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In his treatise on the psychology of science, Abraham H. Maslow noted that when the only tool you have is a hammer you tend to think of every problem as a nail (1). One group that appears to personify this principle more so than others are the hi-tech–minded practitioners of applied analytical sciences, in particular those interested in disease biomarkers. Depending on the class of molecules targeted for specific analyses, for example nucleic acids, proteins, or small molecules, the biomarker field can be categorized in subspecialties such as genomics, proteomics, and metabolomics, to just name the most prominent ones. It is not surprising that each specialty has its advocates, often using arguments based solely on available expertise. A telling example of the hammer-and-nail theory can occasionally be witnessed at proteomics gatherings when the need is stressed to prioritize analysis of proteins because “they carry out all the work” in a cell whereas a gene/transcript is merely a genetic blueprint. True, except that in the protein biomarker field the emphasis has been almost exclusively on measuring disease-related changes in protein concentrations and modifications, using immunohistochemistry (IHC)2 or mass spectrometry (MS), and not on differential biological activities.Prospective usage in blood-based testing has been one of the key criteria that guided most searches for the perfect disease biomarkers during the past decennia. Aside from a few early hits, such as CA125 and CEA, it does not appear that said IHC/MS approach has been much of a success (2), mainly because the complexity of the blood proteome precludes detection at the low– and sub–nanogram-per-milliliter …

Mass-Encoded, Synthetic Biomarkers and Multiplexed Urinary Monitoring: New Frontiers in Disease Monitoring