In Vivo Detection of Free Radicals in Real Time by Low-Frequency Electron Paramagnetic Resonance Spectroscopy

During his studies on the properties of oxygen, Priestley (
1
) noted that this gas, an essential ingredient for life processes, appears to “burn out the candle of life too quickly.” More than two centuries would elapse, however, before this observation would be associated with Grubb�’s (
2
) accounts of redness and irritation on the hands of his workers testing X-ray tubes. By 1954, Gerschman et al. (
3
) suggested that free radicals were the common element linking the observed toxicity of oxygen to the harmful effects of ionizing radiation. The implication of this hypothesis seemed remote at that time. However, within a decade, the search for biologically generated free radicals would lead to the discovery of superoxide and an enzyme that attenuated cellular levels of this free radical (
4
,
5
). In the intervening years, free radicals have been recognized as common intermediates in cellular metabolism (
6
,
7
), found to play an essential role in host immune response (
8
) and demonstrated to regulate many essential physiologic functions (
9
).