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Life at the Cell and Below-Cell Level: The Hidden History of a Fundamental Revolution in Biology (review)
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Perspectives in Biology and Medicine 45.4 (2002) 628-631

Book Review

Life at the Cell and Below-Cell Level:
The Hidden History of a Fundamental Revolution in Biology

Life at the Cell and Below-Cell Level: The Hidden History of a Fundamental Revolution in Biology. By Gilbert N. Ling. New York: Pacific Press, 2001. Pp. 373. $19.95.

This book outlines the history of scientific efforts to describe the organization and functions of living cells in physicochemical terms. There is not a single path towards more knowledge and understanding of biological materials; rather, two opposing scientific schools have evolved. As the subtitle of the book suggests, a revolutionary hypothesis of cell structure and function has been developed that is almost unknown or hidden to contemporary scientists.

Ling explains the experiments and theoretical modeling that led to the membrane pump theory, nowadays taught in all textbooks as fact and serving as the foundation for much biological and biomedical research. This theory accounts for the four major physiological manifestations of living cells—solute distribution, solute permeability, volume regulation, and electrical potentials—in terms of a steady-state model with the following features. A cell membrane separates the interior of a living cell from the extracellular solution. The bulk of intracellular water—the main component of the cell—is normal free water in which the main cellular cation, K+, and many other solutes are freely dissolved. Energy-consuming pumps in the cell membrane (and in membranes of subcellular compartments) regulate the chemical composition of the cell. In particular, the asymmetric distribution of Na+ and K+ between the outside (low K+, high Na+) and inside (high K+, low Na+) of the cell is maintained by the continuous operation of the Na/K ATPase—an ion pump in the plasma membrane. "High energy" that is stored in ATP molecules is liberated during their hydrolytic splitting and used to fuel the pumps and to perform physiological work.

Largely forgotten or hidden from this account are the experimental findings and theoretical considerations supporting equilibrium models of cell function. According to the so-called bulk-phase theories, the entire cell substance, or protoplasm, has unusual life-specific colloidal properties. Ling discusses early bulk-phase theories and the reasons for their rejection by the scientific establishment in the middle of the last century, and then describes the development of a new bulk-phase theory, the association-induction hypothesis (AIH). Statistical mechanics provided the broad conceptual framework for this theory. The main reason for rejecting the membrane pump theory and for constructing a new model is given in Chapter 12: experimental findings led to the conclusion that under well-defined conditions the postulated ion pump does not command enough energy and is therefore not tenable from a thermodynamic point of view.

The AIH describes the resting living state as a metastable equilibrium, in which water, proteins, and ions are at equilibrium in an associated state. Both the cell surface (membrane) region and the cytoplasm are highly organized protein-ion-water systems. Membrane-situated Na/K pumps do not exist. (Active ion transport across epithelia or frog skin is not disputed; it is explained in terms of the AIH.) Most cellular K+ ions are adsorbed on anionic protein side chains, and intracellular water is adsorbed in polarized multilayers on polypeptide chains; thus, cellular constituents exist in a dynamically ordered and functionally coherent array. The interactions between proteins, ions, and water are weak interactions that allow rapid adsorption and desorption. The cellular Na+ concentration is low because the highly hydrated Na+ ion has a reduced solubility in the organized cellular water and because the anionic protein side chains prefer K+ to Na+ . Interactions between cellular components is made possible by proteins, in which long-range information and energy transfer is achieved by repetitions of short-range propagation of electrical polarization and depolarization, or induction. Based on these concepts, Ling derives theoretical equations that describe solute distribution, solute permeability, volume regulation (mainly determined by the hydration of cellular proteins), and electrical potentials (explained as "close-contact" surface adsorption potentials) in a unifying manner. In addition, he proposes a molecular-electronic theory of how drugs control cell function. According to the AIH, work...

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