The Emergence of Self- Rectification Why Self-Organization Can’T Explain the Origins of Life

The emergence of self- rectification Why self-organization can’t explain the origins of life

Terrence W. Deacon U C Berkeley

A lecture presented Nov. 24, 2014 to the Origins Institute, McMaster University, Ontario, CA Abstract: In many fields it is now common to hear the concepts of emergence and self-organization treated synonymously and for theorists to claim that self-organization explains the emergence of the special properties exhibited by organisms and experienced by conscious beings. In this presentation I will show why this is insufficient—though relevant—for explaining the emergence of these phenomena. I will offer a critique of current mathematical and biochemical approaches to the origins of life that focus on the self- organizing or replicative functions of life as primary, respectively. The key missing step is to show how systems of linked self-organizing processes can potentiate and limit one another in a way that creates substrate-transferrable formal constraints that channel work to prevent their own degradation and error accumulation. This perspective can radically enlarge the domain we define as alive and it suggests very different contexts for its origin. Thinking outside the (reductionistic earth-life) box

RNA-world, DNA, cells, water, self-organization, replication, natural selection, ...

Is there a general biology that can ground astrobiological research? Explaining life’s “special powers” •In the closing line of On the Origin of Species, Darwin cryptically acknowledges that the process of natural selection is insufﬁcient to explain life’s core attributes. •Thus he begins the poetic last line with: • "There is grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one...." •Natural selection doesn’t explain the origin of the “special powers” that make life and evolution possible. •They are its necessary initial and supportive conditions. •Life’s special powers didn’t evolve from non-life, they emerged—a different process that evolution depends on. A ‘chicken and egg’ paradox • “If metabolism is dominated mostly by proteins, but is a prerequisite for the functioning of nucleic acid information molecules, how can a system like our current living cell, even the simplest prokaryote, with each of these two parts totally dependent upon the other, ever have evolved in the ﬁrst place?” — James Strick, 2003 Can a simple solution beat entropy?! • Since it occurred spontaneously the origin of life involved 1. a fairly simple molecular system producing 2. a highly improbable thermodynamic process that locally compensates for entropy increase 3. by organizing chemical work to continually repair locally accumulated thermodynamic damage/error The reverse engineering strategy

Tibor Ganti’s Chemoton (1971) Maximally reduced cell

i m

i = information, m = metabolism, c = cellular containment

Pursuing a “minimal cell” approach to the origin of life does not simplify far enough to explain its spontaneous origin. As a result it leaves unexplained the origin of a vast number of distinct types of molecules and their coincidental synergistic interrelationships. Protocells or frankencells? Simulating original life-forms by recombining components extracted from once-living cells to see if they “reanimate”

Can we assume that the ﬁrst steps toward life involved the same sorts of molecules currently comprising living cells? Doesn’t this sneak in the products of 3.5 billion years of evolution? Logical requirement approaches

E. Schrödinger: A self- reproducing automaton? negentropy + reproduces itself including this capacity! information Self-! S. Kauffman: Universal! description! construction! replication + mechanism! Assembly! work cycle instructions! T. Ganti: A! S! (Energy for! S! information + construction)! U! M! (Raw materials)! E! metabolism + D! container after John von Neumann Dawkins, Woese: J. von Neumann: self-description + naked replicator assembly instructions + assembler (molecule as both A-Life & cellular automata: pattern template & catalyst) replication with selection Autocatalysis: molecular self-organization • To be alive an organism doesn’t have to reproduce another organism, but it must continually reproduce those aspects of its material and formal constitution that are continually degraded by the very thermodynamic processes that make its existence possible. • This requires continual chemical work. • Differential replication of molecules can only contribute to the processes of living and evolving if this also includes the linked replication of the system that performs the chemical work required to accomplish molecular replication. • The reciprocal catalysis of an autocatalytic set of molecules accomplishes this via circular catalytic closure Reciprocal catalysis (autocatalytic set)

Lysis of molecule a Reciprocal catalysis occurs when into molecules b and one catalytic reaction produces a c by catalyst e product that catalyzes a second releases the energy reaction which produces a of the broken product that catalyzes the ﬁrst covalent bonds (and may involve multiple steps) Hypercycles: synergies between autocatalytic components

Although hypercycles increase the replication rate of their member molecules they are intrinsically unstable with respect to resources (weakest link problem), mutation, and openness to variants. Variants that differentially increase rates of the E>A reaction can degrade the whole cycle by changing the parameters of the A>B reaction (B). And variants of A that also catalyze D can short circuit the whole cycle (C). So there is no source of systemic integrity to prevent degradation of the synergy of catalytic closure. Self-organized dynamics can multiply

Hypercyclic interactions can self-organize

4 part autocatalytic hypercycle comprised of Networks of autocatalytic sets exhibit two reciprocally catalyzing peptides which differential growth of subsets due to outcompetes any one autocatalytic set for numbers of linked catalytic interactions substrates. (Lee et al. 1997) between sets. (Hordijk et al. 2014) Kant: the self-forming power of organisms vs mechanism

“... a machine has solely motive power, whereas an organized being possesses inherent formative power, and such, moreover, as it can impart to material devoid of it — material which it organizes. This, therefore, is a self-propagating formative power ...” “... in which, every part is reciprocally both end and means.” — Immanuel Kant, 1790 His conclusion: Reciprocal co-production resembles teleology but there is nothing for the sake of which it’s an end; i.e. function is in the eye of the beholder. Autopoiesis (= “self-fabrication”)

— Francisco Varela

Autopoiesis describes waste what must be true of an molecular metabolic organism without components reaction network explaining how it can be produces accomplished. generates determines Like Kant’s account it resources lacks an account of what self- maintains its systemic bounded system integrity and unity. 25% Only in the mind of the beholder • The property we recognize as autocatalytic synergy in these cases is not an intrinsic property of these molecules but is only a feature attributed to them by an observer reﬂecting on their interrelations. • These molecular components are each independent structures and not intrinsically linked to one another but are free to diffuse away from one another without interaction. • Their reciprocity and synergy only exist as a categorical judgment in the mind of the beholder. • So their reciprocal synergy is not produced, reproduced, or in any way persistent because it has no ontological status except as a mental category, as Kant recognized over 200 years ago. Morphodynamics (“self-organization”) Rayliegh-Benárd convection cell formation in a dish with a thin layer of constantly heated oil. [a d]

pattern of fluid movement creating a convection cell Note: It takes time for a morphodynamic attractor to form under the influence of constant extrinsic disturbance. Maximum entropy production (MEP) Self-organizing processes develop in persistent far-from- Rayliegh- equilibrium conditions . Benárd convection Persistent perturbation induces amplification and propagation of constraints that align dynamics Vortex with minimal total dissipation- formation path length. in fluids Thus minimizing work and maximizing entropy production. Self-organized processes are special converging types of non- Snow linear dynamical processes crystal which can become unstable and growth chaotic if conditions change. Self-organization versus Life Physical systems self-organize because this more efficiently eliminates the conditions that enable them, i.e. organized to be more efficiently self-eliminating. For this reason self-organization (morphodynamics) cannot provide an adequate explanation for the dynamics of life, which must be specifically organized to prevent spontaneous self-destruction and maintain extrinsic support. Paradox: Living systems must depend on morphodynamic processes to generate the constraints required to channel the work that maintains the order that constitutes system unity, and yet must prevent these processes from undermining the very conditions they depend on for their persistence. Organisms rely on self-organization for constraint generation yet invert its logic Organisms perform work to generate and maintain critical constraints against thermodynamic decay. Organisms depend on and utilize energetic and/or material gradients in their environment in order to perform work to reconstitute the constraints supporting their far-from-equilibrium dynamics. Organisms respond to counter or compensate for the loss of critical gradients necessary to maintain their synergistic integrity. Organisms evolve to increase the indirectness of dissipation-path length in order to extract more work. The emergence of a higher order dynamics is required to explain life

1. Homeodynamics (thermodynamics) Spontaneous constraint dissipation, reduction of correlation, loss of symmetries, equilibration e 2. Morphodynamics (“self-organization”) Ampliﬁcation of system-internal constraints/regularities due to the persistent extrinsic reversal of spontaneous dissipation 3. Teleodynamics (life, evolution, semiosis) e Self-reproducing/maintaining constraints on the synergistic interdependent coupling of morphodynamics Add the morphodynamics of self-assembly

viral capsule lipid membrane microtubule formation

Self-assembly occurs when the complementary geometry of molecular surfaces facilitates spontaneous tesselation into sheets, viral capsule polyhedrons, tubes, etc. microtubules Morphodynamic processes that each produce the others’ boundary constraints 1. Reciprocal catalysis plus biproduct • Spontaneously self-amplifying catalytic chain-reaction with at least one energy-liberating reaction ∑ Produces high locally asymmetric concentrations of a small number of molecular species ∆ Requires limited diffusion of interdependent catalysts 2. Enclosure by self-assembly • Spontaneous molecular tesselation into a closed structure due to stereochemical matching ∆ Produces constraint on molecular diffusion ∑ Requires persistently high local concentrations of a single species of component molecule Autogenesis

When one of the molecular # @ products of a reciprocal catalyzed catalytic cycle@ tends to reactions self-assemble# into a closed structure, encapsulation of the ensemble of reciprocal G catalysts becomes likely.

G Gn

n tubular G polyhedral 1/2 Morphodynamic reciprocity creates an autogenic work cycle exergonic extrinsic Self-assembly container closure stops breach dynamics by containing maintains blocks catalysts component catalyst damage availability diffusion initiates self- substrates reconstitution

& energy Reciprocal catalysis endergonic Extrinsic boundary conditions are intrinsically generated by reciprocal constraint generation processes Intrinsic constraint generation Self-assembly { Extrinsic boundary conditions

Extrinsic boundary conditions {

Reciprocal catalysis Intrinsic constraint generation This reciprocity constitutes a higher-order formal constraint that can be preserved indeﬁnitely in different substrates Intrinsic constraint generation Self-assembly { formalExtrinsic boundary conditions synergy constraint

Extrinsic boundary conditions {

Reciprocal catalysis Intrinsic constraint generation 50% Ratcheting constraint production

Each of the two self-organizing processes are dissipative and subject to maximum entropy production Each is halted before the boundary conditions for each are exhausted Entropy production thus ceases and constraints are preserved before being dissipated. Entropy export is halted by the very process of entropy export, yet this constraint-preserving capacity is maintained. This synergy is what limits MEP and enables life. Life requires generation, preservation, and compounding of substrate-transferrable constraints. Autogenesis: is a stochastic molecular analogue to mechanical ratcheting

Honey bee stinger Catch and gear ratchet

Repeated autogenic cycles regenerate component molecular constraints and prevent the decay of the higher order synergy constraint that preserves self Teleodynamics creates “selves” Teleodynamics necessarily constitutes an individuated (i.e. closed and integrated) unit system because it is organized to reconstitute this same system-disposition if perturbed, whether from outside or from spontaneous internal thermodynamic decay. It is the maintenance of system integrity and synergy It is not vested in any particular component substrate or collection of substrates. It is substrate-transferrable. The disposition to initiate self-reconstituting dynamics with respect to extrinsic dissipative inﬂuences creates an unambiguous self/nonself distinction. Self is thus vested in a higher-order formal synergy constraint on constraint-generating processes. Autogenic evolution and error correction

Shell enclosure will not only capture reciprocal catalysts in the local vicinity but also other molecules. Those that incidentally share catalytic inter-reactivity with autogen molecules will tend to be incorporated and replicated creating variant lineages. Those that don’t contribute to autogenic preservation or impede it without being lethal will tend to get crowded out in successive reproductions. Adaptive autogenesis = information substrate

Above: An autogenic complex with a capsule surface structure that binds a relevant substrate molecule and thereby becomes more fragile to disruption of enclosure that is proportional to the number of bound substrates. This increases the probability of selective dissociation only in reproductively supportive conditions. = information “about” the relevant state of the environment. From autogenesis to proto-genetics Any complex aperiodic molecular structure (like DNA) can embody “information” in the sense of Shannon “entropy” (i.e. the potential to convey reference because of its capacity to assume a variety of configurations) but this structure has no intrinsic reference. How can a molecular structure come to embody information about the dynamic and structural integrity of the system of which it is a part? I.e. how can it come to be a representation of system organization that can be referenced in the process of repairing or reproducing its essential system integrity and synergistic unity? The following scenario offers a plausibility argument. Limits to autogenic complexity A combinatorial catastrophe: A fundamental problem for systems employing many interdependent molecular interactions is the proliferation of competing side reactions. As the number of molecular species that need to interact increases (e.g. in reciprocal catalysis or self-assembly), the number of possible cross-reactions increases geometrically. Only a small fraction of these will be supportive of autogenesis and the proliferation of alternative interaction possibilities will compete with supportive interactions — using up critical components and wasting free energy. The increase in possible side reactions will slow the reconstitution and decrease the probability of persistence. So simple autogenic systems have limited evolvability. The possible molecular interactions grow exponentially with increasing numbers

The increase x z in molecular a components possible f b molecular creates a interactions combinatorial catastrophe a-f catalysts v w c making e u-z substrates successful & products d autogenesis improbable u y Viable autogenic systems involve only a small fraction of the possible reactions x z

a non- destructive catalytic f b reaction

molecular trans- formation u & synthesis e v w c a-f catalysts d Autogenic u-z substrates reactions u y & products

How can deleterious side reactions be selectively inhibited? An energy / information coincidence?

ATP-ADP

Phosphate (+) serves as the major vehicle for energy transfer and storage in living cells. Phosphates can polymerize (++) and are conveyed throughout cells by three-part molecules (base- sugar-phosphate) such as Why are they the building ATP. blocks of RNA and DNA? From energy capture to ofﬂoading catalytic constraints to a polynucleotide template

A. Energy-capture-assisted catalysis via nucleotide side-product. B. Nucleotide polymerization and catalyst binding in inert phase. C-D. Template-biased catalyst release constraining catalytic cycle. ... produces sequence-specific selection The relative proximity and orientation of catalyst molecules on a polymer template will bias the reaction probabilities between them due to distance and sequential timing of release. Sequences that constrain catalyst interaction probabilities closer to the optimal interaction network will be preferentially retained because of higher reproduction and repair rates. The template molecule thereby offloads some fraction of the higher order dynamical synergy constraint onto a structure that is not directly incorporated into autogenic dynamics. Could this help explain the origin of genetics?. 75% A part representing the whole of which it is a part Thus a molecular structure that is enmeshed in a teleodynamic system can increase or decrease the probability of system self-reconstitution, thereby potentially affecting preservation of that system and the specific molecular template structure. Such a molecule can literally re-present the topology of the dynamical network of interactions that optimally re-produces and maintains itself and its system. It is a part representing the whole by indirectly embodying the boundary conditions for its persistence along with the teleodynamics it stabilizes. Information emerges from and depends on teleodynamics A full theory of information able to encompass concepts like function, adaptation, representation, purpose, and normativity requires grounding in the work performed by teleodynamic processes. Since teleodynamic processes emerge from contraposed morphodynamic processes, which in turn emerge from contraposed thermodynamic processes, ignoring this dynamical base blinds theory to the causal efficacy and physicality of information as well as its semiotic essence. Origin of abiotic polymers A critical problem for the spontaneous emergence of life is the difficulty of abiotic synthesis of large organic polymers. Large semi-labile polymers are critical to the chemical dynamics of life because of the importance of large three-dimensional surfaces for stereospecific chemical interactions. Although water is ubiquitous to life it is a significant impediment to abiotic polymer formation because polymerization of organic molecules involves dehydration reactions.

ﬁn Miller-Urey provides an unexpected hint

A few simple amino-acids were found dissolved in the water but how they could become polymerized Looking beyond earth-life chemistry “The visible cyanide chemistry on outer solar system bodies is a continuing reminder that hydrides of the elements oxygen, carbon and nitrogen could have been a ready source of prebiotic molecules on Earth, as Urey (1952) had originally suggested. In Miller-Urey experiments (Miller and Orgel, 1974; Miller, 1984) for example, it seems clear ... that most of the alpha-amino acids obtained from methane, ammonia and water were secondary products arising from HCN polymers. HCN formed from methane and ammonia by electric discharge reactions (Matthews and Moser, 1966) would polymerize and then become hydrolyzed to amino acids either during reﬂux in the reaction ﬂask, or later during the working-up procedure.” from Matthews, C. (1992) Dark matter in the solar system: Hydrogen cyanide polymers, in Origins of Life and Evolution of the Biosphere 21:421-434. Clifford Mathews’ hypothesis: H- C –N polymer formation Large HCN polymers form spontaneously in environments lacking liquid water but which are rich in C,H,O, & N hetero-polyamidines formed e.g. in outer solar spontaneously from hydrogen system environments. cyanide in anhydrous conditions However, when placed in liquid aqueous contexts, polyamidines undergo side-chain substitution producing become hetero-polypeptides polypeptide-like forms when exposed to water A possible interplanetary sequence? HCN polymers likely form in outer planetary atmospheres, methane oceans, and cometary material. If non-aqueous autogens could form in these extreme conditions, they could be transferred to Mars/Earth (via comets) reaching water environments where HCN-based polymeric autogens would resist rapid lysis, undergo NH to O substitution into peptides, incorporate dissolved Could there be martian autogens?

Since they are unlike life, what should we look for? Autogenic life would resemble crystalline structures at a sub-viral scale, with atypical molecular features. Above: Scanning EM of inclusions in a Martian-origin meteorite. Thought too small to be life, but ... A tentative meta-taxonomy Autaea

Morphota Semeota (Biota)

morphology energy information reproducers cycling replicating

e.g. autogenic morphology energy reproducers cycling

Meta-taxonomy of paralife/protolife forms morphology based on mode of reproduction and reproducers component synthesis. Biota = earthlife; a variant of information-based forms. Toward a universal biology 1. Reciprocal facilitation between diverse morphodynamic molecular processes can produce end-directed systems which exhibit the capacity to reproduce and evolve 2.Information-based life (Semiota) likely evolved from these more generic protolife forms 3. Autogenic forms are probably far more widespread than life in the cosmos because they are much less substrate-critical 4. Yet the particular chemistry of life may be similar throughout the universe owing to the predominance of HCN chemistry and the simpler conditions required for autogenesis References Deacon (2012) Incomplete Nature: How Mind Emerged from Matter. NewYork: W. W. Norton & Co. Hordijk, Vaidya & Lehman (2014) Serial transfer can aid the evolution of autocatalytic sets. Journal of Systems Chemistry 5:4 1-8. Lee, Severin, Yokobayashi & Ghadiri (1997) Emergence of symbiosis in peptide self-replication through a hypercyclic network. Nature 390 591-594. Matthews (1992) Dark matter in the solar system: Hydrogen cyanide polymers, in Origins of Life and Evolution of the Biosphere 21:421-434 Rasmussen, Chen, Deamer, Krakauer, Packard, Stadler & Bedeau (2004) From nonliving to living matter. Science 303 964.