Reciprocal Linkage between Self-organizing Processes is ... · ited form of evolution, capable of leading to more efﬁcient, more environmentally ﬁtted, and more complex forms

Reciprocal Linkage between Self-organizingProcesses is Sufficient for Self-reproduction andEvolvability

Terrence W. DeaconDepartment of Anthropology and Helen Wills Neuroscience InstituteUniversity of California, Berkeley, CA, [email protected]

AbstractA simple molecular system (“autocell”) is described consistingof the reciprocal linkage between an autocatalytic cycle anda self-assembling encapsulation process where the molecularconstituents for the capsule are products of the autocatalysis.In a molecular environment sufficiently rich in the substrates,capsule growth will also occur with high predictability. Growthto closure will be most probable in the vicinity of the most pro-lific autocatalysis and will thus tend to spontaneously enclosesupportive catalysts within the capsule interior. If subsequentlydisrupted in the presence of new substrates, the released com-ponents will initiate production of additional catalytic and cap-sule components that will spontaneously re-assemble into oneor more autocell replicas, thereby reconstituting and some-times reproducing the original. In a diverse molecular envi-ronment, cycles of disruption and enclosure will cause auto-cells to incidentally encapsulate other molecules as well asreactive substrates. To the extent that any captured moleculecan be incorporated into the autocatalytic process by virtueof structural degeneracy of the catalytic binding sites, the al-tered autocell will incorporate the new type of componentinto subsequent replications. Such altered autocells will beprogenitors of “lineages” with variant characteristics that willdifferentially propagate with respect to the availability of com-monly required substrates. Autocells are susceptible to a lim-ited form of evolution, capable of leading to more efficient,more environmentally fitted, and more complex forms. Thisprovides a simple demonstration of the plausibility of open-ended reproduction and evolvability without self-replicatingtemplate molecules (e.g., nucleic acids) or maintenance ofpersistent nonequilibrium chemistry. This model identifies anintermediate domain between prebiotic and biotic systems andbridges the gap from nonequilibrium thermodynamics to life.

Keywordsartificial life, autocatalysis, nonequilibrium, origins of life,protocell, replicator, self-assembly

January 7, 2006; accepted March 30, 2006136 Biological Theory 1(2) 2006, 136–149. c©2006 Konrad Lorenz Institute for Evolution and Cognition Research

Terrence W. Deacon

Although there are a number of outstanding theoretical prob-lems to be solved with respect to life’s physics and chemistry(such as the determinates of protein folding), most of thesehave to do with massive analytic complexity and do not stemfrom uncertainties regarding fundamental laws or principles.Yet despite advances in the realm of basic theoretical biology,there remains considerable uncertainty about the critical stepsin the transition from the prebiotic to the biotic chemistry ofthe simplest molecular systems potentially able to reproduceand evolve. As a result, we still lack a means to approachthe theoretical issues involved in formulating what Kauffman(2000) has called a “general biology.” The aim of this articleis to propose a simple model molecular system that bridgesthe gap between prebiotic and biotic systems with sufficientsimplicity and precision to offer both empirical testability andtheoretical insights into the transition from physical chemistryto life.

Definitions of life are notoriously eclectic lists empha-sizing different attributes exhibited by known life forms de-scribed at various levels of abstraction(see, e.g., comparisonsin Schopf 2002). Probably, the most abstract characteriza-tion was provided by the philosopher Immanuel Kant whoin 1790 defined an organic body as something in which“every part . . . is there for the sake of the other (recipro-cally as end, and at the same time, means).” He further ar-gued that “an organized being is then not a mere machine,for that has merely moving power, but it possesses in itselfformative power of a self-propagating kind which it commu-nicates to its materials though they have it not of themselves”(Kant 1952/1790). Implicit in Kant’s abstract characterizationis the fact that organisms are organized so that their orga-nization resists dissolution by virtue of self-repair and self-replication. Rasmussen et al. (2004) provide a typical moderncounterpart to Kant’s characterization when they argue that“there is general agreement that a localized molecular assem-blage should be considered alive if it continually regeneratesitself, replicates itself, and is capable of evolving.” However,many authors demand more explicit definitions that fill in de-tails of these component processes with additional specifica-tions. For example, Moreno (1998) defines a living organismas “a type of dissipative chemical structure which builds re-cursively its own molecular structure and internal constraintsand manages the fluxes of energy and matter that keep it func-tioning (by metabolism), thanks to some macromolecular in-formational registers (DNA, RNA) autonomously interpretedwhich are generated in a collective and historical process(evolution).”

Although modern accounts can be far more concrete andexplicit than Kant’s, by virtue of their incorporation of over200 years of biological science, this knowledge can be a sourceof distraction, since certain of these criteria may be character-istic of contemporary forms but not of all possible forms of

organism. Beyond the general synergistic character of organicdynamics, three additional explicit criteria are common to mostmodern accounts of life’s most basic properties:

1. Information. Organisms contain and replicate informa-tion, in the form molecular templates that are copied in repro-duction and transcribed to determine the structure of crucialfunctional components.

2. Metabolism. Organisms require molecular machineryfor obtaining and transforming substrates to support contin-ual maintenance of internal structural integrity as well as forcopying and transcribing the molecular information.

3. Containment. Organisms are enclosed in structures(e.g., cell membranes and protein capsules) that maintain com-ponent proximity and functional linkages and additionally mayregulate external and internal concentrations of critical sub-strate and waste product molecules.

All three of these functional criteria must be met to sustainknown life forms, though they need not all be accomplishedwithin a single organism, as in most bacterial and eukaryoticcells, but may also be distributed across interdependent organ-isms, as in parasites and their hosts or in symbionts. Whetherthese processes are all necessary to account for the most gen-eral features of life—i.e., self-maintenance, self-reproduction,and evolvability—is difficult to determine. One difficulty de-rives from the absence of any exemplars of extraterrestrial lifefor comparison, making it difficult to discern essential fromincidental features due to environmental conditions and acci-dents of evolutionary history on this planet. Another difficultyis the absence of forms more primitive than even the simplestcontemporary life forms, which are far more complex thancould form spontaneously and which have apparently elim-inated many stages of simpler precursors. Finally, efforts toproduce artificial systems with these properties, but composedof constituents not found in organisms, are still in their infancy.So the range of possible alternative mechanisms is largely un-explored (but see Freitas [2004] for a thorough review of thestate of this research). These limiting circumstances make itdifficult to deconstruct living organisms for clues about therelative priority and independence of their various attributes,mechanisms, and substrates.

In recent decades, remarkable strides have been madein identifying the minimal components necessary for bacte-rial cell life. Approaches have generally been characterized astop-down versus bottom-up. Top-down approaches attempt toextrapolate backward, theoretically and experimentally, fromcurrent organisms to simpler precursor organisms. Prominentin this paradigm is the attempt to describe and produce “min-imal cells” by stripping a simple bacterium of all but its mostcritical components (Koonin 2000). Though considerably sim-pler than naturally occurring organisms, these minimal cellsstill contain hundreds of genes and gene products (Gil et al.2004) and so turn out to be vastly more complex than even

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Reciprocal Linkage between Self-organizing Processes is Sufficient for Self-reproduction and Evolvability

the most complex spontaneously occurring nonliving chem-ical systems, implying that they cannot be expected to haveformed spontaneously (Szathmary et al. 2005). The alterna-tive bottom-up approach attempts to generate key system-attributes of life from a minimized set of precursor molecularcomponents. An increasing number of laboratory efforts areunderway to combine molecular components salvaged fromvarious organisms and placed into engineered cellular com-partments called protocells (see recent reviews in Rasmussenet al. 2004; Szathmary et al. 2005). The intent is to producean artificial “cell” with the capacity to maintain the molecularprocesses necessary to enable autonomous replication of theentire system. To accomplish this, protocells must obtain suf-ficient energy and substrates and contain sufficient molecularmachinery to replicate contained nucleic acid molecules andto produce the protein molecules comprising this machineryfrom these nucleotide sequences, and probably much more (Gilet al. 2004). Though vastly simpler than what is predicted fora minimal bacterial cell, even the most complex protocell sys-tems fall considerably short of the goal of achieving persistentautonomous reproduction even though they incorporate morethan a dozen types of complex molecules (e.g., nucleic acids,complex proteins, nucleotides, phospholipids) which are al-ready organized into working complexes (such as ribosomes)by the living systems from which they have been removed.Given that they are composed of cellular components that ac-complish the relevant functions in their sources, it is expectedthat protocell research will accomplish its goal as more com-plex protocells are constructed. However, even the simplestprotocells currently being explored are sufficiently complex toraise doubts that such systems could coalesce spontaneously.

An implicit assumption of the great majority of theseapproaches is that replication and transcription of molecularinformation, as embodied in nucleic acids, is a fundamentalrequirement for any system capable of autonomous reproduc-tion and evolution. This is a natural assumption since nucleicacid–based template chemistry is the most ubiquitous attributeof all known forms of life. But including this attribute in anartificial cell turns out to be extremely demanding in terms ofcritical support mechanisms. In order to replicate nucleic acidsequences and transcribe them into protein structure, some oflife’s most complex multimolecular “machines” are required,and this is as true for protocells as it is in the simplest liv-ing organisms. Though some of these complications may beavoided by molecules serving multiple functions, such as thecapacity for RNA to also exhibit catalytic functions (Cech1986), an impressive number of complex molecular struc-tures and interactions must still be provided to support theseprocesses. Thus protocells are valuable test beds for exploringthe minimal conditions that are required for life, but leave muchunexplained when it comes to the origins of these conditions.As Szathmary et al. (2005) note: “[I]t is painfully obvious that

a great deal of molecular and protocellular evolution precededthe hypothetical ‘minimal cell’.”

In reaction to the dependence of nucleic acid functionon so many supportive processes, many researchers have ar-gued that supportive synthetic and metabolic process musthave evolved prior to nucleic acid functions (e.g., Morowitz1992; Kauffman 1993; de Duve 1996; Anet 2004; Andras andAndras 2005) and that structure-generating nonequilibriumprocesses may be more basic. Currently, the complicated in-terdependence between the construction and information func-tions of life, their relative priority in evolution, and their rolesin delimiting units of reproduction and selection have not beenresolved, much less the means by which these complex func-tional relationships might have initially emerged in the earlieststages of biogenesis (Maynard Smith and Szathmary 1995;Depew and Weber 1995; Hazen 2005).

Resolving the relationship between the informational andmaterial-formative aspects of life has also been an issue forevolutionary theory. Many definitions of evolution such asMayr’s (1988) “change in gene frequencies,” and generaliza-tions about natural selection such as Campbell’s (1960) “blindvariation and selective retention,” Dawkins’ (1976) “replica-tor selection,” and Hull’s (1980) replicator versus interactordistinction ignore the physical requirements of producing newcomponents and assembling them into larger dynamical com-plexes, focusing only on information replication and selectionprocesses.This abstract informational conception of evolutionhas become the default definition of a Darwinian process inany system (e.g., Hull et al. 2001).

Recently, computational approaches based on agent-based computer simulations have continued this tradition instudies of selection on reproducing algorithms. This work,broadly described as “artificial life” or A-Life (Langton 1989;Mitchell 1996), traces its roots to the pioneering analysis ofself-reproducing automata by the mathematician John vonNeumann (1966). His explorations of the logical requirementsof self-reproduction followed the insights of the then-newDNA genetics by conceiving of reproduction as an instruction-based process that could be modeled computationally. He ar-gued that a device capable of constructing a complete replica ofitself (which also possesses this capability) must include bothassembly instructions and an assembly mechanism capable ofusing these instructions to assemble a replica of itself, includ-ing the tokens encoding the instructions. Von Neumann andsubsequent researchers explored the formal requirements ofself-reproduction almost exclusively via simulation—e.g., incellular automata (Burks 1970)—because it was quickly rec-ognized that specifying a “kinetic” model of self-reproductionwith autonomous means for substrate acquisition and struc-tural assembly adds highly problematic material constraintsand energetic demands that rapidly expand the problem intothe realms of physics, chemistry, and mechanical design.

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Terrence W. Deacon

Computational simulations of evolutionary processes that ex-plicitly model both reproduction and phenotypic competitionalso tend to subsume the issues of component production anddynamical organization into abstract cost functions and selec-tion criteria (Holland 1962, 1975; Langton 1989; Ray 1991), asdo computational approaches to solving engineering problems(e.g., Fogel 1995).

Because abstract and computational investigations of evo-lutionary processes can ignore organism embodiment, theyrisk overlooking critical physicochemical constraints and af-fordances that lead to competition for resources and differen-tial reproduction among organisms. So, although the abstractlogic of natural selection may be multiply realizable (in thatit can be exhibited by both living and nonliving systems), se-lection is dependent upon substrate properties and how theyinfluence form generation. In nature, as opposed to in sil-ico, the final measure of selection—variation in reproductiveoutput—is a direct consequence of such material-energetic re-quirements. In this important respect natural selection is notmerely a formal process, but also a thermodynamic one (Fisher1930/1958; Schrodinger 1944; Prigogine and Stengers 1984;Swenson 1989; Ulanowicz and Wicken, 1989; Eigen and Os-watitsch 1992; Kauffman 1993; Pattee 1996).

The special importance of thermodynamic correlates ofliving processes was brought into sharp focus in the mid-20thcentury by the quantum physicist Erwin Schrodinger in hisinfluential monograph What is Life (1944). Along with hisseminal speculations about an aperiodic crystal-like basis forgenetic inheritance, he argued that the ability of organisms, andevolution in general, to resist the effects of the second law ofthermodynamics was a fundamental puzzle for physics. Whilealive, organisms maintain nonequilibrium conditions withintheir boundaries, countering internal entropy increase by ex-tracting energy from extrinsic sources. Phylogenetic evolutionfurther manages to not only conserve the orderliness embod-ied in organisms from generation to generation but to alsoproduce ever more structurally complex forms over time. Al-though these trends are produced at the expense of increasedenvironmental entropy, and globally produce an increase inentropy, their dynamics nevertheless stand in stark contrast tomost spontaneous physical processes.

In recent years, much attention has focused on the way thatvarious kinds of spontaneous order-producing dynamics con-tribute to countering the effects of thermodynamic degradationand increasing the global complexity and orderliness of livingsystems (e.g., von Bertalanffy 1952; Prigogine and Stengers1984; Eigen and Oswatitsch 1992; Kauffman 1993). Thesedynamical tendencies are broadly described as self-organizingprocesses and contribute to all levels of living systems, fromformation of complex multimolecular machines and organelleswithin cells, to generating complex segmentation and differ-entiation of embryonic structures, to coordinating complex

collective behaviors in social species (Camazine et al. 2001).The ubiquity of self-organizing processes in molecular biologyis one of the most distinctive characteristics of life (von Berta-lanffy 1952). In the nonliving world, self-organizing processesare comparatively rare and transient in comparison to processesin which features become progressively less organized. Theytend to be confined to subregions of larger systems wherenonequilibrium conditions transiently persist. But by virtue ofthe maintenance of nonequilibrium conditions within livingcells, self-organization of structure and function is ubiquitous.

Maintenance of life’s nonequilibrium milieu and construc-tion of its complex structures are dependent on two generalclasses of self-organizing molecular processes:

1. Autocatalysis: re-entrant cycles of catalytic reactions.2. Self-assembly: a process resembling crystallization

by which aggregate molecular structures spontaneouslycoalesce.

Autocatalysis occurs whenever each type of molecule ina set of catalysts augments the production of another memberof the set in such a way that eventually the formation of eachis catalytically enhanced by some other, resulting in a self-reinforcing circle (Kauffman 1986). The interlinked networkof catalytic reaction cycles that organize the flow of energy andthe synthesis of the critical molecular components in the cell isthus a complex form of autocatalysis. Self-assembly is a spe-cial class of molecular aggregation processes that occurs whenenergetically favored aggregations of molecular componentsspontaneously grow into large regular structures, sometimesincluding thousands of individual molecular constituents with-out external control or manipulation, so long as componentsare supplied (Crane 1950; Misteli 2001). Of interest for thisdiscussion are self-assembling structures that partition or con-tain space, such as the wide array of linear, tubular, and sheetstructures within living cells. These structures provide com-partmentalization, structural scaffolding, motility, and reliablelinkages of cells and cell components. This article will focuson a subset of self-assembling molecular structures that en-close space, such as those characteristic of viral capsules andtubular forms.

Both classes of cellular self-organizing molecular pro-cesses emerge from biased patterns of molecular interactionsthat result from allosteric complementarities and hydrogenbonding between large organic molecules. Although most cel-lular processes depend, to some degree, on contributions fromone or both of these self-organizing dynamics, they are com-monly considered ancillary to the genetic control of cellu-lar processes. Hence, the possibility that a more fundamen-tal contribution to the logic of life might be found in theirinterrelationship, irrespective of genetic information, has notbeen thoroughly explored.

This article calls attention to a complementarity in thedynamics of these two classes of self-organizing processes



that may hold the key to the spontaneous achievement ofself-reproduction in simple molecular systems. This comple-mentary relationship will be shown to have the potential togenerate more elaborated variants of self-reproduction dynam-ics, thereby challenging the primacy of molecular informationreplication as a necessary ingredient in the nonlife-to-life tran-sition.

A Model System

Both autocatalysis and self-assembly can be described as self-organizing processes in a general sense because of their self-reinforcing, form-generating dynamics, though each leads tomultiplication of structural regularities (of components andgeometry, respectively) via different thermodynamic mecha-nisms. Thus autocatalysis is a transient nonequilibrium pro-cess, whereas self-assembly is an entropy-increasing equilib-rium process. Under favorable conditions, autocatalysis canproduce a runaway local increase in the molecules compris-ing the autocatalytic set at the expense of other molecularforms. This increase in the local concentrations of membersof this set of molecules briefly counters the normal tendencytoward diffusion and admixture. Molecular self-assembly oflarge regular structures (effectively a special case of crystal-lization) occurs when component molecules’ complementarygeometries promote aggregation into lower energy regular tes-sellations or three-dimensional (3D) forms. Aggregation isself-perpetuating to the extent that the aggregation reducesintrinsic energy, and the symmetry promotes stability and cre-ates structural facets favoring additional component binding.Growth can be open-ended, as in crystalline formations ortubular structures, limited only by substrate availability andstructural stability, or it can be self-limiting, as in the case ofgeometrically closed structures such as the polygonal forms ofmany viral capsules.

Both autocatalysis and self-assembly contribute to thephysical implementation of von Neumann’s logical require-ments for self-reproduction in cellular molecular systems. Au-tocatalysis can by itself provide the iterated generation oflike components from like components, and self-assemblycan result in like components combining into large regular3D structures independent of extrinsic manipulation. Thus,although instruction and construction processes are widelyutilized in living cells, autocatalysis and self-assembly signif-icantly reduce the need for detailed instructional control anddedicated construction mechanisms. But can these be reducedentirely?

Outside of living systems, autocatalysis and self-assemblyare inevitably self-limiting and even self-undermining. Theycontinue so long as substrate molecules and free energy areprovided in immediate proximity, but they exponentially de-plete these conditions. Autocatalysis, in addition, is sensitive to

the collective proximity and concentration of all molecules ofthe autocatalytic set, which will tend to spontaneously diffuseaway from each other after synthesis due to normal thermody-namic admixture. Catalysis can also be blocked if catalytic sur-faces are occluded by being aggregated with other moleculesor if critical substrates are not freely diffusible. So molecularself-assembly can render molecules less catalytically reactivedue to immobilization and occlusion of surfaces. (However, itcan also facilitate multistage catalytic reactions in the specialcase where different bound catalysts are spatially organizedwith respect to specific reaction pathways and with their re-active binding surfaces exposed and aligned.) So these twogeneral classes of molecular processes are to some extent mu-tually exclusive.

However, autocatalysis produces one condition that isconducive to self-assembly—replenishment of the local con-centration of a self-assembling molecule—and self-assemblycan produce conditions conducive to autocatalysis—inhibitionof the diffusion and dispersal of complementary catalysts.

This reciprocity can be exploited if an autocatalytic cy-cle synthesizes a product molecule that tends to self-assembleinto a closed structure that limits diffusion (e.g., polyhedron,cylinder, etc., analogous to a viral shell). Such a linkage ofthese dynamics can generate a reliable higher order reciprocitybecause enclosure formation will be most prolific in the imme-diate vicinity of a supportive set of autocatalytic molecules.This will increase the probability that such a container willform around the molecules of the set required to make morecontainer molecules. Although by limiting access to new sub-strates, containment inhibits or blocks catalysis, it also main-tains proximity of interdependent catalysts. Thus, even thoughcatalysis is temporarily inhibited, containment increases theprobability that the potential for autocatalysis will persist,irrespective of temporarily slow reaction rates or local un-availability of substrates, so long as there is some probabilityof container rupture. When such a structure is disrupted orbreached, e.g., by agitation, in the vicinity of new substratemolecules, the contained catalysts are released, autocataly-sis recommences, and new catalysts and container-formingmolecules are synthesized in close proximity. Reconstitutionof the original configuration using some newly synthesizedand some old components, or formation of two or more repli-cas of the original, is likely to result. The decoupling fromimmediate local dynamics, achieved by containment, resultsin the intrinsic potentiation of future autocatalysis and, byextension, future container formation. Hence, the reciprocalcomplementarity of these two self-organizing processes cre-ates the potential for self-repair and even self-reproduction in aminimal form. While it might be argued that the requirement ofextrinsic disruption weakens the claim of “self-”reproduction,this process is reliably spontaneous and plays no substantiverole in generation of any constituent forms, making it more


Terrence W. Deacon

autonomous than reproduction in flowering plants that requireinsect pollinators.

A molecular system with these characteristics can becalled an “autocell” because it is self-enclosing and self-reconstituting. Although there are superficial resemblances tothe diverse classes of laboratory-generated structures calledprotocells (see below) and in other respects to “reversemicelles” with extrinsically bound reactive molecules (seeBachmann et al. 1992), it seems useful to distinguish auto-cells as a separate class of structures based on their combi-nation of three distinguishing criteria, two negative, and onepositive: a nonlipid, nonpermeable containment shell, lack ofself-replicating template components, and reciprocal cosyn-thesis of all components. An abstract depiction of the struc-ture of two general classes of autocells is provided in Figure 1.These classes are distinguished by containment geometry, i.e.,polyhedral (a) or tubular (b), and are patterned after the formsof viral coats and microtubules. Both are minimally simpleautocell systems, composed of only two classes of catalysts,one of which can self-assemble to form a container. A step-wise depiction of the component processes leading to for-mation of a polyhedral two-component autocell is depictedin Figure 2. More complex autocatalytic sets (including bothsynthetic and lytic processes) as well as more diverse con-tainment geometries are possible because autocell formationis a generic molecular system property that is independent ofspecific molecular constituents, and only dependent on theirrelative geometric correspondences. In abstract terms, the keyrequirement is a complete reciprocal coupling of a spontaneouscomponent production process and a spontaneous proximity-maintenance process that encompasses all essential compo-nents. (It is probably also critical for evolvability, discussedbelow, that this involves a multicomponent structure ratherthan a single molecule that merely catalyzes the formation ofmolecules like itself, i.e., a “naked replicator,” although I willnot defend this logical requirement here.)

The two classes of autocells depicted will have manyproperties in common, but will tend to differ due to containergeometry. The finite regular geometry of polyhedral autocellswill determine fixed component numbers (though some polyg-onal structures, e.g., triangles, can assemble into a number ofpolyhedral forms) and a corresponding cycle between growthand stasis. Tubular autocells, analogous to microtubules orthe tobacco mosaic virus coat, have the potential for contin-ual growth, though mechanical forces will make longer tubesproportionately more fragile.

However, although tubular autocells are not geometricallyclosed containers, molecular surface forces within the tubewill likely impede motion of contained molecules along itslength, thus making it an effective barrier to diffusion, andincreasingly so with greater length. Both polyhedral and tubu-lar autocells will require extrinsic forces to break them, and

a

b

Figure 1.Two general classes of autocells are depicted as geometric constructions.An autocell produced by polyhedral containment is depicted in (a) and anautocell produced by spirally elongated tubular containment is depicted in(b). Both are minimal autocells to the extent that each is constituted by onlytwo catalysts (C and F in both). Catalysts are also depicted as synthesizedfrom two substrate molecules in each case (A and B and D and E in both),though only in (a) is there any indication of the shape complementaritiescontributing to catalysis and self-assembly. Autocatalytic cycles are depictedwith arrow diagrams for each (using letters in [a] and component shapes in [b]).A polyhedral autocell completely encloses the complementary catalyst andachieves structural closure, allowing no further growth. A tubular autocell doesnot completely enclose its interior, but contained molecules are retained byviscosity of van der Waals interactions with the inner walls. Tubular autocellsalso retain the ability for continual elongation. Reproduction in both casesdepends on extrinsic forces to break containment.

thus to reproduce, but this will be less of a disruption of struc-tural integrity for tubules where growth will recommence atthe newly exposed ends, with the local release of containedcatalysts. The constraints on molecular geometry are also lessrestrictive for spirally assembled tubes than for polyhedrons,making this form likely easier to achieve in the laboratory as



Figure 2.Idealized depiction of component steps of autocell formation involving a min-imum number of catalytic components (N = 2) and polyhedral containment.Substrate molecules (1, 2, 4, and 5) are identified in (a) and synthesized cata-lysts (3 and 6) are identified in (a) and (b). The interactive allosteric shapes ofthe molecules are abstractly depicted as a generic space-filling shell (shownwith a phantom appearance in [d] and [e]). These allosteric relationships aredepicted as facilitating covalent bonding (arrows to bright atoms in (d) and (e))to form autocell catalysts 3 and 6. Self-assembly of molecule 6 into polyhedralshells by edge binding and the encapsulation of nearby catalysts of type 3 ([f]and [g]) creates autocells (h) that are subject to dispersion as discrete units ofreproduction and loci of selection.

well as by serendipitous processes in nature. Although tubu-lar autocells will differ in length, and thus are intrinsicallymore variable, their defining composition will be essentiallythe same irrespective of length.

Both types of autocell exemplify in molecular terms—and with considerably more simplicity and compactness thanpreviously envisioned—von Neumann’s minimal descriptionof self-reproduction: reproducing a replica with the physicalcapacity to similarly reproduce itself. This is in part possi-ble because they do not include what von Neumann calleda “universal constructor” (able to use instructions to buildany specified machine), but only a single-product construc-tor mechanism. Significantly, autocells achieve reproductionof a characteristic unit-form without an instruction compo-nent and without the separate instantiation of the construc-tion component of von Neumann’s automata. Despite theircapacity to self-repair and self-reproduce, however, autocellslack a majority of mechanisms and constituents that are pre-sumed to be essential for living cells or even viruses, and sothey do not qualify under any current definition of life. Au-tocellularity may even be achievable with entirely inorganicconstituents.

Although autocell chemistry is currently only speculative,its feasibility should be easily verifiable in the laboratory. Thecomponent chemical processes required for autocell formationare all well understood and, despite the combined constraintson molecular symmetries required for both autocatalysis andcontainer self-assembly, the generality of this logic is inde-pendent of molecular composition, providing a vast array ofpossible constituents to choose from. Their practical plausibil-ity warrants consideration of one further extrapolated property:a potential to evolve.

Autocell systems also fulfill the three abstract criteria forevolvability (even if not natural selection in the strictest neo-Darwinian sense):

1. Self-reproduction with fidelity. Autocells are capableof continuous self-reproduction, and so are potential progeni-tors of lineages. The necessary synergies between componentsguarantee a high degree of fidelity in this process even withouttemplate replication. Because of the holistic character of auto-cell reproduction, however, fidelity will likely be increasinglydifficult to maintain as autocell complexity increases, and mayserve as a constraint on complexity. An autocell lineage willincrease in numbers so long as there are sufficient substratemolecules in the surrounding environment, energy to drivecatalysis, and conditions that periodically disrupt autocell in-tegrity (e.g., agitation).

2. Competition for resources. Lineage propagation willresult in competition between lineages for the substratemolecules required for reproduction. Autocell lineages thatarise from the same ancestor or otherwise share similar chem-ical properties (e.g., due to arising from similar initial con-ditions) will propagate at rates correlated with their relativesuccess at garnering the same (or catalytically similar) sub-strate molecules from a finite pool.

3. Heritable variation. Although autocells tend to re-establish the molecular configurations predisposed by themolecules inherited from progenitors, this must occur via par-tial breakup and re-enclosure. This makes incorporation ofother molecules from the local environment a high probabil-ity. Autocell components are thus susceptible to substitution bycatalytically similar molecules and are capable of propagatingthis change to a future lineage so long as appropriate substratescontinue to be available. Incidentally, incorporated moleculesthat exhibit catalytic interaction with existing components soas to become insinuated into the cycle of autocatalysis willbe regularly synthesized. To the extent that these heritablestructural variations augment reproduction they will producelineage-specific propagation advantages. Differential lineagepropagation will be a function of correspondences betweenthe requirements for reproduction and features of the surround-ing molecular and energetic environment.

These features qualify autocell lineage evolution as ageneric form of natural selection, despite the absence of


Terrence W. Deacon

separately transferred information-bearing units, and eventhough this blurs the distinction between Weismannian andLamarckian inheritance. So, even though autocells lack manypresumed core attributes of life, they satisfy both the materialand the logical conditions for self-reproduction and evolutionin a minimal sense. Autocell dynamics demonstrate that thesefundamental attributes of life can emerge without the pre-sumptive critical and ubiquitous role of separate information-bearing molecules; for example, nucleic acid polymers func-tioning as templates. But it may also provide a new context forexploring the origins of these functions. For example, tradeoffsbetween replication fidelity and complexity, while limiting au-tocell evolvability, may contribute the most significant selec-tion pressures favoring transition to template-based processes.This creates a context for asking how template-based informa-tion functions might have evolved from functionally distinctantecedents, i.e., in an autocell ecology. If autocell evolvabil-ity is sufficient to reach this level of complexity then otherproperties of nucleic acid components (e.g., the phosphate ac-cumulation and transfer roles of nucleotides, or polymerizationas a means of energy storage, etc.), which could contribute toautocell evolvability, become important clues to the evolutionof molecular information functions (see discussion below).

Discussion

Comparison with Other Protolife ModelsThe autocell model exhibits similarities with previous sys-tems invoked to explore the origins of life. Probably the mostcomparable model systems were described by the Hungarianchemist Tibor Ganti in 1971 (although his work became avail-able in English only in 2003). Ganti’s purpose was to outlinea theoretical chemical logic for defining life. He describeda theoretical chemical system, which he called a “chemo-ton,” that he believed embodied the minimal conditions foran entity described as living. A chemoton is an autocatalyticsystem composed of three coupled autocatalytic cycles: onethat captures energy, one that produces a cell membrane, andone that replicates molecular information in a template-codemolecule (for specifying the other parts of the system). Likethe autocell, Ganti’s chemoton is a theoretical chemical sys-tem. But it is considerably more complicated than an autocell,involving a large number of different types of molecules allarranged into complicated interdependent chemical reactioncycles. This complexity is the result of requiring that thechemoton mechanism include semipermeable containment,continual metabolism, and information replication, in orderto abstractly model life in its current forms. Because theautocell model does not attempt to exemplify the necessaryand sufficient conditions for life in general, only those suf-ficient for self-reproduction, each of these three criteria ispotentially dispensable.

Ganti’s chemoton is more similar to an autocell than aprotocell (see below), however, in that emphasis is given onthe reciprocity and synergistic coupling of the chemical pro-cesses involved rather than on any specific substrate, reac-tion, or combination of elements. Yet, although the chemotonmodel does not necessarily require the equivalent of DNAreplication and template function, it does assume that someform of molecular information transmission is involved. Incontrast, the autocell model demonstrates that reproductionand self-maintenance can be achieved at least in minimal formwithout a separate information replication cycle. Although adistinct replication of an encoded representation of the essen-tial structural–functional relationships may augment replica-tion fidelity and evolvability, it is not a necessary prerequisitefor these properties. Ganti considered the incorporation of aninformation replication cycle as an “absolute life criterion” be-cause it was deemed necessary for “unlimited inheritance.” Butalthough the holistic replication of autocell structure affordsonly limited inheritance, this limitation is ultimately merelydefinitional. If autocell evolvability is sufficient to achieve thelevel of complexity sufficient for the emergence of template-supported replication, it is justifiable to argue that autocelllineages have the potential to achieve unlimited inheritance.

Ganti explored this issue by contrasting the chemoton toa simpler model chemical system that is more closely analo-gous to autocells. Ganti called it a “self-reproducing spherule.”It consists of an autocatalytic cycle that produces an enclos-ing lipid membrane. He assumed that the membrane wouldneed to be semipermeable in order to support ongoing cataly-sis, that the spherule would continually grow, adding catalystsand lipid molecules, and that reproduction would occur viagrowth and subdivision by virtue of the rapid overproduc-tion of membrane molecules producing structural instability.These properties are significantly more elaborate and imposeconsiderable obstacles to spherule design in comparison to au-tocells. This is because achieving autonomous lipid synthesisand providing mechanisms for membrane growth and espe-cially selective membrane permeability do not have obviousprebiotic solutions. Also lipid membrane containment is struc-turally amorphous and lipid vesicle subdivision is not coupledwith systematic distribution of contents to “offspring” (so whatconstitutes an individual’s identity is unclear). These featuresare effectively forced on Ganti’s model by two design criteria.The first is his assumption that autocatalysis would need tobe continuous, whereas the autocell cycles between catalysisin the disrupted state and inertness in the enclosed state. Thesecond is the relatively passive role of the lipid membrane con-tainer with respect to component replication, spherule division,and re-assembly; whereas autocell containment molecules andcontainers are coformed along with supportive catalysts. Asin the autocell, catalysis in the spherule provides morphologi-cal constraints on incorporation of variant components across



reproductions, but lipid membrane formation is primarily afunction of hydrophobic polarity, and is only minimally con-strained by stereochemical binding geometry. In a commentaryincluded with the English translation of Ganti’s work, EorsSzathmary (2003) points out that cell membranes are capableof a form of “structural inheritance” of acquired character-istics (Jablonka and Lamb 1995) where atypical moleculesincorporated into the membrane can be passed to daughtercells (analogous to inheritance of membrane modifications inParamecium). Since neither membrane components nor mem-brane structures are directly involved in the structural repli-cation of these spherules, inheritance of structural defects inmembrane form is not productive and new replicas of thesevariants are not reproduced. Such passively inherited struc-tural variants are subject to rapid diminution in the lineage,and are thus of finitely limited heredity. These features followfrom the fact that the enclosing lipid membrane is formed fromside-products of the autocatalytic synthetic processes and donot contribute to reproduction of other components.

In contrast, all components of an autocell’s catalytic andself-assembly processes are directly involved in replicating itsglobal form. Because neither the unbound contained catalystsnor the bound catalysts constituting the container are outsidethe synthetic process, all acquired substitutions are potentiallyreproducible and not merely by passive structural inheritance.This provides a primitive precursor to the information thatmaintains organizational identity across replications in liv-ing cells, by providing reciprocal replication of any potentialcomponent. So even though inheritance is still structurallyconstrained, there is no theoretical limit to alteration of thesefeatures over the course of lineage evolution. The temporarilyinert state of a closed autocell further aids in the maintenance ofstructural identity across reproductions, by limiting the poten-tial dissipating effects of side reactions in autocatalysis, sinceenclosure stops catalysis, maintains catalytic set proximity,and maximizes content homogeneity due to the collocation ofthe highest catalyst concentrations and most rapid containerformation.

So despite the considerably more complex requirementsfor creating a self-reproducing spherule, Ganti’s spheruleswould still have more limited inheritance than autocells andtheir “progeny” would be far less consistent in structure. Auto-cell dynamics, in contrast, demonstrates that not all of Ganti’s“absolute criteria for life” are essential for either open-endedself-replication or the potential of open-ended heritable modi-fication that evolution requires. In this way, the autocell modelprovides a further simplification that fills an important gap intheories of the emergence of life.

The autocell model is even more divergent from mostprotocell models. Though some authors apply the term pro-tocell generically to any protolife system, this obscures manyimportant distinctions. The architectures of the various pro-

tocell systems are based on a backward extrapolation fromexisting living systems. Morris (2002) defines protocells as“Darwinian liposomes-bilayer vesicles with mutable on-boardreplicases linked to phenotypes.” Most exemplars include fourcharacteristics, presumed essential, that distinguish them fromautocells: (1) replication of nucleic acid molecules (or relatedmolecules with analogous function); (2) mechanisms to facil-itate their replication; (3) containment within a lipid vesicle;(4) growth and fissioning of the enclosing vesicle in a way thatdistributes replicated nucleic acid molecules and replicativemechanisms to the daughter vesicles (Rasmussen et al. 2004).Simple “protocells”have been synthesized in the laboratoryand are currently being explored for their potential to self-replicate (Szostak et al. 2001). One of many critical remainingchallenges includes supplying protocells with energy to drivecontained synthetic and replication reactions. Both energy andsubstrates must be continuously available if continual open-ended reproduction is to be possible, because protocells areconceived as maintaining a continuous nonequilibrium state.Clearing this last hurdle adds considerable difficulty and com-plexity. In most current protocell models, molecular informa-tion replication is presumed to be a critical requirement whilereciprocal interdependence between information replication,component production, and reproduction-enclosure processesis bracketed from consideration and often must be extrinsicallyregulated. This incomplete coupling distinguishes the designlogic of protocells from both chemoton and autocell models.

Although the autocell model also focuses on containmentand molecular replication, it is their dynamical interdepen-dence that defines it. Autocell self-repair, self-reproduction,and structural conservation require no special class of repli-cator molecules and are not dependent on additional quali-fications on containment, such as the capacity for selectivetransport of substrates and waste products, or the capacityfor continual growth and correlated fission (though these lat-ter two features may be a spontaneous attribute of tubularautocells). The comparative simplicity of the autocell cycleis aided by the inertness of the completed structure, whichdoes not require substrates for self-maintenance or possibleself-reproduction unless disrupted, and then only transiently.The requirement for gaining open-ended access to substratesis accomplished by alternation between inert closed and cat-alytically active open phases. In terms of both informationreplication and metabolism, autocells are not alive, althoughanalogies to viruses and bacterial spores suggest themselves.Moreover, even reproduction must be extrinsically initiated,even though the potential to compensate for structural disrup-tion and to produce replicas that maintain their structural anddynamical identity are intrinsic properties. Autocells arefor this reason somewhat intermediate between passiveequilibrium-seeking crystalline growth processes and liv-ing processes. They counter spontaneous degradation by


Terrence W. Deacon

spontaneous reconstitution, replication, and stabilization ofa configuration that embodies these capacities. Rather thanmaintaining themselves in a persistent nonequilibrium statethey cycle between brief phases of nonequilibrium dynamicsand extended phases of inert potential; providing a ratchet-likepreservation of the consequences of self-organization. Andrather than depending on molecular templates for componentreplication and structural memory across reproductions, theytake advantage of the stereochemical specificity of catalysisand the geometric specificity of self-assembly, as well as fromthe attractor dynamics of these two self-organizing processes,to maintain and replicate structural identity.

Constraints on Spontaneous Autocell FormationBecause of its relative simplicity the autocell model suggestsa much wider range of approaches to the mystery of the emer-gence of life, extending insights suggested by complex sys-tems approaches(Kauffman 1993; Depew and Weber 1995).These approaches have shown that, for example, the prob-ability of spontaneous autocatalysis is non-negligible in en-vironments containing a sufficient diversity of catalyticallyinteractive molecules (Farmer et al. 1987). The autocell modeladditionally shows how some of the barriers to sustained auto-catalysis (e.g., catalytic set diffusion and set degeneration dueto side reactions) may be partially mitigated by alternation be-tween a brief catalytic phase and a contained inert phase. Ingeneral, self-assembly dynamics is possible in a wide varietyof molecular systems, and the special variants that could leadto self-assembly of simple molecular enclosures are thereforenot likely to be highly improbable. Indeed, many forms ofself-assembling molecular enclosure mechanisms have beenexplored by chemists interested in nanotechnology applica-tions of these processes (see, e.g., Padilla et al. 2001), andcould potentially lead to laboratory-based autocell systems.The fact that these two classes of chemical processes are nei-ther exceedingly rare, chemically complex, nor confined to avery limited class of molecular types makes their spontaneouslinked coincidence a plausible scenario for the emergence ofprotolife, from a cosmic perspective.

But although autocell evolution is potentially unlimited, itis highly constrained. Because the repair and replication of theglobal organization of an autocell is accomplished entirelyby virtue of molecular structure complementarities, evolv-ability is limited in comparison to living cells or protocellsthat synthesize their components from simpler building blocks(e.g., amino acids) by way of template molecules. Lackingtemplate guidance of polymerization, autocells will be highlyenvironment-specific, depending on a highly limited class ofspecific substrate molecules of sufficient size and structuralcomplexity to be catalytically active. More significantly, thespontaneous emergence of autocellularity in a prebiotic en-vironment likely requires three unusual conditions: (1) the

presence of significant quantities and concentrations of largepolymers; (2) some considerable degree of structural similarityamong these molecules; and (3) sufficient variety and degener-acy of their stereochemical properties to support spontaneousautocatalysis and self-assembly. The spontaneous nonbiogenicproduction of large numbers of structurally similar moleculesof appropriate size for effective catalysis is presumed to beunlikely on the prebiotic earth, even if not an issue in thelaboratory. Nor is it easy to determine how wide a range ofconditions might be conducive to spontaneous autocell for-mation, because of the vast range of possible molecular formssusceptible to both catalytic interaction and self-assembly pro-cesses and the nonlinear interdependence of the geometric andenergetic conditions enabling reciprocity of both processes.However, because of their relative simplicity, these require-ments for the emergence of autocells are almost certainly farless constraining than for the spontaneous formation of eventhe simplest self-reproducing protocells, or even Ganti’s self-reproducing spherules.

Even so, the requirements for spontaneous autocell forma-tion are significant. If these conditions are not spontaneouslyachievable in at least some abiotic conditions, an autocellscenario for the origins of life (or protolife) is not plausi-ble. Indeed, the prior availability of suitable macromoleculeshas long been considered a serious stumbling block for alltheories of the origins of life. Even the spontaneous prebi-otic synthesis of the component monomers of the most im-portant of life’s molecules—amino acids, sugars, nucleotides,phospholipids—has been difficult to explain. Classic experi-ments provided evidence that some amino acid synthesis couldbe achieved spontaneously from simpler precursors, such aswater, methane, ammonia, and carbon dioxide, presumed atthe time to be components of the primitive earth atmosphere(e.g., Miller 1953; Oparin 1961; Miller and Urey 1959). Butmany other relevant building blocks remain difficult to explain,and an abiotic mechanism for polymerization of amino acidsinto peptides is believed to be unlikely in the prebiotic earthenvironment (Maynard Smith and Szathmary 1995).

Extraterrestrial Sources of Autocell ConstituentsIf we are willing to look beyond the context of the prebi-otic earth, however, we may find that certain of these limitingconditions may not be so unlikely. For example, there maybe an alternative to the amino acid polymerization problem.There is evidence that in quite different extraterrestrial en-vironments (such as the gaseous surface of gas giants likeJupiter), polymers of cyanide (e.g., HCN polymers such aspolyamadines) may be formed by spontaneous dehydrationreactions (Matthews 1975, 1997). Given the scale of this envi-ronment this might provide vast quantities of large polymers. Ifcatalytic interactions are possible in Jovian-like atmospheres,autocell evolution could be occurring extraterrestrially on a



massive scale. More importantly, significant amounts of Jo-vian polymers could have been transported (e.g., via cometarytransport) to rocky planets of the inner solar system whereaqueous conditions would be available (like Mars or Earth).This is important, since HCN polymers have been shown tospontaneously hydrolyze to form heterologous peptides inaqueous environments (Mathews 1975). This lends renewedsupport to a “polymers first” scenario for prebiotic chemicalevolution that would be suitable for the emergence of autocells.

Such prebiotic peptides would likely deviate from thoseproduced by contemporary organisms in many respects. Forinstance, without template coding favoring linear polymer-ization, the polymers formed under such conditions wouldlikely be more structurally diverse and irregular, even if not aslarge as organic proteins, because of the presence of branchedrather than predominantly linear architectures. Also, with-out template-guided constraints on polymerization, intrinsicchemical reaction biases would play a much more prominentrole in determining molecular structure. This would resultin far more homogeneity in the general size and structureof these polymers than is found in organic proteins. Theseare potentially advantageous biases. An environment suppliedwith modest concentrations of structurally similar 3D complexpeptide-like polymers would be ideal for autocell formationand evolution. It even suggests the possibility that lytic ratherthan synthetic reactions (such as those modeled above) couldhave been the basis for the first stages of autocellularity—a condition that would also be energetically more favorable.Thus, polymeric molecules in sufficient concentrations, diver-sity, and catalytic capacity might have been available on theprebiotic Earth and Mars to initiate and sustain autocell evo-lution. Additionally, transport to an inner rocky planet wouldexpose these molecular systems to minerals and metals likeiron, phosphorus, sulfur, and so on, which would provide sig-nificant aid for energy-demanding catalytic reactions.

So despite these potential caveats, autocell formationshould be possible in conditions that are far more variablethan those of ancient or modern earthly environments. Moreimportantly, it may be realizable using molecular substratesradically unlike peptide polymers. Assuming that the coinci-dence of reciprocal coupling of the few stereochemical rela-tionships necessary to support autocell formation is even min-imally probable in some naturally occurring conditions, thesubstrate-independent realizability of autocellularity shouldmake this form of molecular organization far more prevalentthroughout the universe than anything resembling earth-basedlife. Given the probability that the formation of other planetarysystems will follow similar rules in similar galactic conditions,planetary systems with similar stratified organization of plan-ets and chemical compositions should be common. Thus, ifspontaneous autocell formation is even weakly probable insuch conditions we should expect that highly similar auto-

cell forms could arise independently in vastly separated starsystems.

Implications for General BiologyThe probability of spontaneous autocell formation in this orany solar system is, in an important sense, irrelevant to decid-ing whether this form of molecular system is comparable insome way to living organisms. Even if spontaneous autocellformation turns out to be so unlikely that its production isconfined to the highly controlled conditions obtainable only inlaboratory settings, the self-repair and self-propagating prop-erties of such synthesized autocells will still make them farmore comparable to organisms than to all other forms of abi-otic chemistry.

This functional affinity warrants the designation of a su-perordinate classification scheme that would recognize theaffinity of autocells with organisms. To designate the en-tire class of self-reproducing chemical systems susceptibleof evolution (including autocells, living organisms, and pos-sibly other forms with these features) I propose the term Au-taea (named for their bounded autonomy and self-supportivedynamics). This would serve as a grand classification of formsdefining the basic units of a general biology.

But a classification that recognizes an autocell-life affinityshould not be confused with phylogenetic taxonomies basedon common ancestry. It is a classification based on analogousfunctional organization. As such it would not be an alternativeto lineage-based taxonomies, but an orthogonal classificationscheme. Thus, similarly organized forms arising in causallyand chemically isolated contexts (such as in separate star sys-tems or laboratories) may be distinguishable into distinct par-allel grades of functional organization. Although such a classi-fication may not appear to offer an immediately useful schemefor organizing life forms, it may nonetheless help to highlightnonphyletic formative principles that may illuminate aspectsof biological organization that would otherwise go unnoticed.

The intermediate status of autocells between life and non-life suggests an important organizational dichotomy that canbe recruited for further classification purposes: mode of struc-tural reproduction. Autocell functional-continuance and repro-duction is maintained solely by the highly constrained mor-phological limitations of the stereochemistry that enables thewhole ensemble of components to converge to a highly lim-ited stable structure. This form of reproduction can be char-acterized as holistic, ensemble-, and attractor-based, in theterms of the classification of replication processes proposedby Szathmary (1999, 2000). All modern organisms (includingviruses), and hence presumably also their common ancestor,are organized around indirect template-based specification offunctional components and the template-code substrate is se-questered from other phenotypic interactor roles. This providescoded reproducers with unlimited heredity. So, while there


Terrence W. Deacon

may be many plausible variations on the logic of reproduc-tion, probably the most critical feature separating autocell-likesystems from life involves the presence or absence of templatecoding for form-producing processes.

In this regard, we can describe autocell repair and prolif-eration as “morphological reproduction” and coded synthesisof components from a replicated template as “coded repro-duction.” Morphological reproduction is distinct from mere“structural inheritance” (see Jablonka and Lamb 1995) in thatit is actively replicated in autocell reproduction rather than pas-sively inherited as are, for example, membrane abnormalitieswhen cells divide. The distinction between morphological andcoded reproduction is not categorical, however. While autocellreproduction is directly dependent on morphological corre-spondence relationships between molecules, coded reproduc-tion is ultimately just a more complex and indirect version ofthis. The nucleotide code relationship of living systems can bedecomposed into a number of reciprocally linked morpholog-ical reproduction processes. Both DNA–DNA replication andDNA–RNA replication can be described as morphologicallybased replication in which complementary molecular geome-tries constrain precise molecular interrelationships. Likewise,the ribosomal process that maps mRNA sequence morphol-ogy to amino acid sequence morphology is also dependenton linked morphological matching relationships: that betweenmRNA and tRNAs. Finally, the polar orientation of the amineand acid poles of amino acids that are conducive to peptidebonding, irrespective of other residues, completes the insula-tion of one form-form matching process from another so thata code-like arbitrarity is possible.

The morphological modifications of nucleotide sequences(e.g., via point mutation) are consequently subject to chem-ical and functional constraints that have little in commonwith linked morpho-functional chemical properties of proteinshape. The resulting chemical arbitrarity of linking morpho-logical reproduction mechanisms provides considerable ad-vantages for evolvability. This hierarchic dependence suggeststhat direct morphological replication is ultimately primitivewhile indirect coded replication is evolutionarily derived fromit. The priority of morphological component reproduction isalso exemplified by the fact that all living cells and viruses de-pend on morphologically reproduced components in additionto nucleic acid based syntheses. Prion protein reproduction isthe only entirely morphologically based replication processknown associated with living systems. But a prion is not onlyentirely parasitic on the neuronal synthesis of specific precur-sor preprion proteins, it only imposes its morphology on theseprecursor molecules and contributes nothing in the way of newcomponents.

The logic of this hierarchic dependence of forms of repli-cation can be summed up by noting the obvious generalizationthat information replication inevitably entails form replica-

tion. A similar point is made by Szathmary (2000) when heargues that evolution tends to develop from holistic to modularand phenotypic to genotypic replication, and so on. Therefore,some form of morphologically based reproduction of compo-nents is a logical requirement that must be operationalized atsome level even in A-Life simulations.

Using these criteria, then, we can delineate a superordi-nate classification of possible forms of life-like systems andtheir probable simpler antecedents. Two major organizationalgrades can be distinguished based on mode of reproduction.I propose the term Semeota (from seme, sign; named for thesemiotic basis of organism replication and identity) for theclass of all organisms that use molecular coding in order to syn-thesize components and reproduce, as do all terrestrial organ-isms and viruses. I propose the term Morphota (morphology-based systems) for the class of organisms that is generatedand reproduced by way of the constraints of molecular mor-phology alone. As the above analysis suggests, Semeota willinevitably be a derived offshoot from Morphota in a givenplanetary context. But by virtue of the vastly increased evolv-ability of Semeota, and their capacity to break down and re-construct molecules to suit their needs rather than rely on theirabiotically synthesized availability, the evolution of templatecoding is expected to create conditions that eliminate mostMorphota. Nevertheless, Morphota might continue to predom-inate in harsh conditions owing to their relative simplicity andreduced environmental constraints.

Of course, if a form of autocell evolution is possible, theautocell forms described here are only the simplest types ofMorphota. Many more complex forms of noncoded reproduc-ers are likely possible, which may incorporate semipermeablemembranes, continual exchange of substrates and waste prod-ucts, separation of energy capturing and energy utilizing chem-ical processes, and continual maintenance of nonequilibriumchemical dynamics. In other words, there may be considerableroom for intermediate evolutionary stages between simple au-tocellular Morphota and Semeota. More importantly, giventhat template-based coded reproduction (such as in terrestrialorganisms) is composed of reciprocally interdependent mor-phological reproduction processes (as described above), anevolutionary pathway from simple morphological reproduc-tion to coded reproduction is effectively a logical requirementthat must be realized in any evolutionary sequence leading tocoding. This offers a research program within which we canbegin to explore the evolution of coded reproduction systemsand the origins of the complex heteropolymers (e.g., nucleicacids) that serve as templates.

A speculative scenario can illustrate this possibility. Inliving cells, for example, nucleotides serve a dual role asenergy-ferrying molecules and template building blocks. Thisduality might reflect an antecedent form of Morphota inwhich various forms of nucleotides provide energetic support



for catalytic reactions, and where nucleotide polymerizationserves as a means of “storing” deactivated nucleotides dur-ing “dormant” phases. Such relatively unreactive nucleotidepolymers would thus be available for subsequent exaptation astemplates. The origins of nucleic acid chemistry could thus turnout to involve a complex evolutionary sequence of stages bothbefore and after the advent of template functions. Laboratoryexploration of autocellular systems could thus be a critical toolfor exploring this currently ubiquitous informational characterof life.

The possibility of autocell forms incorporating nucleicacid polymers, even if not involved in template functions,opens the door to some potentially radical possibilities for theorigins of cellular versus viral forms of Semeota. It is generallyassumed that viral forms evolved as fractionated derivativesof cellular systems, because of their dependence on cellularmetabolism for production of viral constituents from viral nu-cleic acid templates. But it is possible that this dependencecould have evolved subsequently and that some viral formscould trace their ancestry to Morphota that did not originallyhave a coding link between their nucleic acid polymers and en-capsulation molecules. The absence of autocatalytic formationof components in known viruses argues against this scenario,but a plausible argument could also be made for subsequentloss of this function to far more efficient cellular alternativesdue to parasitism. So we cannot conclude that all remnants ofsuch a prebiotic evolutionary phase are extinct.

There are also obvious implications for astrobiology. Themultiple realizability of this molecular organizational logic,and the wide range of planetary conditions likely conduciveto formation and persistence of Morphota, but not Semeota,suggests that astrobiologists might consider looking for thevery different chemical and structural signatures that wouldbe left by Morphota. These might include anomalous con-centrations of highly similar polymers and microfossils of vi-ral dimensions and with regular molecular structures that arecharacterized by enclosed volumes. The discovery of tracesof morphotic evolution on other planets in our solar systemwould radically reorient thinking about prebiotic terrestrialchemistry.

Finally, the simplicity and generality of the autocellmechanism also offers a new class of laboratory model sys-tems that can be exploited for their special life-like proper-ties. Laboratory synthesized autocells would not necessar-ily be limited to forms related to life or composed of or-ganic molecules. Given the highly generic criteria that mustbe met to achieve this result, engineered autocell-like sys-tems can probably be composed of highly diverse substratesarranged in combinations that could never occur sponta-neously. For example, autocells formed of inorganic molec-ular substrates could combine autocellular self-assembly, self-repair, and self-reproduction properties with other electrical,

chemical, or even nuclear properties of these materials to pro-duce functions quite different than anything found in life.These life-like behaviors are also of considerable relevancefor practical applications in the growing field of nanotech-nology. Molecular containers that can be induced to sponta-neously replicate and encapsulate surrounding molecules andthen release them again under controllable conditions couldhave numerous uses, from molecular cleanup and storage totargeted drug delivery. However, the most intriguing propertyof engineered autocell systems would undoubtedly be the po-tential to develop special variant forms by directed evolution.Achieving a nanodesign strategy that, instead of prespecifyingits products, directed their evolution by the controlled modifi-cation of their environment—perhaps incrementally converg-ing toward a target application context—would be the HolyGrail of nanotechnology.

Conclusions

Although no autocell has been produced in the laboratory oridentified in nature, and many chemical kinematic issues havebeen overlooked which could make their physical realizationquite difficult to achieve, they offer a useful model system forexploring the minimal physical requirements for self-repair,self-reproduction, and evolution. Their plausibility and sim-plicity demonstrates that these core attributes of life likelyderive solely from a reciprocal coupling of mutually reinforc-ing self-organizing dynamics. In abstract terms, this involvesa reciprocal coupling between a component production pro-cess (autocatalysis) and a component proximity-maintenanceprocess (enclosure self-assembly). These criteria can likelybe achieved in diverse ways besides those presented here. Itis the higher order synergy of these processes—not mere en-closure of self-replicating entities—that creates the necessaryand sufficient conditions for the emergence of these funda-mental biological properties. This insight fills in a missinglink joining nonequilibrium thermodynamic processes to self-reproduction and evolutionary processes. The basic principlesinvolved should be capable of further extension to systemswell beyond the molecular chemistry of life.

AcknowledgmentsGraphic art in Figure 2 by Gautam Rangan, Brandon Jacobs, and Jason Gatt,from a computer-generated animation (electronically available on request).This work has been greatly aided by suggestions and comments from J.Sherman, T. Cashman, J. Ogilvy, U. Goodenough, and J. Hui.

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Reciprocal Linkage between Self-organizing Processes is ... · ited form of evolution, capable of leading to more efﬁcient, more environmentally ﬁtted, and more complex forms