Abstract
Oxygen, the diradical byproduct of photosynthesis from algae and plants, made possible the emergence of aerobic life beginning about 4 billion years ago. Along with the evolution of aerobic life processes came the consequence of oxygen toxicity and the necessity of the development of an antioxidant defense system by aerobic prokaryotes. Eukaryotes, both by inheriting and improving upon the first prokaryote defenses against the toxic reactive oxygen intermediate species (ROIs), have developed a multiplicity of ROI defense systems consisting of dietary nutrients and endogenously synthesized molecules ranging from the simple to the more complex enzymes, as in the nearly universal distribution of superoxide dismutase. Multicellular animal species have even used the toxic properties of oxygen in the evolution of their own defense systems against xenobiotic intruders in the respiratory burst of the cellular immune system. This historical account traces the discoveries and events of the free radical theory of oxygen toxicity first espoused by Rebecca Gerschman in 1954 and later confirmed by Irwin Fridovich with the confirmation of discovery of superoxide (O2 -) and superoxide dismutase in 1969. Along with these discoveries and the continuing refinement of the experimental data that continues to support the theoretical basis of the free radical theory, has come the realization that cancer and life's other degenerative diseases, including the aging process itself, may also be a consequence of an aerobic existence.