As I can not talk about the ideas embodied in the paper I will write about the formal aspects.
When the author shows the ideas of the speakers, it is not enough to include a final reference to the articles of the original author, but it would be useful for the reader that the author proposes a distilled of the references of the cited articles. Thereby, clearly referencing the ideas that he is collecting during the introduction.

In my opinion, the paper has not a clear structure. I can understand that the author is just put in together all the different sessions of the conference, but I expect a little bit more effort from an author, as to be considered as such. You have to talk a history about the origins of life and the conflicts and agreements of the different hypothesis and approaches. I can not see that in the paper.

The text is not clear, and sometimes it is hard to understand the sentences. But I am not a native speaker.

Author Response

This is a paper that recapitulates the talks that were delivered by NoR CEL’s network members during the 2018 meeting. as a result of this, it is a paper difficult to review because we cannot change what has already been said. The paper exposes a compendium of ideas about the origins of life, how this proto-organisms could evolve and some exobiotics alternatives. As the paper is a compendium of oral presentations, I do not understand why the paper is not signed by al the speakers that gave the ideas. As I can not talk about the ideas embodied in the paper I will write about the formal aspects. When the author shows the ideas of the speakers, it is not enough to include a final reference to the articles of the original author, but it would be useful for the reader that the author proposes a distilled of the references of the cited articles. Thereby, clearly referencing the ideas that he is collecting during the introduction. In my opinion, the paper has not a clear structure. I can understand that the author is just put in together all the different sessions of the conference, but I expect a little bit more effort from an author, as to be considered as such. You have to talk a history about the origins of life and the conflicts and agreements of the different hypothesis and approaches. I can not see that in the paper. The text is not clear, and sometimes it is hard to understand the sentences. But I am not a native speaker. This is a report from a conference which reports the work of the scientists presenting at the conference. It is not a review paper, therefore the reviewers comments do not apply ion this instance. Finally, this paper has been checked by a native English speaker, prior to submission, so I disagree with final comment, the reviewer should have cited examples of what he meant by not understood. It is unfortunate that the reviewer is non-native English speaker in this case.

Reviewer 2 Report

To organize the general presentation of the particular contributions, of course, it may be practical to point out two or three ‘front runners’ (Sect. 3) among the numerous models and hypotheses concerning the origins and earliest evolution of life on Earth (or elsewhere in the Cosmos). In a broader perspective (Sect. 8; “What’s Next?”), however, it becomes negligent not to take note of additional possibilities at all. As for potential extensions into future considerations – with reference to input from this conference report – four issues appear especially relevant, as seen from my personal judgement and priorities: (i) Kompanichenko’s general concept of “thermodynamic inversion” and its particular pertaining to “prebiotic chemistry under oscillating conditions”; (ii) Jheeta’s notion of “probable chemistry” – presumed to be “more probable than improbable” under particular early-Earth conditions, from which life may have emerged – if only this concept could be restated in terms of thermodynamic far-from-equilibrium dynamics; (iii) Grunska’s general concerns about the testability of scientific models of life, in the first place; and (iv) Jheeta’s somewhat ambivalent thoughts in concluding the meeting report that, “in trying to fully explain the chemical evolution of life, unfortunately we only have conjecture at this stage - this report highlights that very point, as all the scientists featured have outlined a theoretical frame-work, with very little concrete chemistry”.

To further motivate my concerns about these particular issues, I should like to draw attention to a number of additional suggestions in the literature, even though these are not (yet?) considered mainstream in this inherently conjectural field. More generally speaking, at this occasion, one could even make the provocative argument that stringent experimental testability criteria cannot realistically be applied to any particular chemical model of life’s putative emergence (for a fundamental critique of any ‘Privileged-Function First’ kind of OoL model, see [1]. Instead, the conjectural assembly of more or less plausible scenarios may be the best that science has to offer in researching this arguable field. The conceptual assembly of various conceivable scenarios should focus on integrational approaches, trying to narrow the obvious gap between the knowable structural/functional constraints on physical/chemical interactions in living systems today and reasonable inferences about presumptive Early-Earth conditions.
_{[1] Lanier, K. A., & Williams, L. D. (2017). The origin of life: models and data. J. Mol. Evol. 84, 85–92.}

Most models based on a ‘Privileged-Function’ – such as RNA-, lipid- or peptide-first hypotheses – attempt to carry just a single class of molecules as far as possible, not considering additional types for potential cooperation before it may be too late. In contrast, more realistic integrational approaches are beginning to focus on combining the most promising prebiotic candidates of different molecular composition as early as possible in a gradual complexification process towards life-like self-organization. The following examples deserve particular attention in this context.

Of relevance to Kompanichenko’s requirement of oscillating conditions (i), a bimodal terrestrial model [2] has been suggested to replace the submarine-vent scenarios favored before. The driving mechanism is based on environmentally oscillating wet/drying cycles in the vicinity of terrestrial hydrothermal pools or vents, resulting in two alternating conglomeration modes of potentially biogenic matter, as modulated by lipid-dominated dynamics: attaching to newly exposed surface as multilamellar films upon evaporation and, in turn, dispersing into vesicular ‘protocell’ suspension upon rehydration. While the authors themselves put large weight on rapid dispersion of ‘protocells’ in high numbers, I would rather de-emphasize the importance of prebiotic lipids early on put more weight on internal cohesion and preferential adhesion as surface-attached ‘proto-biofilms’ [3]. Suggested on similar grounds, ‘neighborhood selection’ – an analog of group selection without bounded groups – may have operated in attached layers of lipid-independent ‘surface protoplasm’ [4].
_{[2] Damer, B., & Deamer, D. (2015). Coupled phases and combinatorial selection in fluctuating hydrothermal pools: A scenario to guide experimental approaches to the origin of cellular life. Life, 5, 872–887.}
_{[3] Egel, R. (2014). Origins and emergent evolution of life: The colloid microsphere hypothesis revisited. Orig. Life Evol. Biosph., 44, 87–110.}
_{[4] Baum, D. A. (2015). Selection and the origin of cells. Bioscience, 65, 678–684.}

Of relevance to Jheeta’s ‘probable chemistry’ (ii) – especially to the emphasis given to aa~tRNA–mRNA interactions in ribosomes – it is worth noting that tRNA–peptide interactions for amino-acyl activation may arguably be of even earlier evolutionary significance, in forming the very basis for early emergence for an intimate ‘peptide/RNA partnership’ [5]. In this scenario, the first role of primitive aa~tRNAs may be have been in non-ribosomal synthesis of more or less ‘stochastic’ peptides [6].
_{[5] Carter, C. (2015). What RNA world? Why a peptide/RNA partnership merits renewed experimental attention. Life, 5, 294–320.}
_{[6] Caetano-Anollés, G., Kim, K. M., & Caetano-Anollés, D. (2012). The phylogenomic roots of modern biochemistry: origins of proteins, cofactors and protein biosynthesis. J. Mol. Evol., 74, 1–34.}

As for Grunska’s contribution about scientific models of life (iii), it may be timely now to look for ‘A World beyond Chemistry’ – alluding to Stuart Kauffman’s most recent book, “A WORLD BEYOND PHYSICS” [7]. In there, the author posits three nested ‘closures’ to characterize life – the living phase state – as a scientically agreeable form of “nonmystical holism” [7, p. 30], combining the partly independent features of catalytic closure [8], work task closure [9] and constraint closure [10] into a common, irreducible whole. It may seem difficult to condense the gist of these abstract concepts into a summarizing paragraph, but I’ll give it a try.
_{[7] Kauffman, S. A. (2019). A World Beyond Physics: The Emergence and Evolution of Life. Oxford University Press.}
_{[8] Kauffman, S. A. (1993). The Origin of Order: Self Organization and Selection in Evolution. Oxford University Press.}
_{[9] Kauffman, S. A. (2000). Investigations. Oxford University Press.}
_{[10] Montévil, M., & Mossio, M. (2015). Biological organisation as closure of constraints. J. Theor. Biol., 372, 179–191.}

As Kauffman put it, “The order [of life] is historically contingent, yet not fully random” [7, p. 6]. For modeling the putative beginning of this contingent order – from the ‘probable chemistry’ that presumably prevailed on the prebiotic early Earth – it would be essential to subsume all three closure transitions in a unified scenario. The closure term in general applies to networking topologies at three different levels: catalytic, constraint, and work task. Catalytic closure means that networks of closed reaction cycles are selectively established and maintained, which requires external input of utilizable energy. Importantly, all the reactants, reactions and eventual catalysts (if needed) must be available as environmental ‘foodstuff’ or be produced by the network itself. Constraint closure implies that all the means of directional channeling , as regards energy transfer and material flows, are being produced by the network as well; such means act as ‘constraints’ in preventing part of the absorbed energy from being degraded to random movement as
unusable heat. In the jargon of physics, the retained part of energy is doing some ‘work’, be it by acceleration of inert mass in mechanical machines or in the storage of ‘high-energy’ chemical bonds, as present in accumulating bio-matter. Yet, more than this, the living state is not only providing for all the reactional constraints; it also defines the momentary goals – the work tasks – for harvesting the energy required and doing the suitable work. The various work tasks, too, are organized sequentially in cyclic repetition, referred to as work task closure. Yet, being a physical/chemical system – with no mystical foresight into the unknowable future – these closures can only have emerged by numerous stochastic trials and gradual optimization, relentlessly exploring the combinatorial space of momentary opportunities – the “Adjacent Possible” [11]. The momentary opportunities have changed dramatically over geological time, and evolving life itself is significantly contributing to these changes.
_{[11] Kauffman, S. (2003). Molecular autonomous agents. Phil. Trans. R. Soc. Lond. A, 361, 1089–1099.}

Notably, all these additional quotations are based on “conjecture and theoretical frame-work, with very little concrete chemistry”. Jheeta’s yearning reflections in this regard (iv), therefore, might as well be given a more positive twist. Inasmuch as traditional ‘school bench’ chemistry is generally keeping away from the ‘dirty’ setups of hard-to-control one-pot experiments, this branch is about to run into natural limits when it comes to serious testing of realistic OoL hypotheses. This is in obvious contrast to the potential impact of the NoR-CEL network, as presented here in Jheeta’s meeting report, since the development of technical means for computer-assisted simulation of shifting kinetics and dynamics in multicomponent interactions is still on the rise. Scientists specialized in ‘conjecture and theoretical frame-work’ should take pride in taking the lead in cooperative OoL research. Not being conceptually limited to over-simplistic models on ‘privileged functions’, therefore, the main efforts of computer-assisted simulation studies in the future should be concentrated on more creative multicomponent scenarios than the current ‘front runner’ models that hitherto have failed to live up to the high expectations connected to their original proposition and still persistent popularity. I can only hope for that future meetings of the NoR-CEL network will bear substantial witness to such a shift of emphasis.

Comments for author File: Comments.pdf

Author Response

Doctor Sohan Jheeta’s paper “Molecules to Microbes” comprises a Conference Report about the fourth NoR-CEL network meeting in 2018. It can thus be considered a bounded task – distinctly different from ordinary articles. In my critical comments, therefore, I’ll mainly concentrate on the author’s more general remarks across the manuscript. Besides, I fully agree with the NoR-CEL objectives – “to collate and communicate the vastly multidisciplinary aspects of the origin of life”. As for my background, throughout my academic career I was not involved in studies pertaining to the Origin of Life (OoL) directly, but only later I became curious about the theoretical foundations of complex life‘s conceivable beginnings – after formal retirement from experimental research in molecular eukaryote life-cycle genetics. To organize the general presentation of the particular contributions, of course, it may be practical to point out two or three ‘front runners’ (Sect. 3) among the numerous models and hypotheses concerning the origins and earliest evolution of life on Earth (or elsewhere in the Cosmos). In a broader perspective (Sect. 8; “What’s Next?”), however, it becomes negligent not to take note of additional possibilities at all. As for potential extensions into future considerations – with reference to input from this conference report – four issues appear especially relevant, as seen from my personal judgement and priorities: (i) Kompanichenko’s general concept of “thermodynamic inversion” and its particular pertaining to “prebiotic chemistry under oscillating conditions”; (ii) Jheeta’s notion of “probable chemistry” – presumed to be “more probable than improbable” under particular early-Earth conditions, from which life may have emerged – if only this concept could be restated in terms of thermodynamic far-from-equilibrium dynamics; (iii) Grunska’s general concerns about the testability of scientific models of life, in the first place; and (iv) Jheeta’s somewhat ambivalent thoughts in concluding the meeting report that, “in trying to fully explain the chemical evolution of life, unfortunately we only have conjecture at this stage - this report highlights that very point, as all the scientists featured have outlined a theoretical frame-work, with very little concrete chemistry”. To further motivate my concerns about these particular issues, I should like to draw attention to a number of additional suggestions in the literature, even though these are not (yet?) considered mainstream in this inherently conjectural field. More generally speaking, at this occasion, one could even make the provocative argument that stringent experimental testability criteria cannot realistically be applied to any particular chemical model of life’s putative emergence (for a fundamental critique of any ‘Privileged-Function First’ kind of OoL model, see [1]. Instead, the conjectural assembly of more or less plausible scenarios may be the best that science has to offer in researching this arguable field. The conceptual assembly of various conceivable scenarios should focus on integrational approaches, trying to narrow the obvious gap between the knowable structural/functional constraints on physical/chemical interactions in living systems today and reasonable inferences about presumptive Early-Earth conditions. [1] Lanier, K. A., & Williams, L. D. (2017). The origin of life: models and data. J. Mol. Evol. 84, 85–92. Most models based on a ‘Privileged-Function’ – such as RNA-, lipid- or peptide-first hypotheses – attempt to carry just a single class of molecules as far as possible, not considering additional types for potential cooperation before it may be too late. In contrast, more realistic integrational approaches are beginning to focus on combining the most promising prebiotic candidates of different molecular composition as early as possible in a gradual complexification process towards life-like self-organization. The following examples deserve particular attention in this context. Of relevance to Kompanichenko’s requirement of oscillating conditions (i), a bimodal terrestrial model [2] has been suggested to replace the submarine-vent scenarios favored before. The driving mechanism is based on environmentally oscillating wet/drying cycles in the vicinity of terrestrial hydrothermal pools or vents, resulting in two alternating conglomeration modes of potentially biogenic matter, as modulated by lipid-dominated dynamics: attaching to newly exposed surface as multilamellar films upon evaporation and, in turn, dispersing into vesicular ‘protocell’ suspension upon rehydration. While the authors themselves put large weight on rapid dispersion of ‘protocells’ in high numbers, I would rather de-emphasize the importance of prebiotic lipids early on put more weight on internal cohesion and preferential adhesion as surface-attached ‘proto-biofilms’ [3]. Suggested on similar grounds, ‘neighborhood selection’ – an analog of group selection without bounded groups – may have operated in attached layers of lipid-independent ‘surface protoplasm’ [4]. [2] Damer, B., & Deamer, D. (2015). Coupled phases and combinatorial selection in fluctuating hydrothermal pools: A scenario to guide experimental approaches to the origin of cellular life. Life, 5, 872–887. [3] Egel, R. (2014). Origins and emergent evolution of life: The colloid microsphere hypothesis revisited. Orig. Life Evol. Biosph., 44, 87–110. [4] Baum, D. A. (2015). Selection and the origin of cells. Bioscience, 65, 678–684. Of relevance to Jheeta’s ‘probable chemistry’ (ii) – especially to the emphasis given to aa~tRNA–mRNA interactions in ribosomes – it is worth noting that tRNA–peptide interactions for amino-acyl activation may arguably be of even earlier evolutionary significance, in forming the very basis for early emergence for an intimate ‘peptide/RNA partnership’ [5]. In this scenario, the first role of primitive aa~tRNAs may be have been in non-ribosomal synthesis of more or less ‘stochastic’ peptides [6]. [5] Carter, C. (2015). What RNA world? Why a peptide/RNA partnership merits renewed experimental attention. Life, 5, 294–320. [6] Caetano-Anollés, G., Kim, K. M., & Caetano-Anollés, D. (2012). The phylogenomic roots of modern biochemistry: origins of proteins, cofactors and protein biosynthesis. J. Mol. Evol., 74, 1–34. As for Grunska’s contribution about scientific models of life (iii), it may be timely now to look for ‘A World beyond Chemistry’ – alluding to Stuart Kauffman’s most recent book, “A WORLD BEYOND PHYSICS” [7]. In there, the author posits three nested ‘closures’ to characterize life – the living phase state – as a scientically agreeable form of “nonmystical holism” [7, p. 30], combining the partly independent features of catalytic closure [8], work task closure [9] and constraint closure [10] into a common, irreducible whole. It may seem difficult to condense the gist of these abstract concepts into a summarizing paragraph, but I’ll give it a try. [7] Kauffman, S. A. (2019). A World Beyond Physics: The Emergence and Evolution of Life. Oxford University Press. [8] Kauffman, S. A. (1993). The Origin of Order: Self Organization and Selection in Evolution. Oxford University Press. [9] Kauffman, S. A. (2000). Investigations. Oxford University Press. [10] Montévil, M., & Mossio, M. (2015). Biological organisation as closure of constraints. J. Theor. Biol., 372, 179–191. As Kauffman put it, “The order [of life] is historically contingent, yet not fully random” [7, p. 6]. For modeling the putative beginning of this contingent order – from the ‘probable chemistry’ that presumably prevailed on the prebiotic early Earth – it would be essential to subsume all three closure transitions in a unified scenario. The closure term in general applies to networking topologies at three different levels: catalytic, constraint, and work task. Catalytic closure means that networks of closed reaction cycles are selectively established and maintained, which requires external input of utilizable energy. Importantly, all the reactants, reactions and eventual catalysts (if needed) must be available as environmental ‘foodstuff’ or be produced by the network itself. Constraint closure implies that all the means of directional channeling , as regards energy transfer and material flows, are being produced by the network as well; such means act as ‘constraints’ in preventing part of the absorbed energy from being degraded to random movement as unusable heat. In the jargon of physics, the retained part of energy is doing some ‘work’, be it by acceleration of inert mass in mechanical machines or in the storage of ‘high-energy’ chemical bonds, as present in accumulating bio-matter. Yet, more than this, the living state is not only providing for all the reactional constraints; it also defines the momentary goals – the work tasks – for harvesting the energy required and doing the suitable work. The various work tasks, too, are organized sequentially in cyclic repetition, referred to as work task closure. Yet, being a physical/chemical system – with no mystical foresight into the unknowable future – these closures can only have emerged by numerous stochastic trials and gradual optimization, relentlessly exploring the combinatorial space of momentary opportunities – the “Adjacent Possible” [11]. The momentary opportunities have changed dramatically over geological time, and evolving life itself is significantly contributing to these changes. [11] Kauffman, S. (2003). Molecular autonomous agents. Phil. Trans. R. Soc. Lond. A, 361, 1089–1099. Notably, all these additional quotations are based on “conjecture and theoretical frame-work, with very little concrete chemistry”. Jheeta’s yearning reflections in this regard (iv), therefore, might as well be given a more positive twist. Inasmuch as traditional ‘school bench’ chemistry is generally keeping away from the ‘dirty’ setups of hard-to-control one-pot experiments, this branch is about to run into natural limits when it comes to serious testing of realistic OoL hypotheses. This is in obvious contrast to the potential impact of the NoR-CEL network, as presented here in Jheeta’s meeting report, since the development of technical means for computer-assisted simulation of shifting kinetics and dynamics in multicomponent interactions is still on the rise. Scientists specialized in ‘conjecture and theoretical frame-work’ should take pride in taking the lead in cooperative OoL research. Not being conceptually limited to over-simplistic models on ‘privileged functions’, therefore, the main efforts of computer-assisted simulation studies in the future should be concentrated on more creative multicomponent scenarios than the current ‘front runner’ models that hitherto have failed to live up to the high expectations connected to their original proposition and still persistent popularity. I can only hope for that future meetings of the NoR-CEL network will bear substantial witness to such a shift of emphasis. The reviewer does not add any amendments - these are his observations and he approved the paper for submission. This was a review paper only whereas the comments may be interesting, one would need to do at least a book in order to address all his points.

Article Menu

Molecules to Microbes

Article Versions

Further Information

Guidelines

MDPI Initiatives

Follow MDPI