The evolution of biomedical EPR (ESR)

Since the first EPR/ESR spectrum of a paramagnetic substance was published over 70 years ago, the technical improvements did not occur until after/during World War II with the advent of radar technology. The approaches to biomedical problems started somewhat later with the real burst of activity starting after the birth of the spin label technique about 50 years ago. The applications to proteins, then membranes and nucleic acids, and later applications to cells and eventually in-vivo on small animals and now humans has led EPR/ESR to finally being recognized as a uniquely powerful technique in the toolbox of techniques probing macromolecules and their interactions, free radical biology and its eventual value as a diagnostic technique. This article gives an overview of EPR/ESR studies of biomedically related systems, including proteins and enzymes. It presents a very personal historical perspective, briefly reviews the origins of the technique and reflects on possible future directions. As with NMR, advances in molecular biology and technology drastically changed the nature and focus of the technique, particularly the site directed spin labeling method that has been invaluable in determining protein and macromolecular structure by both EPR and NMR.