The Chemiosmotic Hypothesis of Energy Coupling and the Path of Scientific Opportunity

THE CHEMIOSMOTIC HYPOTHESIS OF ENERGY COUPUNG AND THE PATH OF SCIENTIFIC OPPORTUNITY JOSEPHD. ROBINSON* Introduction The development of the chemioemotic hypothesis of energy coupling not only represents one of the most spectacular achievements in the contemporary flourishing of biochemistry, but the fortunes of this research program also provide a'notable opportunity for examining the evolution of scientific theories and the nature of the rivalries between them. From the initial formulations by Peter Mitchell in 1961 [1-3] to his receiving the Nobel Prize for chemistry in 1978, reaction to the chemiosmotic hypothesis ranged from neglect to criticism to acclaim. This course, reflecting the elaboration and exploitation of a new research program as well as its conflicts with an established rival, can thus serve to exemplify the practice of scientific research and to illuminate thejudgments and issues involved. Factors influencing dieory change and the resolution of scientific conflicts have been vigorously if variously sought, with attention focused chiefly on the physical sciences and with invocations of cumulative changes, progressive research programs, falsifications, and revolutions [4, 5]. Applying such criteria to the biological sciences may seem even more forbidding, since in the current developmental stages of these sciences the descriptions of phenomena are at least as prominent as the formulations of generalized theories and laws. The search for broad principles underlying concept transformations and theory choices may The author thanks Dr. Richard Cross for his critical comments. An earlier version ofthis paper was presented to the Syracuse Consortium for the Cultural Foundations of Medicine, Syracuse, N.Y., November 30, 1981. Support for research on membrane transport was provided by National Institutes of Health grant NS-05430.»Department of Pharmacology, State University of New York, Upstate Medical Center, Syracuse, New York 13210.© 1984 by The University of Chicago. AU rights reserved. 0031-5982/84/2703-0393$01.00 Perspectives in Biology andMedicine, 27,3 · Spring 1984 | 367 also founder on the resistance, as in other historical analyses, to unitary explanations, as well as on the intrusion of such "irrational" factors as fashion, iconoclasm, egotism, and novelty. Closer attention to specific cases may nevertheless afford opportunities for evaluating competing explanations of conflict resolution, revealing how the scientists dealing with a particular problem make actual choices among rival formulations. This account will thus consider the rise of the chemiosmotic hypothesis as a specific case of theory choice made by practicing scientists, a case in which the triumph over rival formulations is interpretable as a choice based prominendy on perceived fruitfulness, on scientific opportunity. Oxidative Phosphorylation and the Chemical-Intermediate Hypothesis Mitchell originally proposed the chemiosmotic hypothesis as an alternative to the established chemical-intermediate hypothesis of energy coupling. Like its rival, Mitchell's hypothesis dealt with the mechanism by which energy is conserved through the synthesis of adenosine triphosphate (ATP), a molecule with high chemical potential energy, from adenosine diphosphate and inorganic phosphate (ADP and P¿). Mitchell's hypothesis accounted for ATP synthesis driven both by light energy, photophosphorylation, and by oxidation ofcellular metabolites, oxidative phosphorylation; for brevity, this account will concentrate chiefly on oxidative phosphorylation catalyzed by cellular mitochondria and will begin with a brief review of pertinent mitochondrial processes and of the older hypothesis. It should, however, be emphasized that a salient although not unique feature of the chemiosmotic theory was its encompassing within a single framework photophosphorylation by plant chloroplasts as well as oxidative phosphorylation by mitochondria and bacteria; in addition, some of the outstanding experimental projects relevant to the theory deal with systems other than mitochondrial. Ernster and Schatz [6] recently summarized the scientific history of mitochondria and Skulachev [7] and Mitchell [8] diat of the chemiosmotic hypothesis. Mitochondria contain the biological machinery for oxidative metabolism , with its consumption of O2, production of CO2, and formation of ATP. This cellular respiration involves oxidation of metabolic fuels by dehydrogenation, with the concomitant reduction of mitochondrial coenzymes. The oxidation-reduction (redox) process in essence involves the transfer of two hydrogen atoms to the coenzyme, chiefly to nicotinamide adenine dinucleotide (NAD+), forming the reduced coenzyme , (NADH) and H+. The NADH is subsequently reoxidized to NAD+, two hydrogen atoms ultimately being transferred to one oxygen atom to form water, H2O. This transfer of hydrogen atoms...