Inventor and innovator: cardiac troponin T.

Abstract

When I started my research fellowship in 1978 in Edgar Haber’s Lab at the MGH in Boston, blood testing for acute myocardial infraction (AMI) commonly employed CK- and CKMB-activity measurements, which were neither sensitive nor specific for AMI nor very useful for risk prediction. Research in Edgar Haber’s Lab was focused on antibody diversity and the use of antibodies as diagnostic and therapeutic tools. In this thrilling environment, we hypothesized in 1979 that cardiac sarcomere proteins, due to their high intracellular mass and their expression as tissue specific isoforms, may improve diagnosis of AMI if detected in blood by highly sensitive assays. The advent of the hybridoma technology for production of monoclonal antibodies (first reported by Köhler and Milstein in Nature 1975) opened new avenues for the predictive engineering of immuno-assays according to the affinity and epitope specificity of selected antibody molecules. Using preselected monoclonal antibodies, we engineered in 1980 a novel assay format (double sandwich assay) and used this sandwich assay modality to measure cardiac myosin light chains.1 Using this cardiac myosin light chain assay, we were the first to show that sarcomere biomarker outperform CKMB in risk prediction of chest pain patients and detection of AMI.2