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Toward a general theory of evolution: ExtendingDarwinian theory to inanimate matterAddy Pross

Abstract

Though Darwinian theory dramatically revolutionized biological understanding, its strictly biological focus hasresulted in a widening conceptual gulf between the biological and physical sciences. In this paper we strive toextend and reformulate Darwinian theory in physicochemical terms so it can accommodate both animate andinanimate systems, thereby helping to bridge this scientific divide. The extended formulation is based on therecently proposed concept of dynamic kinetic stability and data from the newly emerging area of systemschemistry. The analysis leads us to conclude that abiogenesis and evolution, rather than manifesting two discretestages in the emergence of complex life, actually constitute one single physicochemical process. Based on thatproposed unification, the extended theory offers some additional insights into life’s unique characteristics, as wellas added means for addressing the three central questions of biology: what is life, how did it emerge, and howwould one make it?

1. IntroductionDespite the enormous developments in molecular biol-ogy during the past half century, the science of biologyappears to have reached a conceptual impasse. Woese[1] captured both the nature and the magnitude of theproblem with his comment: “Biology today is no morefully understood in principle than physics was a centuryor so ago. In both cases the guiding vision has (or had)reached its end, and in both, a new, deeper, more invi-gorating representation of reality is (or was) called for.”The issue raised by Woese is a fundamental one - tounderstand the genesis and nature of biological organi-zation and to address biology’s holistic, rather than justits molecular nature. Kauffman [2] expressed the diffi-culty in somewhat different terms: “....we know many ofthe parts and many of the processes. But what makes acell alive is still not clear to us. The center is stillmysterious.” In effect, the provocative question, “Whatis Life?”, raised by Schrödinger over half a century ago[3], remains unresolved, a source of unending debate.Thus, despite the recent dramatic insights into themolecular character of living systems, biology of the 21st

century is continuing to struggle with the very essenceof biological reality.

At the heart of biology’s crisis of identity lies itsproblematic relationship with the two sciences that dealwith inanimate matter - physics and chemistry. Whilethe on-going debate regarding the role of reductionistthinking in biology exemplifies the difficulties at a meth-odological level, the problematic relationship manifestsitself beyond issues of methodology and philosophy ofscience. Indeed, the answers to two fundamental ques-tions, central to understanding the life issue, remainfrustratingly out of reach. First, how did life emerge,and, second, how would one go about synthesizing asimple living system? Biology cannot avoid these ques-tions because, together with the ‘what is life?’ question,they form the three apexes of the triangle of holisticunderstanding. Being able to adequately answer any oneof the questions depends on being able to answer theother two. A coherent strategy for the synthesis of aliving system is not possible if one does not know whatlife is, and one cannot know what life is if one does notunderstand the principles governing its emergence.Richard Feynman’s aphorism (quoted in [4]) capturedthe issue succinctly: “What I cannot create, I do notunderstand”. Remarkably, the laws of physics and chem-istry, the two sciences that deal with material structureand reactivity, have as yet been unable to adequatelybridge between the physicochemical and biologicalworlds.

Correspondence: [email protected] of Chemistry, Ben Gurion University of the Negev, Be’er Sheva,84105, Israel

Pross Journal of Systems Chemistry 2011, 2:1http://www.jsystchem.com/content/2/1/1

© 2011 Pross; licensee Chemistry Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

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Despite the above-mentioned difficulties we believethat the problem is resolvable, at least in principle. Ifthe widely held view that life did emerge from inanimatematter is correct, it suggests that the integration ofanimate and inanimate matter within a single concep-tual framework is an achievable goal. This is trueregardless of our knowledge of the detailed historicalpath that led from inanimate to animate. The very exis-tence of such a pathway would be proof for that. Ifindeed such a conversion did take place, it suggests thatparticular laws of physics and chemistry, whethercurrently known or not, must have facilitated that trans-formation, and therefore those laws, together with thematerials on which they operated, can form the basis forunderstanding the relationship between these twofundamentally distinct material forms.In this paper we wish to build on this way of thinking

and to draw the outlines of a general theory of evolution,a theory that remains firmly rooted in the Darwinianlandscape, but reformulated in physicochemical termsso as to encompass both biological and non-biologicalsystems. Such a theory, first and foremost, rests on abasic assumption: that the physicochemical principlesresponsible for abiogenesis, the so-called chemical phase- the stage in which inanimate matter complexified intoa simple living system - are fundamentally the same asthose responsible for biological evolution, though forthe biological phase these principles are necessarilydressed up in biological garb. Darwin would no doubthave drawn enormous satisfaction from such a proposal,one that attempts to integrate Darwinian-type thinkinginto the physicochemical world. However such a sweep-ing assumption needs to be substantiated. Accordinglyour analysis is divided into two parts. In the first partwe argue for the basis of that assumption, and in secondpart we attempt to describe key elements of that generaltheory, as well as the insights that derive from it, in par-ticular with regard to the three central questions of biol-ogy, referred to above. The analysis draws heavily ondata from the emergent research area termed by Güntervon Kiedrowski, ‘Systems Chemistry’ [5,6]. The essenceof this emergent area is to fill the chemical void betweenchemistry and biology by seeking the chemical origins ofbiological organization.

2. Discussion2.1. Unification of abiogenesis and evolutionDarwinian theory lies at the very heart of modern biol-ogy, and rightly so. As Dobzhansky [7] famously noted:“Nothing in biology makes sense except in the light ofevolution”. Yet despite the extraordinary and over-whelming impact of Darwin’s ideas on biology andbeyond, Darwinian theory does not address the Originof Life problem, even though the nature and source of

early life could well impact on the theory itself. Interest-ingly, this limitation was already obvious to Darwin’scontemporaries. Thus just three years after the publica-tion of Darwin’s monumental thesis, Haeckel [8,9]pointed out that “the chief defect of the Darwiniantheory is that it throws no light on the origin of the pri-mitive organism–probably a simple cell–from which allthe others have descended. When Darwin assumes aspecial creative act for this first species, he is not con-sistent, and, I think, not quite sincere...”. Surprisingly,this early concern seems to have dissipated with time.Thus a leading biologist, Richard Dawkins, in theopening line of his book ‘The Blind Watchmaker’writes: “... our existence once presented the greatest ofall mysteries, but that it is a mystery no longer becauseit is solved. Darwin and Wallace solved it....” [10]. Yes,Darwinism did resolve the dilemma of how microscopiccomplexity was transformed into macroscopic complex-ity, however it did not resolve or even address the mostvexing of questions: how did the extraordinary micro-scopic complexity of the simplest living system emergein the first place?It is not surprising then that the emergence of com-

plex life on earth is divided into two phases - abiogen-esis, the chemical phase, and evolution, the biologicalphase (as illustrated in 1), with the first phase being theone that remains a source of confusion and continuingcontroversy (for a recent special issue on the origin oflife, see [11], for general reviews, see [12-15]). But whatif these two stages could be conceptually merged intoone single continuous physicochemical process? Suchunification could significantly impact on our under-standing of the life phenomenon, as we would then befaced with the need to understand just one single pro-cess, rather than two separate and discrete processes.And given our broad understanding of the Darwinianphase, that understanding could be immediately appliedto the poorly understood earlier chemical phase. But arethere reasonable grounds for such a sweeping proposal?We believe the answer to be yes, and base this view onrecent developments in systems chemistry. Recent workon molecular replicating systems has revealed that sev-eral phenomena associated with replicating chemicalsystems are also manifest in biological systems. Thisgeneral observation is crucially important because itprovides the empirical basis for the conceptual link

Scheme 1 Two-phase (chemical and biological) transformation ofnon-life into complex life.


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between chemistry and biology, not just at the self-evi-dent structural level (i.e., both animate and inanimatematter are constructed from atomic and molecular enti-ties), but at some deeper organizational level. Indeedthis evidence will form the basis of our proposal thatthe chemical and biological phases are in fact one singleprocess. Let us first review the relevant empirical data.2.1.1. Natural selection at the chemical levelAlready in the 1960s, Mills et al. [16] noted that a mole-cular replicating system, Qb RNA, when reacted withactivated nucleotides in the presence of the appropriatereplicase, underwent a process of replication, mutation,selection, evolution, in striking analogy to biological sys-tems. The RNA oligonucleotide, originally some 4200bases in length, replicated, mutated and evolved into amuch shorter oligonucleotide chain just 17% of theoriginal length, that replicated much faster than the ori-ginal chain [15,16]. This observation, even on its own,suggests that Darwinian behavior, a fundamentally biolo-gical phenomenon, has its roots in chemistry. No onewould seriously argue that a single molecule, whateverits structure, is in any meaningful sense ‘alive’, yetDarwinian-type behavior is strikingly evident at thisinanimate, molecular level [15,16]. Since then in vitroevolution procedures have been developed and extendedto cover a wide range of nucleic acid systems as demon-strated by the work of Bartel and Szostak [17], Johnstonet al. [18] and Joyce et al. [19,20], thereby emphasizingthe generality of evolutionary-like processes at the mole-cular level.An even more striking expression of natural selection

at the chemical level that further highlights the extentof the chemistry-biology nexus has recently beenreported by Voytek and Joyce [21]. A key ecologicalprinciple, the competitive exclusion principle [22]states: “Complete competitors cannot coexist”, or in itsmore positive expression: “Ecological differentiation isthe necessary condition for coexistence”. That principleinforms us that two non-interbreeding populations thatoccupy precisely the same ecological niche (i.e., bothcompeting for the same resource) cannot coexist - onewill drive the other into extinction. The striking aspectof Voytek and Joyce’s study was that it demonstratedthat the roots of this quintessential biological principlecan be found in chemistry. They reported that twoRNA enzymes, when allowed to replicate and evolve inthe presence of an essential substrate, were unable tocoexist. One of the enzymes drove the other intoextinction in line with the prediction of the competi-tive exclusion principle. More significantly, however,when the two enzymes were simultaneously reactedwith five alternative substrates, the two enzymes wereable to coexist. Each RNA enzyme evolved so as tooptimize its utilization of one of the 5 substrates (a

different substrate for each of the two enzymes) sothat the system effectively mimicked biological nichebehavior, again in accord with the exclusion principle.Darwin ’s classic finches niche behavior [23] at thechemical level!As noted above, both chemical and biological

replicators respond in a strikingly similar way to thereplication-mutation-selection-evolution causal chain.But there is an additional consequence of that causalchain that manifests itself at both the chemical and thebiological levels - the process of complexification. Let usexplain.2.1.2. Complexification at both chemicaland biological levelsWithin the biological world there is no doubting that adefinite process of complexification over the extendedevolutionary time frame has taken place. Though thedetailed path toward cellular complexity remains contro-versial, the existence of that evolutionary drive towardgreater complexity cannot be denied. Thus it is conven-tional wisdom to believe that the more complex eukar-yotic cell evolved from simpler prokaryotic cellularorganization, most likely following some endosymbioticevent [24], and in a more recent evolutionary saltation,that multi-cellular organisms evolved from single cellones. The evolutionary dynamic appears to be driven, atleast in part, by the biological advantages associatedwith complexification.Given the unambiguous evidence for complexification

during biological evolution, it is of cardinal interest toobserve whether that same complexification tendencycan be discerned at the chemical level, i.e., withinrelatively simple chemical replicating systems. In view ofthe relatively brief period of time such systems havebeen studied the amount of data remains limited. None-theless some preliminary conclusions may be tentativelyoffered. The idea of a hypercyclic cooperative networkat the molecular level was first proposed by Eigen andSchuster [25], but it was only in 1994 that replicationbased on the cross-catalysis of two oligonucleotides wasreported by Sievers and von Kiedrowski [26]. Subse-quently other functional groups were also shown toexhibit autocatalytic behavior through the establishmentof cooperative cross-catalytic networks. Thus Lee et al.[27] and Yao et al. [28] demonstrated network forma-tion in self-replicating peptides and, more recently,Kindermann et al. [29] and Kassianidis and Philp [30] haveobserved cross-catalysis in a self-replicating Diels Alderreaction, suggesting that cooperative molecular behaviorwithin a replicative context may be quite general.A more explicit demonstration of the replicating

advantages associated with a network as opposed to anindividual molecular replicator, however, was recentlydemonstrated by Lincoln and Joyce [31]. Whereas a


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particular RNA autocatalyst was incapable of more thantwo successive doublings, each of which took about 17h to occur, conversion of that RNA ribozyme into across-catalytic network based on two RNA ribozymesresulted in the formation of a rapidly replicating systemwith a doubling time of just 1 h, which could be sus-tained indefinitely. Thus a cooperative cross-catalyticsystem derived from an autocatalytic parent through anevolutionary process, proved to be a more effectivereplicator ("fitter” in biological jargon), than the autoca-talytic parent precursor. The above results, though stilllimited in scope, suggests that cooperative behavior canemerge and manifest itself at the molecular level, thatthe drive toward more complex replicating systemsappears to underlie chemical, and not just biological,replicators. The implications of these preliminary find-ings appear to be far-reaching. They suggest that thebiological drive toward greater complexity has its rootsin chemistry, that the entire evolutionary process can betraced back to kinetic forces at the molecular level!2.1.3. Significance of common patterns at chemicaland biological levelsThe observation of the same complexification tendencyin both chemical and biological phases is significant inyet another sense. Complexification is not just a phe-nomenon associated with the two phases, it can also beviewed as the mechanism by which the chemical phaseeventually merges with (and into) the biological phase!Ultimately the primary distinction between the chemicaland biological phases appears to be in the degree of com-plexification that has come about, rather than in thenature of the process itself. Clearly then, the trendtoward greater complexity that is manifest at the chemi-cal level could be expected to lead over the extendedevolutionary time scale to the enhanced complexity thatis evident at the biological level. Thus complexification,primarily through network establishment that maintainsthe system’s holistic replicative capability, is the meansby which the simple replicating systems of chemistry aretransformed over time into the highly complex replicat-ing systems that we term biology. The implication isclear: life’s emergence began with the chance appearanceof some relatively simple replicating chemical system,which then began the long road toward increasinglycomplex replicating entities.

2.2. Toward a general theory of evolution2.2.1. Uncovering the chemical roots of DarwinismWe have already pointed out that the Darwinian-typethinking has been applied to molecular replicators,thereby extending its reach to the chemical domain.However a methodological difficulty arises with thisapproach. Consider, Darwinian theory was proposed onthe basis of data, terminology, and concepts that are all

biological. Darwinian theory is therefore, by definition, abiological theory. Indeed, being a biological theory, Dar-win himself considered the possibility of an earlier che-mical phase preceding the biological phase as one thatcould not be adequately addressed within that biologicalframework. In a now famous letter to Joseph DaltonHooker written in March 1863, Darwin wrote: “...it ismere rubbish thinking at present of origin of life; onemight as well think of origin of matter” [9]. Accordingly,if the chemical and biological phases constitute a singlephysicochemical process as we have suggested, then itlogically follows that Darwinian theory needs to beextended and reformulated so that it can also encom-pass inanimate chemical systems. Note that it is not suf-ficient to simply conclude that Darwinian concepts areapplicable to chemical systems as well as biologicalones. While not denying the didactic value of suchthinking, the application of biological concepts to che-mical phenomena is, in a scientific methodologicalsense, problematic, even flawed. Deeper insights into thebiological-chemical connection can be provided, butonly when the connection is approached in the reversedirection. Let us elaborate on this key idea.Scientific reductionism, a central scientific methodol-

ogy, teaches us to seek understanding within higherhierarchical level sciences by using concepts from lowerhierarchical level sciences, not the other way around.That suggests we should seek to explain biological phe-nomena in chemical terms, not chemical phenomena inbiological terms. To clarify the point with an extremeexample, consider the two sciences, chemistry and psy-chology. While a proposed molecular explanation forsome psychological phenomenon might be intriguing andarouse interest, a psychological explanation for somemolecular phenomenon would only be met with derision!To quote Weinberg [32]: “Explanatory arrows alwayspoint downward”. Thus we routinely attempt to explainpsychological phenomena in biological terms, biologicalphenomena in physical and chemical terms, chemicalphenomena in physical terms, and so on, not the otherway around. The observation of Darwinian-like behaviorat the chemical level is highly significant, not because itsuggests that molecules behave in a biological fashion,but because it opens up the possibility of explainingbiological behavior in chemical terms. It enables thechemical roots of that most central and profoundbiological theory, Darwinian theory, to be laid bare,thereby providing a truly fundamental basis for the bio-logical - chemical connection.2.2.2. Chemical kinetics as the basis for Darwinian behaviorAs mentioned above, the temptation to interpret thebehavior of molecular replicators in biological terms -fitness, natural selection, survival of the fittest, etc.,should be firmly resisted. Chemical phenomena are


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more usefully explained in chemical terms, and thecompetitive reactions of molecular replicators are readilyaddressed by the specific branch of chemistry that dealswith the rates of chemical reactions - chemical kinetics.As has been appreciated since the early pioneering workof Lotka [33], the replication reaction, exemplifying anautocatalytic process, is kinetically unique in that unmi-tigated replication will often result in exponentialgrowth. However, exponential growth is inherentlyunsustainable, so, at best, a replicator steady state wouldbe formed in which a balance between the rates ofreplicator formation and replicator decay is established.This kinetic pattern can be expressed by a differentialkinetic equation, such as eq 1, where X is the replicatorconcentration, M is the concentration of building blocksfrom which X is composed, and k and g are rate con-stants for replicator formation and decay, respectively. Asteady state population, a state that is effectively ‘stable’,is achieved and maintained as long as dX/dt remainsclose to zero. A direct consequence of this steady statedescription is that the stability of the resulting state is ofa dynamic kind - the population of replicators is stableeven though the individual members are being continu-ally turned over.

dX/dt = kMX− gX (1)

Significantly, the very existence of such dynamic stateshas profound chemical consequences since, as we havenoted in previous work, a distinct kind of chemistrywith different selection rules arises [34-36]. An exampleof that selection rule pointed out some years ago byLifson [37] is the competitive reaction of two replicatorscompeting for the same building blocks. The likelyresult - one of the replicators will be eliminated. Thus,at the chemical level, the competing reaction of tworeplicating molecules, where one of the replicators is ‘dri-ven into extinction’, is a straightforward andwell-understood chemical kinetic phenomenon. Giventhat chemistry is the more fundamental science, one cantherefore say that biological natural selection emulateschemical kinetic selection, i.e., biology reduces to chemistryfor this most fundamental of biological phenomena [36].The process of complexification, the second pattern

observed in both biological and chemical evolution, canalso be understood as a kinetic phenomenon. It is at thechemical level, where the transformation of a simplemolecular replicator to a autocatalytic network of mini-mal complexity can be examined directly [26-30], thatthe kinetic advantage of the network over the singlereplicator appears to manifest itself. More experimentaldata are needed to fully establish the connectionbetween kinetic selection and complexification, but thepreliminary evidence, particularly that provided by

Lincoln and Joyce [31], is highly suggestive. Thus kineticselection, an inherently chemical phenomenon, one thatis well-established at the molecular level, is increasinglyseen to be at the root of Darwinian-type behavior,thereby providing a basis for a more fundamentalunderstanding of Darwinian behavior at the morecomplex biological level.We have identified biological ‘natural selection’ as an

extension of chemical ‘kinetic selection’, but what is thechemical analogue of ‘fitness’, that other central Darwi-nian concept? What physicochemical property, if any, isbeing optimized by that process of chemical selection?Just where in physicochemical terms is kinetic selectionleading the replicating system? In chemical processes asystem is invariably driven toward a state of greaterthermodynamic stability, but living systems do not seemto follow that directive as all living systems areinherently thermodynamically unstable. It turns out thatthe answer does lie in the system’s stability, but not itsthermodynamic stability, the one we normally address inchemistry. Within the replicating world there is anotherkind of stability, one quite distinct to thermodynamicstability, a stability kind we have termed dynamic kineticstability (DKS) [38,39]. Let us briefly comment on thenature of DKS and discuss how the two kinds ofstability inter-relate.2.2.3. Dynamic kinetic stability (DKS) and dynamickinetic states of matterA system is considered stable if it is persistent, remainsunchanged with time - that is an operational, phenom-enological definition. Within chemical systems werecognize that a system’s stability can arise for eitherthermodynamic or kinetic reasons and, accordingly, wespeak of thermodynamic and kinetic stabilities. Impor-tantly, both arise from lack of change. Paradoxically,however, there is another kind of stability in nature thatis actually achieved through change, rather than throughlack of change. This stability kind is a dynamic stability.Consider, as an example, a flowing river or a waterfountain. The river or fountain, as an identifiable entity,would be classified as stable if it maintains its presenceover time. That, as already mentioned, is the manifesta-tion of stability - unchanging with time. But, of course,the water that makes up the river or fountain is chan-ging constantly so the river’s (fountain’s) stability in thisinstance is of a dynamic kind, one that comes aboutthrough change. So though the river (fountain) as anentity is stable, its stability is of a distinctly differentcharacter to that associated with static entities.As already discussed above, a stable population of

replicating entities, whether chemical or biological, alsomanifests a dynamic kind of stability. The population ofreplicators can only be ‘stable’ if the individual entities


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that make up the population are continually beingturned over, just like the constantly changing water con-tent of the river or fountain. Thus one might think ofthe population of molecular replicators as a ’molecularfountain’. The significance of the term ‘dynamic kineticstability’, as applied to a stable population of replicatingentities, may now become clear. The term ‘dynamic’reflects the continual turnover of the population mem-bers, the term ‘kinetic’ reflects the fact that the stabilityof the replicating system is based on kinetic parameters,such as k and g of eq 1, i.e., on reaction rate constants,rather than on thermodynamic parameters. It is thevalues of these parameters, together with the availabilityof resources, which determines the stability of the parti-cular replicating system. Accordingly we may character-ize stable replicating systems (i.e., those that persist overtime), whether chemical or biological, as dynamic kineticstates of matter. The utility and significance of this termcan be more clearly gauged by comparison with theterm frequently used to describe inanimate systems, themore traditional thermodynamic states of matter thatcharacterize much of chemistry.2.2.4. The physicochemical driving force within replicatorspaceLet us now specify the factors that would tend toenhance the stability of a replicating system. Fundamen-tally all physicochemical systems tend to undergo trans-formations from less stable forms to more stable forms.The second law of thermodynamics is the formal expres-sion of that general drive. But within the constraints ofthe second law a range of outcomes is possible, and forreasons described above, for replicating systems, kineticfactors predominate. Specifically, within replicator space,the space in which dynamic kinetic stability is effectivelyin control, the selection rule becomes: from kineticallyless stable to kinetically more stable. Thus, within thatspace the driving force is effectively the drive towardgreater DKS. In other words, whereas the second lawrequires all chemical systems to be directed toward theirmost stable state (lowest Gibbs energy state), withinreplicator space a second law analogue effectively governsthe nature of transformations [36,39]. A recent study byBoiteau and Pascal [40] also reaffirms the idea of a funda-mental evolutionary driving force.The above discussion now makes clear a major distinc-

tion between events within the physical and biologicalworlds. Within the physical world the second law is auseful predictor of what is likely to take place. That ishow we are able to predict the melting of ice when placedin warm water, or the explosion that results from themixing of hydrogen and oxygen gases. Generally speak-ing, that is the law that allows us to relate reactants andproducts for any reaction in an intelligible fashion.Within the biological world, however, that world of

replicating systems, the second law provides effectivelyno predictive power. Neither the behavior of a stalkinglion nor the single cell phenomenon of chemotaxis isexplicable in terms of the second law. Of course all biolo-gical phenomena are consistent with the second law, butthat global requirement in itself is of no predictive value.Rather, biological phenomena can be best understoodand predicted on the basis of their teleonomic character[41,42], a character that is totally unrelated to thermody-namic stability and the second law. The behavior of ahungry lion or of a bacterium in a glucose solution with aconcentration gradient are each readily understood andpredicted in teleonomic, not thermodynamic, terms. Aswe will discuss shortly, teleonomy, that quintessentiallybiological phenomenon, can be given a physicochemicalbasis, but it will be by relating it to kinetic, as opposed tothermodynamic, parameters.2.2.5. Quantification of dynamic kinetic stabilityHaving established the existence of a discrete kind of sta-bility that differs from the previously recognized stabilitykinds, it would be clearly beneficial to be able to quantifythe concept. Unfortunately there is inherent difficulty inthe formal quantification of DKS and this difficulty mani-fests at several levels. First, one cannot formally comparethe DKS of any two arbitrary replicators, say, a bacteriumand a camel, because these two entities are not directlyrelated. In this regard the issue is not too different tothermodynamic stabilities, where one cannot formallycompare the stabilities of two systems that are not iso-meric. Thus, just as one cannot legitimately ask whethera molecule of water is more or less stable than a moleculeof benzene, one cannot compare the relative stabilities oftwo replicating entities if they do not compete directlyfor the same material resources. Accordingly, the relativeDKS of two arbitrary replicators will, in most cases, notbe formally measureable.Second, if two replicators do compete directly, as in the

case of RNA oligomers competing for the same nucleotidebuilding blocks, then the relative dynamic kinetic stabili-ties can be ascertained, and even quantified, based on therelative rates of replication and decay for the competingreplicators. However, since DKS derives from kineticrather than thermodynamic factors it is likely to be signifi-cantly influenced by minor variations in reaction condi-tions, so the significance of any particular measure wouldbe of limited value. For example, the presence of ethidiumbromide in the reaction mixture during competing RNAoligomer replication leads to a quite different competitiveoutcome than in its absence [43]. Accordingly, the actualmagnitude of DKS for any replicating system, like its staticcounterpart, is highly circumstantial, and therefore is notreadily amenable to meaningful quantification. In fact thedifficulty in quantifying DKS is clearly reflected inattempts over many years to quantify the biological


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equivalent of DKS - ‘fitness’, one that began with Fisher’suse of the Malthusian parameter [44]. Since that early pro-posal, different fitness kinds have been suggested - relativefitness, inclusive fitness, individual fitness, population fit-ness, and different empirical measures of that parameterhave been offered, reflecting the intrinsic difficulty inquantifying the fitness concept [45,46]. All these differentquantification proposals may in a sense be viewed asattempts to square the circle. Indeed, having reduced thebiological concept of ‘fitness’ to the chemical concept ofDKS, helps clarify the source of the difficulty by stressingthe kinetic, and hence circumstantial nature of stabilitywithin a replicative context.2.2.6. Toward a general (extended) theory of evolutionOnce we have satisfied ourselves that the chemical andbiological phases of life’s emergence and evolution canbe unified within a single physicochemical description,one that rests on an identifiable physicochemical drivingforce, the central elements of a general theory of evolu-tion can be outlined. We begin by pointing out that theterminology employed in that formulation is necessarilyphysicochemical so it can address the initial phase oflife’s emergence, the so-called chemical phase. It followstherefore that the biological phase will also be describedin physicochemical terms, but that poses no methodolo-gical difficulty - a reductionist methodology underpinsmuch of the scientific endeavor. Accordingly the follow-ing statement will serve as the central element of thegeneral theory:

■ Certain oligomeric replicating systems, through aprocess of imperfect replication and on-going kineticselection, will tend to evolve toward replicatingsystems of greater DKS.

While initially that process of imperfect replicationmight involve the preferential formation of the more rapidreplicating oligomeric sequences, as demonstrated in theclassic RNA replication experiments of Mills et al. [16],the emergence of replicating networks (also termed auto-catalytic sets) [2,6,47,48] with their enhanced replicatingcapability in comparison with individual molecular replica-tors, would open up new kinetic options within replicatorspace. And those particular sequences that would be cap-able of catalyzing the formation of other chemical classes,e.g., peptides, that exhibit catalytic activity with respect tothe replication reaction itself, would further add to theprocess of complexification and evolution toward morestable dynamic kinetic systems. So while the process ofkinetic selection between competing replicating systemscan show a range of kinetic characteristics, depending onthe precise replication mechanism and its particularkinetic parameters, the general trend from less complexand kinetically less stable to more complex and kinetically

more stable replicators would manifest itself. Accordinglythe second element of the general theory that addressesthe process of complexification may be formulated as fol-lows:

■ Complexification within replicator space, throughthe establishment of increasingly complex chemicalnetworks, will be the primary mechanism for theenhancement of replicator dynamic kinetic stabilityand the generation of stable dynamic kinetic states.

From the above discussion it becomes apparent thatcentral Darwinian (biological) terms are just specialcases of more general physicochemical terms, as indi-cated in Table 1. Biology, through a reductionist per-spective, can be seen to merge smoothly into chemistry.2.2.7. Relationship between dynamic kinetic stability andthermodynamic stability - origin and role of metabolismNotwithstanding the above discussion and its emphasison DKS, the relationship between that stability and ther-modynamic stability needs to be clarified. After all, ther-modynamic requirements, as articulated by the secondlaw, cannot be ignored in that all transformations in thephysicochemical world, regardless of whether the parti-cular system is biological or not, must conform to itsstrict demands. It turns out that metabolism (in theenergy-gathering sense) is the means by which Naturecan have its cake and eat it. Incorporation of an energygathering capability into the system is what enables thedrive toward greater DKS to comfortably coexist withthe strict requirements of the second law, despite theoften opposing requirements of these two stability kinds.Let us consider this point in more detail.Metabolism is broadly defined as the complex set of

reactions that takes place in the living cell. So in thatsense metabolism is the direct manifestation of the ten-dency toward increasing complexification that lies at theheart of the evolutionary process. However, as notedabove, all chemical reactions are bound by the secondlaw so the drive toward greater DKS and the greatercomplexity that frequently accompanies that stabilitymust be consistent with the thermodynamic directive.This is true even though not all paths that seek toenhance DKS will be thermodynamically feasible.Indeed, one can presume that in many cases the greatercomplexity associated with enhanced DKS will actually

Table 1 Key Darwinian concepts and their underlyingchemical equivalent

Biological Term Underlying Chemical Term

Natural selection Kinetic selection

Fitness Dynamic kinetic stability

Survival of the fittest Drive toward greater dynamic kinetic stability


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be disfavored thermodynamically, thereby effectivelyblocking such pathways. So how is this apparent conflictbetween two stability kinds resolved? The potential con-flict is resolved through the emergence of a very specialkind of metabolic complexification - the one specificallyassociated with energy gathering. It is this particularkind of metabolic capability that enables DKS and ther-modynamic stability to comfortably coexist. Let us seehow this can come about.In a recent theoretical study [49], we have demonstrated

that a replicating molecule that acquires an energy gather-ing capability through a chance mutation, e.g., through theformation of a photoactive site within the original mole-cule, can be expected, through a process of kinetic selec-tion, to drive the original non-metabolic replicator intoextinction. In other words, the chance emergence of ametabolic capability would lead to the formation of a repli-cator of greater DKS than the original non-metabolicmolecule. Significantly, this result was observed even if themetabolic replicator was postulated as being inherentlyslower in its replicating step. Effectively the incorporationof the metabolic capability ‘frees’ the replicating entityfrom thermodynamic constraints in much the same waythat a car engine ‘frees’ a car from gravitational con-straints. A motorized vehicle is not restricted to merelyrolling downhill, but through the utilization of an externalenergy source (gasoline), can travel uphill as well. In otherwords, just as a motorized vehicle is a more effective vehi-cle for travel, so a metabolic replicator is a more effectivereplicator than a non-metabolic one. The significance ofthe simulation described above is that it demonstrates thata metabolic capability, once acquired through a chancemutation, is likely to become incorporated into the systemthrough a process of kinetic selection. At that point thedrive toward greater DKS is no longer critically con-strained by thermodynamic impediments. As we will sub-sequently discuss this mechanism for metabolic (energy-gathering) emergence has clear implications regarding themechanism for the emergence of life. In fact that step maybe considered the critical one in the transformation of athermodynamic (’downhill’) replicator into a kineticallydriven, teleonomic one - the critical step that could betaken as signifying the beginning of life. Considered in thisway, death is just the reversion from that (sustained)dynamic kinetic state of matter back to the traditionalthermodynamic one.

2.3. Applications of the general theory2.3.1. Explanatory power of the general theorySince the beginning of recorded history, man has beenacutely aware of the fact that living and non-living sys-tems are distinctly different. One key test of a generaltheory that attempts to encompass both animate andinanimate (as opposed to a purely biological theory)

is that it should be able to address these key animate-inanimate differences. Life’s central characteristics thatrequire explanation are the following:(a) Diversity and adaptation(b) Complexity(c) Homochiral character(d) Teleonomic (purposeful) character(e) Dynamic character(f) Far-from-equilibrium stateOf these characteristics, diversity, adaptation and

complexity, seem explicable in Darwinian terms, thougha recent monograph has suggested that evolutionary the-ory does not adequately explain diversity and complexity,and a new probabilistic principle is offered instead [50].With regard to the remaining characteristics there is littleroom for argument - none have a simple Darwinianexplanation. In fact Monod [41] went as far as to claimsome years ago that understanding life’s teleonomic char-acter was “the central problem of biology”, while Woese[1] saw in life’s dynamic character an inexplicable charac-teristic that necessitated the abandoning of a traditionalreductionist approach to the subject and to seek, as heput it, “a new biology for a new century”. Let us brieflyconsider how each of these characteristics may be betterunderstood in the light of the general theory.(a) Dynamic character of living systemsAs Woese [1] makes clear, living things transcend the

machine metaphor: “Machines are not made of partsthat continually turn over, renew. The organism is. ....Organisms are resilient patterns in a turbulent flow -patterns in an energy flow”. Woese clearly recognizedlife’s dynamic nature, but was troubled that a satisfac-tory explanation within the traditional molecular biologyframework was lacking. Let us now show how a descrip-tion of life as a dynamic kinetic state of matter may gosome way toward resolving Woese’s dilemma.A stable population of replicating molecules, as

discussed earlier, is a dynamic state in that the popula-tion is stable even though the individual molecules areconstantly turning over. Of course a dynamic populationof replicating RNA molecules does not constitute life, sohow does the dynamic character that we have describedmanifest itself in a simple life form, say a bacterial cell?For cellular replicators (say, bacteria) the dynamiccharacter manifests itself at two levels, molecular andcellular. At the molecular level cellular proteins, a keycomponent of all cells, are continually degraded andregenerated as part of the cell’s mechanism for proteinregulation [51]. As a consequence most cellular proteinshave half-lives measured in hours, some even inminutes, meaning that cellular protein, a primary consti-tuent of all living cells, is effectively completely turnedover within several days, serving as yet another example ofthe ‘molecular fountain’ in operation. And, of course, at


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the cellular level, continuing turnover also takes place -new cells are generated through cell division, while exist-ing cells are constantly being degraded. Thus the dynamiccharacter of living systems, central to their function andvery existence, becomes clear through a description of lifeas a dynamic kinetic state of matter. Lastly, it is of interestto note that this dynamic character may also underliemulti-cellular function. For example, in the brain a signifi-cant proportion of brain cells are firing at any givenmoment, and consciousness, one of the most remarkableand intriguing manifestation of biological organization,has recently been attributed to highly transient groupingsof neurons that are in a continuing dynamic process ofchange [52]. The message is increasingly clear - thedynamic nature of life’s processes, at whatever level, is cen-tral to every aspect of biological function.(b) Life’s far-from-equilibrium characterThe second law teaches us that systems are driven

toward their lowest Gibbs energy state. Of course forkinetic reasons systems may be trapped in higher energystates for a time (e.g., a hydrogen - oxygen gas mixture),but life’s far-from-equilibrium state is not simply explainedin this manner. Living things continually expend energy tomaintain that far-from-equilibrium state, and ion concen-tration gradients cannot be simply viewed as (static) kine-tically stable states. In past years a feasible approach tothis question was through the implementation of the the-ory of non-equilibrium thermodynamics [53]. That theorywas able to explain how spontaneous order - so-called‘dissipative structures’, can come about through the actionof a perturbation on a system at equilibrium. Howeverthat approach toward biological systems ended up beingincreasingly questioned. The problem was that modelingliving systems as dissipative structures - whirlpools, heatedliquids, and the like - was unable to provide any insightsinto biological structure and function [54]. As was pointedout by Collier some years ago, there is no evidence thatnon-equilibrium thermodynamics applies to biological sys-tems in a non-trivial manner [55]. The introduction of theDKS concept appears to resolve this dilemma. In the repli-cating world the stability that matters is not thermody-namic stability but DKS, of course consistent with therequirements of the second law. Thus living systems arehighly stable entities despite their far-from-equilibriumcharacter, but the stability kind is dynamic kinetic. And, asdiscussed above, the second law constraint is responsiblefor the emergence of metabolism (in the energy-gatheringsense) as a critical component of all living things, enablingthe two stability kinds, DKS and thermodynamic stability,to comfortably coexist.(c) Teleonomic characterLife’s teleonomic character is arguably the most strik-

ing of all of life’s unique characteristics. In contrast tonon-living things all life forms appear to follow an

agenda. As Kauffman [2] put it: “living systems areautonomous agents - they act on their own behalf”. Wehave recently offered a physicochemical explanation forlife’s teleonomic character [42], so the issue will not bediscussed here in detail. Suffice it to say that its centralelement rests on life’s description as a dynamic kineticstate of matter. Once a replicating system has taken ona metabolic (energy gathering) capability by kineticselection (so as to enhance its dynamic kinetic stability),it is effectively ‘freed’ of thermodynamic constraints, andat that point the replicating system will have taken onteleonomic character. Its directive is no longer the ther-modynamic directive, which defines so-called ‘objective’behavior, but rather the drive toward greater DKS,whose manifestation is interpreted and understood byus as teleonomic character.(d) DiversityLife’s diversity is clear and unambiguous. The number

of species inhabiting the earth is estimated to be in themillions, occupying every conceivable ecological niche,from the poles to the equator, from the bottom of thesea to high in the atmosphere. Despite the clear evi-dence for diversity, the Darwinian model has provideddifferent explanations for that diversity, from naturalselection to random drift [50], the latter in line withSpencer’s early concept of the “instability of thehomogeneous” [56], and the topic remains a source ofcontinuing debate [57]. In this context we would like toadd the insights provided by the dynamic kinetic stabi-lity model of living systems.One interesting distinction between the ‘regular’

chemical world and the replicative world lies in the dif-ferent topologies of their respective spaces. As we havediscussed previously [39], in the ‘regular’ chemical worldall chemical systems are directed toward their thermo-dynamic sink so that the topology of that space is inher-ently convergent (as illustrated in 2). In contrast, withinreplicator space the path toward systems of greater

Scheme 2 Schematic representation of topologies fortransformations in ‘regular’ chemical space (convergent) and inreplicator space (divergent).


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dynamic kinetic stability is not well-defined. In principleany replicating system may enhance its DKS in anynumber of different ways so that each system becomes apotential branching point for other kinetically stable sys-tems, though which systems will be able to maintainthat stability over time (i.e., survive), is a separate ques-tion. Accordingly, the topology of replicator space isdivergent and it is this different topology that provides asimple explanation for the enormous (and constantlygrowing) diversity we find in the biological world. ThusDarwin’s principle of divergence, a subject of continueddebate [57] since it was originally proposed by Darwin,receives a simple topological explanation. This pictureof convergent and divergent spaces for the two chemicalworlds also explains how in the world of replicators weare able to go back in time and seek our evolutionaryroots (convergent going back in time), but cannotpredict future evolutionary changes (divergent going for-ward in time), whereas in the ‘regular’ chemical worldwe can often predict the outcome of future chemicalreactions (convergent going forward in time) but areunable specify how those reacting systems came about(divergent going back in time) [39].(e) ComplexityMuch of the difficulty in explaining life’s complexity is

associated with the inherent thermodynamic instabilityassociated with the organized complexity of life. Whywould increasingly complex and unstable systems tendto form? However, once the nature of stability in thereplicator world is clarified through the concept of DKS,the issue of complexity, at least with respect to itsthermodynamic consequences, appears largely resolved.As we have already pointed out, the stability thatmatters in replicator space is not thermodynamic butDKS, and complexity, primarily through cross-catalyticnetwork formation, contributes to that stability kind.We have already remarked on how two RNA enzymeswere able to establish a sustained autocatalytic network,where no single enzyme on its own possessed that repli-cative capability [31].An additional biological example may help to clarify

the point - virus functionality. Think of a virus simplisti-cally as a two-molecule aggregate - protein + nucleicacid. Within a biotic environment viruses are highlystable entities (in the DKS sense) in that they are able tobe successfully replicated in large numbers, and therebymaintain a large population. Note, however, that thehigh kinetic stability arises through the cross-catalyticeffect of the viral components. Each component facili-tates the replication of the other, i.e., the two compo-nents are replicatively coupled. However, in that samebiotic environment neither individual component will,on its own, be replicated, i.e., each individual componentwould manifest zero DKS. It is the system’s complexity,

as expressed by the cross-catalytic relationship betweenthe viral components, which provides the means ofreplication, leading to the system’s high DKS.(f) Homochiral characterThe stability of chiral systems in ‘regular’ and replica-

tor space is strikingly different. In ‘regular’ chemicalspace a racemic mixture is inherently the more stableone; chiral excess is thermodynamically unstable, andwith time all homochiral systems will tend to becometransformed into the more stable racemic form (if aggre-gation effects are ignored). Within the replicative world,however, where kinetic factors dominate, the reversepattern is observed. Stereochemical recognition iscrucial in biological processes, particularly in the processof replication, so that in a replicative context, homochir-ality, which facilitates such recognition, is the preferredstereochemical outcome. In other words, due to theimportance of stereochemical recognition, homochiralsystems exhibit greater DKS than racemic ones. Thusthe tendency of ‘regular’ chemical systems toward race-mization, and replicating systems toward homochirality,becomes understandable in terms of the stability typeswithin the two chemical spaces. As a final comment it isworth noting that the importance of autocatalysis is notjust manifest in maintaining that homochiral dynamickinetic state, but also in generating it. The symmetrybreaking Soai reaction [58,59] in which a chiral productcan be formed in almost 100% enantiomeric excessfrom an achiral substrate, is explicable in identicalterms. Thus both the generation and the maintenanceof persistent autocatalytic systems derive from the pre-dominant influence of kinetic factors in governing thoseprocesses.2.3.2. Defining LifeThe only uncontroversial statement one might makeregarding attempts to define life is to say the issue ishighly problematic [60,61]. Yet a working definition isimportant and forms the basis for the on-going attemptsto overcome at least some of the difficulties. As recentlypointed out by Cleland and Chyba [60], one of themajor obstacles to successfully defining life is that weare attempting to define something we don’t fullyunderstand. There are sufficient philosophic and linguis-tic difficulties in defining something we do understand,so the problem is only exacerbated when we attempt todefine an entity whose essence remains in dispute, asource of endless debate.Extending the evolutionary theme to inanimate

systems, thereby helping to bridge the animate-inani-mate gap, leads quite naturally to greater insight intowhat constitutes a living system. That insight, in turn,opens the door to a functional definition that may avoidat least some of the commonly recognized difficultiesassociated with attempts to define life in the past.


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A functional definition that seems to overcome at leastsome of those difficulties is as follows:A self-sustained kinetically stable dynamic reaction

network derived from the replication reaction.Note that a central feature of the above definition is

that it attempts to specify the chemical essence of life,i.e., what life is, rather than what living systems do.Consider by comparison the widely cited NASA defini-tion of life: A self-sustained chemical system capable ofundergoing Darwinian evolution [62]. The fact that theNASA definition suffers from a number of deficiencies,including trivial exceptions (e.g., infertile animals, singlerabbits), has been noted and discussed [60]. But the dif-ficulty with the NASA definition appears to be morefundamental. The NASA definition is anchored in aterm that is itself biological - “capable of undergoingDarwinian evolution”. Ideally a life definition that strivesto place living things within a general material contextshould be detached from its biological context. It shouldnot contain elements that are inherently biological, as tosome degree it is then defined in terms of itself.As a final point we note that the above definition

suggests that other life forms could exist, at least inprinciple. The general definition, here in agreement withthe NASA definition, suggests that life forms not relatedto the protein-nucleic acid format as we know it, wouldbe possible, and would likely exhibit the same phenom-enological manifestations of the established protein-nucleic acid form that surrounds us. A detailed discus-sion of this issue is beyond the scope of this article.2.3.3 Further insights of the general theoryLet us now point out some additional insights providedby the general theory beyond those described above.Two central questions raised in the introduction were:How did life emerge? How would we go about synthe-sizing a living system? What insights into these keyquestions does the above theory offer? Let us firstaddress the question of life’s emergence.The proposed general theory of evolution cannot

address the historical question of life’s emergence frominanimate matter. Historical questions can only beaddressed by uncovering the historic record and, for theearly stages of abiogenesis, no historic record is avail-able, or is likely to become available. Neither the fossilrecord nor phylogenetic analysis can take us back to theearliest stages of life’s emergence. However, uncoveringthe physicochemical principles that would have facili-tated such a transformation should be an achievablegoal. After all, those principles would be independent oftime and place and no less applicable then, as now.Indeed by viewing abiogenesis and biological evolutionas one single continuous physicochemical process, wehave in effect outlined the physicochemical frameworkthat would facilitate such a transformation. In a nutshell

that framework rests on the simple idea that in naturethere is a special stability associated with entities thatcan self-replicate, a stability kind that we have termeddynamic kinetic stability. Thus autocatalysis is at thevery heart of both abiogenesis and evolution. Oncesome relatively simple self-replicating entity would haveemerged, whether a single molecule or a minimal mole-cular network, the drive toward greater DKS would haveinduced that minimal replicating system to further com-plexify. The precise chemical nature of that primal repli-cator and its precise complexification pathway, historicalfacts, are unlikely to be ever known. These are historicevents buried deep in the mists of time, but given thecentrality of the nucleic acid system as the replicatingheart of all living systems, it would seem that either anucleic acid system, or at least one closely related tonucleic acids and evolvable from it, would have beenlikely candidates. Importantly, however, the manner inwhich a thermodynamic replicator, one whose replicat-ing reaction would have been strictly governed by ther-modynamic constraints, was transformed into a far-from-equilibrium energy-gathering teleonomic replicat-ing system, is addressed by the theory. One might go asfar as to say that the step in which a thermodynamic(down-hill) replicator was transformed into a metabolic(energy-gathering) replicator was the critical step, asaltation. That was the step, one might argue, in whicha non-living chemical system began to take on the cen-tral life characteristic - teleonomic character [49],thereby crossing the threshold separating animate frominanimate.How would we go about synthesizing a living system?

We certainly are unable to provide an answer to thisquestion, but the extended theory may provide someuseful pointers, particularly as to what is unlikely towork. First, it is important to recognize that a keydistinction between life and non-life is organizational,the former being a dynamic kinetic state of matter.Thus the living state is induced by the dynamic charac-ter of the biomolecules from which living things areconstructed. A simplistic physical analogy that may cap-ture that dynamic character of life is that of a jugglerjuggling several balls. A state where a man is standingnext to those same balls is identical materially, but dis-tinctly different organizationally. And just as it is easy totransform the juggling state to a non-juggling one(a hefty shove of the juggler is likely to do the trick),but more difficult to go in the other direction, so it iseasy to transform the relatively fragile dynamic statethat is life, to the static thermodynamic state represent-ing death. So a strategy that we predict would not workwould be to simply combine the molecules of life intosome supramolecular aggregate. Such an aggregatewould be thermodynamic in nature, not one that is


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dynamic kinetic. Based on the general model presentedabove, a living system could be synthesized throughaccessing a replicative state with a relatively simplereplicating system. Once that replicative state isaccessed, it could then be modified and built upon, onestep at a time, ensuring the holistic replicative capabilityis maintained at each step. The juggler analogy is onceagain helpful. A juggler wanting to juggle 5 balls mightstart with just 2 balls and then add additional balls, oneat a time - step by step. Simply tossing 5 balls at a mandoes not lead to a juggling state. Of course the abovecomments provide no practical guidance in how toachieve that desired end, and we make no pretense tosuggest otherwise. Nonetheless, a general theory of evo-lution may provide a keener awareness of where the dif-ficulties lie thereby helping to avoid strategies that thetheory would identify as problematic.Finally, in closing this section we briefly mention the

‘metabolism first’ vs. ‘replication first’ controversy, along standing question at the heart of the origin of lifedebate [35,63]. In the absence of historical data thatcan throw light on the question of whether life beganthrough the emergence of some replicating systemwhich then complexified, or with the initial emergenceof an autocatalytic metabolic network, a definitive reso-lution of the question appears unlikely. Nevertheless,having a physicochemical model that provides a basisfor the transformation of inanimate to animate couldprovide useful insights. As the general model describedabove makes clear, the essence of life derives from theunique kinetic characteristics associated with autocata-lysis. That, in turn, suggests that all models for theemergence of life should be analyzed with respect tothat critical element. So did life begin with some primalmetabolic system that was holistically autocatalytic, asproposed by the ‘metabolism first’ school of thought, orwith some self-replicating molecule, as proposed by the‘replication first’ school of thought? Consider, Joyce’swork has recently demonstrated that a single RNAenzyme with its constituent building blocks is a poorreplicator and is unable to bring about sustainablereplication. However, the cooperative cross-catalyticsystem involving two RNA enzymes was able to gener-ate a self-sustained system [31]. This key resultsuggests that both template-directed autocatalysis andnetwork formation may well have been critical elementsin the emergence of life, most likely closely synchro-nized. That being the case, we would argue that the‘replication first’ - ‘metabolism first’ debate, as a funda-mental issue in the Origin of Life debate, may nolonger be of real relevance, and should be replacedwith a bridging ’replication and metabolism together’scenario. Simply put, complexification (of the specialkind found in biology) could not have taken place

without replication, and replication without complexifi-cation had nowhere to go. The idea that the distinctionbetween ‘replication first’ and ‘metabolism first’ schoolsof thought may be largely artificial was recentlyexpressed by Eschenmoser [64].

3. Concluding remarksDarwin’s contribution to modern scientific thought isprofound and irrevocable. It has forever changed man’sview of himself and his place in the universe. Bydemonstrating the interconnectedness of all livingthings, Darwin brought a unity and coherence to biol-ogy that continues to impact on the subject to thisday. But a paradoxical side product of that extraordin-ary contribution with its specific focus on living things,was that it resulted in a distancing between the biolo-gical and the physical sciences, one that continues toafflict the natural sciences. The disturbing result -despite the enormous contribution of the Darwiniantheme, Darwinism remains unable to explain what lifeis, how it emerged, and how living things relate tonon-living ones. The challenge therefore is clear. Thescientific goal - the relentless striving toward the unifi-cation of science - requires that the chasm that dividesand separates the biological from the physical sciencesbe bridged.In this paper we have attempted to demonstrate that

by reformulating and incorporating the Darwiniantheme within a general physicochemical scheme, onethat rests on the concept of dynamic kinetic stability,the animate-inanimate connection can be strength-ened. What the general scheme suggests is that life is,first and foremost, a highly complex dynamic networkof chemical reactions that rests on an autocatalyticfoundation, is driven by the kinetic power of autocata-lysis, and has expanded octopus-like from some primalreplicative system from which the process of complexi-fication toward more complex systems was initiated.Thus life as it is can never be readily classified andcategorized because life is more a process than a thing.In that sense Whitehead’s process philosophy [65] withits emphasis on process over substance seems to havebeen remarkably prescient. Even the identification andclassification of separate individual life forms withinthat ever expanding network seems increasingly pro-blematic. The revelation that the cellular mass that wecharacterize as an individual human being (you, me, orthe girl next door) actually consists of significantlymore bacterial cells than human cells (~1014 comparedto ~1013) [66], all working together in a symbiotic rela-tionship to establish a dynamic kinetically stable sys-tem, is just one striking example of the difficulty. Ashumans we naturally focus on what we identify as thehuman component of that elaborate biological


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network, but that of course is an anthropocentric view,one that has afflicted human thinking for millennia. Adescription closer the truth would seem to be that lifeis a sprawling interconnected dynamic network inwhich some connections are tighter, others looser, buta giant dynamic network nonetheless. And it is life’sdynamic character that explains why identifiable indivi-dual life forms - small segments of that giant network- can be so fragile, so easy to undermine through net-work deconstruction, whereas the goal of creating lifeis such a formidable one.A closing remark concerning life’s complexity. Life is

complex - that is undeniable. But that does not necessa-rily mean that the life principle is complex. In fact wewould argue that the life principle is in some senserelatively simple! Indeed, simple rules can lead to com-plex patterns, as studies in complexity have amplydemonstrated [67,68]. So we would suggest that life,from its simple beginnings as some minimal replicatingsystem, and following a simple rule - the drive towardgreater dynamic kinetic stability within replicator space- is yet another example of that fundamental idea.A final comment: this paper has discussed the con-

cept of dynamic kinetic stability in some detail, andthe question as to which stability kind - dynamickinetic or thermodynamic - is inherently preferred innature, could be asked. There is, of course, no formalanswer to this question. In contrast to thermodynamicstability, dynamic kinetic stability is, as noted earlier,not readily quantifiable. Nevertheless an intriguingobservation can be made. Since the emergence of lifeon earth from some initial replicating entity some 4billion years ago, life has managed to dramaticallydiversify and multiply, having taken root in almostevery conceivable ecological niche. Just the bacterialbiomass on our planet alone has been estimated to besome 2.1014 tons, sufficient to cover the earth’s landsurface to a depth of 1.5 meters [69]. The conclusionseems inescapable - there is a continual transformationof ‘regular’ matter into replicative matter (permitted bythe supply of an almost endless source of energy), sug-gesting that in some fundamental manner replicativematter is the more ‘stable’ form. What implicationsthis continuing transformation might have on cosmol-ogy in general is beyond both our understanding andthe scope of this paper.

AcknowledgementsI am indebted to Prof. Jan Engberts for many valuable suggestions, to Prof.Sijbren Otto for his insightful comments on DKS quantification, and toProfessors Gonen Ashkenasy, Michael Meijler, and Leo Radom for helpfulcomments on an earlier draft of the manuscript.

Received: 17 March 2011 Accepted: 7 June 2011 Published: 7 June 2011

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doi:10.1186/1759-2208-2-1Cite this article as: Pross: Toward a general theory of evolution:Extending Darwinian theory to inanimate matter. Journal of SystemsChemistry 2011 2:1.

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