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A GENERAL THEORY OF OXYGEN TOXICITY IN MAN* D. R. SHANKLIN, M.D.f Implicit in current biomedical thinking is the assumption that oxygen exchange occurs in a steady state ofthe external environment. While this maybe truefor practical purposes for the comparatively brief life span of any individual animal or person, it is demonstrably untrue for the panorama of evolution and particularly for those species recendy emergent. This hypothecationwillattempta fusion ofpresently available information on the evolution of atmospheric oxygen, human embryogenesis, and certain seeming paradoxes in a number ofanimal species, as viewed in the light ofour own researches [i]. The relation ofthese matters to adaptation to extrauterinelife in general, and to hyaline membrane disease in particular , is emphasized. In a series ofrecent papers, the late L. V. Berkner and Professor L. C. Marshall of the Southwest Center for Advanced Studies, Dallas, Texas, have formulated a definitive model ofthe oxygenic evolution of the atmosphere ofthis planet [2-6]. Since, as they ably point out, there is much evidence from the evolution of living organisms with implications for oxygenic evolution, and vice versa, it is seemly that we here abstract the Berkner-Marshall model with reference to some of the major sources of evidence and hypothecation. The solid primordial earth was probably without significant atmosphere . Principal among the evidences for this is the marked discordance between the low terrestrial concentrations and the much higher cosmic abundance ofthe rare gases [6-9]. These workers have concluded that the * This is the second part of a two-part paper, "On the Pulmonary Toxicity of Oxygen." Part r, "The relationship oftotal pressure and oxygen content to the effect ofoxygen on the lung," will bepublished in Laboratory Investigation [i], Supported by grants from the John A. Hartford Foundation , New York. t Professor ofobstetrics and gynecology and ofpathology, Chicago Lying-in Hospital, Pritzker School ofMedicine, University ofChicago. 80 D. R. Shanklin · Oxygen Toxicity in Man Perspectives in Biology and Medicine · Autumn 1969 earth lost the greater share ofthe gases during the agglomeration ofcomponent planetesimals [io]. Thus, Berkner and Marshall [3] agree with Fesenkov [11] that thepresent-day atmosphere isa secondary or evolutionary phenomenon. A confirmation ofthis exists in part in the calculation that the present-day supply ofAr*0 can be accounted for by its origin from K40 through radioactive decay over a period of approximately 5 X 10» years, a figure consistent with the age ofthe earth [12]. Examination ofthe physical chemistry ofthe complex compounds that make up a major share ofthe surface ofthe earth has led to the conclusion that the crust was not substantially molten at any one time [12-14]. Accordingly , large quantities ofgases are chemically bound in various ways. Growth ofthe initial atmosphere and oceans from volcanic gas discharge probably occurred over a very long period of time [8, 13-17]. Volcanic effluvient is predominandy water vapor, carbon dioxide, nitrogen, and sulfur dioxide, with lesser amounts of SO3, H3, Cl3, H3S, CO, HF, HBr, CH4, HCl, and NH3 [16]. Thus, the primitive atmosphere was without significant oxygen. This conclusion is confirmed by studies of the molecular evolution of life [18-27]. Since it is probable that photoexcitation played a major role in the synthesis ofearly compounds [28], a detailed consideration ofthe relation ofatmospheric components, ultraviolet radiation, and early cellular components was undertaken by Berkner and Marshall [2, 3]. Indeed, the absence ofoxygen in a free state is probably a necessity for the evolution ofliving things asweknowthem. Abelsonhas shown thatamino acids are stable at moderate temperature in the absence ofoxygen [29]; further, oxygen is a poison to nuclei ofpresent-day cells [27]. Since there is much oxygen in the atmosphere today, the general principle of uniformitarianism as applied to the atmosphere must be abandoned in favor ofan evolutionary view ofthe problem. This is supplied by the Berkner-Marshall model. The details ofultraviolet absorption in relation to oxygen accumulation and the evolution ofliving things are too intricate to relate here comprehensively . The conclusions ofBerkner and Marshall with reference to electromagnetic absorption are important to an understanding of oxygenic evolution. The fact thatonly oxygen and ozone significandy absorb radiation with wavelengths above 2,000 Â is ofgreat importance. Photochemical dissociation of water occurs principally in the...

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