Is "Life" Based on Clockwork Biology or Quantum Uncertainty?

IS "LIFE" BASED ON CLOCKWORK BIOLOGY OR QUANTUM UNCERTAINTY? M. B. HALLETT* Introduction Life, whether ofsingle-celled or multi-cellular organisms, is characterized by an inherent uncertainty in the responses ofindividual cells to stimuli [I]. This intrinsic unpredictability of response of individual cells, while often overlooked, is a key element in cell biology. Probability and stochastic behavior are key concepts in a number of cellular phenomena, from cell Chemotaxis to quantal neuro-secretion, and subcellular phenomena from ion channel opening and more recently the generation of Ca2+ puffs and sparks [2-5]. The probabilistic nature of cell behavior must, therefore, be taken into account in any full description of the workings of the cell. The unpredictability arises because the small size of cells and organelles limits the number of molecules within them to the point where mass action "predictions" do not apply and the stochastic behavior of the microworld of molecules becomes apparent [I]. The role of probability, resulting from molecular chaotic behavior in "life," was probably first considered in the 1930s and 1940s, when widely argued about and discussed by eminent scientists such as Gray, J. S. Haldane, and Schrödinger [6-8]. Gray went as far as suggesting that "The means whereby chance . . . [is] . . . used for carrying out essential life processes . . . [is] ... in effect the secret of life" [6]. The predictability of diffusion rates, binding rates, and chemical reactions rates arises because millions, if not millions of millions, of individual independently behaving particles have an extremely low probability of all "misbehaving" together. The number of key signalling molecules within cells may be a long way away from this situation. The number of receptors and ion channels on the membrane of many cells, for example, may be only of the order of a few hundred to a thousand [9, 10]. The random *Molecular Signaling Group, University Department of Surgery, University of Wales, College of Medicine, Heath Park, Cardiff, CF4 4XN, United Kingdom.© 1997 by The University of Chicago. All rights reserved. 0031-5982/97/4004-1024$01.00 Perspectives in Biology and Medicine, 41, 1 ¦ Autumn 1997 101 micro-behavior of these small number of molecules results in the unpredictability of cellular behavior when fluctuations in the concentrations or stochastic behavior of micro-events are coupled to all-or-none, irreversible macro-events within the individual cell [I]. Far from being a trivial consequence of the small size of the cell, this effect lies at the heart of the biological behavior of individual cells, and hence the behavior of tissues and organisms [I]. The unpredictability and unreliability of behavior of individual cells provided the evolutionary pressure for the formation of multicellular organisms. In tissues and organisms, individual cells cooperate with each other, either by physical coupling with gap junctions or by signalling by extracellular messengers. In either case, the shared behavior of groups of cells in tissues and organisms would minimize the uncertainty of individual cell behavior and produce more predictable and hence reliable behavior. Thus cellular unpredictability may be a key for explaining a number of biological phenomena. The Source of Biological Unpredictability In the foregoing brief description (and more fully in a previous essay [I]), the source of the cellular unpredictability was ascribed to the molecular unpredictability of small numbers of particles. The question as to the source of the molecular unpredictability must therefore be answered. Without complete knowledge of all the positions and velocities of all the particles in the universe, the future position of an individual molecule or ion within a particular cell cannot be known. Probability and randomness are, therefore, the only feasible descriptions of the behavior of small numbers of molecules. For example, a mathematical description of the diffusion of an agent from a high to low concentration region can be accurately made by starting with the assumption that the individual molecules move randomly. This could occur as a result of "billiard-ball" type collisions between the molecules of interest and other molecules, such as of water, to give rise to random behavior. However, the result of billiard-ball type molecular collisions in which velocities and positions are known, would be predictable and reproducible . Thus, in a thought experiment, in which the diffusion...