J. theor. Biol. (2003) 220, 393–406 doi:10.1006/jtbi.2003.3178, available online at http://www.idealibrary.com on The Driving Force for Life’s Emergence: Kinetic and Thermodynamic Considerations Addy Pross n Department of Chemistry, Ben-Gurion University of the Negev, P.O. Box 643, Beer Sheva 84105, Israel (Received on 26 December 2001, Accepted in revised form on 23 September 2002) The principles that govern the emergence of life from non-life remain a subject of intense debate. The evolutionary paradigm built up over the last 50 years, that argues that the evolutionary driving force is the Second Law of Thermodynamics, continues to be promoted by some, while severely criticized by others. If the thermodynamic drive toward ever- increasing entropy is not what drives the evolutionary process, then what does? In this paper, we analyse this long-standing question by building on Eigen’s ‘‘replication first’’ model for life’s emergence, and propose an alternative theoretical framework for understanding life’s evolutionary driving force. Its essence is that life is a kinetic phenomenon that derives from the kinetic consequences of autocatalysis operating on specific biopolymeric systems, and this is demonstrably true at all stages of life’s evolution F from primal to advanced life forms. Life’s unique characteristics F its complexity, energy-gathering metabolic systems, teleonomic character, as well as its abundance and diversity, derive directly from the proposition that from a chemical perspective the replication reaction is an extreme expression of kinetic control, one in which thermodynamic requirements have evolved to play a supporting, rather than a directing, role. The analysis leads us to propose a new sub-division within chemistry F replicative chemistry. A striking consequence of this kinetic approach is that Darwin’s principle of natural selection: that living things replicate, and therefore evolve, may be phrased more generally: that certain replicating things can evolve, and may therefore become living. This more general formulation appears to provide a simple conceptual link between animate and inanimate matter. r 2003 Elsevier Science Ltd. All rights reserved. Introduction The nature of the driving force that led to the emergence of animate matter remains a subject of continuing debate and uncertainty. What physico-chemical principles led to the emergence of biological complexity, to the formation of increasingly complex far-from-equilibrium sys- tems exhibiting purposeful structure and beha- vior? And given that it is the Second Law of Thermodynamics that governs the direction that all spontaneous processes must necessarily fol- low, how do these principles relate to the Second Law? One reason for much of the confusion that has enveloped this fundamental issue derives from the fault line that continues to separate biology and physics. The ‘‘autonomy of biology’’ approach to science, invoked some 200 years ago by Kant (1952) with his ‘‘natural purpose’’ concept, and reinforced by modern biologists such as Mayr (1988), had the unintended effect of impeding attempts to provide a physical n Tel.: +972-8-646-1193; fax: +972-8-647-2943. E-mail address: pross@bgumail.bgu.ac.il (A. Pross). 0022-5193/03/$35.00 r 2003 Elsevier Science Ltd. All rights reserved.