Medical applications of isotope metallomics

Abstract

One may wonder how a paper discussing medical applications of metal isotopes got lost in a review journal dedicated to mineralogy and geochemistry. The justifications are multiple. First, the coming of age of metal isotopic analysis in the mid ‘90s is largely due to the analytical creativity of the geochemical community and to corporate technical skills allowing the rise of new technologies. Second, many concepts, which can be imbedded in quantitative models testable from their predictions, are common to geochemistry, biochemistry, physiology, and nutrition: a cell, with its organelles, a body with its organ and body fluids, are systems liable to treatments similar to those used to model a lake, the ocean–atmosphere, and the mantle–crust systems. Of course, time scales and length scales differ, the complexity of biology is immense compared to that of the mineral world. Geological systems lack the hallmarks of life, genes and cell signaling. In spite of the overall complexity of the biological systems, pathways, kinetics, and chemical dynamics are better understood than their counterpart in earth sciences. Like in many fields of engineering, comparing the records of inputs and outputs is a powerful tool to identify the internal ‘knobs’ controlling a given system and learn how to tweak them. Third, although some of the most sophisticated techniques such as ab initio calculations of molecular configurations, energetics, and isotopic properties are still limited to molecules with less than a few dozens of atoms, the time is getting closer to when simulations of large molecules will become available for application to ‘real’ proteins with large molecular weights. The present article reviews some of the basic features of what is now known as Metallomics and the preliminary applications of stable isotopes to some medical cases, a discipline for which we suggest the simple term of Isotope Metallomics . …