sciences developed stable-isotope ratios into robust measures of source, transformation, and underlying mechanism across Earth and life history. This analytical power – that often goes beyond conventional concentration-based assays – emerged through advances in isotope theory, mass spectrometry, but perhaps most importantly also globally shared reference systematics. Here, we review that trajectory and argue that medicine is positioned for a similar shift, as new computational and analytical tools make isotope analysis increasingly compatible with clinical throughput. In this shift, some natural isotope variation may serve as mechanistic biomarkers of physiology and disease. Integrated with multiomics and machine learning, stable isotopes could support earlier detection, improved risk stratification, and personalized care, particularly in cancer.