Non-Equilibrium Thermodynamic Foundations of the Origin of Life

Round 1

Reviewer 1 Report

Without a doubt, thinking about the origin of life is exciting for humanity. We could not be sure we were asking the right question, but we asked it. If the question is correct or accepted as valid in science, physics, chemistry, and biology, have to answer. Remarkably, the author uses the fundamentals of thermodynamics to build a reference framework to think about what we call "organic life" and its possible origin. For a reader familiar with the thermodynamics of equilibrium states and the thermodynamics of irreversible processes, including the work done by Prigogine (symmetry-breaking fluctuations and self-organization), reading this review work may become understandable. However, for a non-expert in the scientific and technical community, this review can become highly complicated, even more so due to the absence of a minimum mathematical formalism. In thermodynamics, an equation is easier to read than a sentence. We recommend that the author include more illustrations, diagrams, or schematics when discussing some ideas. In addition to this, a glossary of terms would also be appreciated. We have the following questions for the author, and these should be answered and considered in the manuscript. 

Line 160-166: There is only a second law of thermodynamics. Many statements and different mathematical expressions describe the second law, depending on the nature of the system, the process, and the states. What is the statement of the second law that the author uses to affirm that the second law is not valid for life? Explain, clarify. 

Line 213-223: According to the first law of thermodynamics, energy can be "dissipated" as heat, and this is why the first law efficiency of heat engines involves heat and work. In a classical sense, the energy not used to work dissipates as heat. The second law establishes that heat dissipated decreases or increases the entropy. An important consideration is that this heat is reversibly dissipated between the system and surroundings. The second law also states that if we consider irreversible processes, a fraction of the available energy is "dissipated" via the rate of entropy production. We are not sure that a relationship can be established between the energy dissipated via the rate of entropy production and the energy dissipated via heat transfer. Please explain why the author considers that dissipative structures maximize dissipation. What dissipation? 

Line 248-251: Please explain how the coupling of different irreversible processes should be understood. What implications does it have for the system and its surrounding?. 

Line 372-379: Due to a non-linear relationship between forces and flows, the system can access multiple states, stable or unstable, evolving through a certain number of intermediate states. The final state is a stable one. What is the energy cost for the system in the intermediate states? How is the second-law dissipation that accompanies the system's final state evaluated? Why does the author state that the final state, the most stable, is the one that guarantees the maximum dissipation?

 Line 427-437: The author is discussing classic quantum dissipation? Please clarify the meaning of dissipation in this context.

Author Response

I thank the reviewer for their careful reading of the manuscript and for their very useful comments.

Reviewer 1; for a non-expert in the scientific and technical community, this review can become highly complicated, even more so due to the absence of a minimum mathematical formalism. In thermodynamics, an equation is easier to read than a sentence. We recommend that the author include more illustrations, diagrams, or schematics when discussing some ideas. In addition to this, a glossary of terms would also be appreciated. 

Since this article is indeed meant for the non-expert in thermodynamic theory I have taken the advice of the reviewer and have attempted to explain the ideas and concepts at a more simple level. I have  included equations to describe the basics of non-equilibrium thermodynamics as established by Prigogine. I also have included 8 new illustrations and explanatory figures.

A Glossary of Thermodynamic Terms, as requested by the reviewer, is included as an Appendix, and have defined other technical terms throughout the text more carefully where they appear in the text.

Reviewer 1; Line 160-166: There is only a second law of thermodynamics. Many statements and different mathematical expressions describe the second law, depending on the nature of the system, the process, and the states. What is the statement of the second law that the author uses to affirm that the second law is not valid for life? Explain, clarify. 

I have re-written the section discussing the second law applied to open systems more carefully (new paragraph 176-188) considering the production of entropy due to irreversible processes occurring within the system and the flow of entropy over the boundary of the system. Although the organism itself can decrease its entropy (thereby apparently violating the second law) the organism plus its environment must obey the second law and increase total global entropy.

Reviewer 1; Line 213-223: Please explain why the author considers that dissipative structures maximize dissipation. What dissipation? 

Dissipative structures don’t necessarily maximize dissipation, but they increase dissipation when they arise. The dissipation referred to is that of the external generalized thermodynamic force over the system (e.g. temperature gradient or photon potential). The simplest way to describe dissipation is; “the natural tendency of the conserved quantities of Nature; energy, momentum, angular momentum, charge, etc. to be distributed over an ever greater number of microscopic degrees of freedom”. I have included this description at the first appearance of “dissipation” in the main text (new line 100) and included it in the Glossary of Thermodynamic Terms at the end of the article before the References.

Reviewer 1; Line 248-251: Please explain how the coupling of different irreversible processes should be understood. What implications does it have for the system and its surrounding?

In the coupling of different irreversible processes, the “product” of one process could act as a generalized thermodynamic force for another irreversible process. For example, the irreversible process of the dissipation of photons in the pigments in the leaves of plants provides heat, leading to a temperature gradient between the leaf and the surrounding air. This temperature gradient then leads to the irreversible processes of heat conduction from leaf to air and to evapotranspiration from the leaf which becomes part of another irreversible process, the water cycle. The implications that this non-equilibrium coupling has to the system is to include it as a part into a much greater dissipative system, including possibly both biotic and abiotic processes (e.g. the biosphere). We have now defined the coupling of irreversible processes and its implications more carefully in the text beginning at line 280, and have also included a definition of this coupling in the Glossary of Thermodynamic Terms.

Reviewer 1; Line 372-379: Due to a non-linear relationship between forces and flows, the system can access multiple states, stable or unstable, evolving through a certain number of intermediate states. The final state is a stable one. What is the energy cost for the system in the intermediate states? How is the second-law dissipation that accompanies the system's final state evaluated? Why does the author state that the final state, the most stable, is the one that guarantees the maximum dissipation?

The energy for the intermediate states in non-equilibrium systems may be either higher or lower than previous or final states. For example, as the distribution shifts from mainly a concentration profile of HCN in water in the initial state, it has to pass through activation barriers to arrive at a new state (new concentration profile of intermediate molecules) which can be either higher or lower in the Gibb’s free energy. The final state (a concentration profile of dissipative pigments like Adenine) may also be either higher or lower in Gibb’s energy than the initial or intermediates states. However, as the system evolves from a concentration profile of mainly HCN in water, through intermediate concentration profiles, to the final one of photon dissipating pigments, the rate of photon dissipation generally increases in each step.

These final product molecules with conical intersections are more stable since although the incident photons excite these molecules in the same way they do the intermediate molecules, the lifetimes of the final product molecules are decreased since these are the molecules with large quantum efficiency for dexcitation directly into heat through a conical intersection, instead of into some new configuration (implying greater stability under this UVC light which is necessary for their structuring). The excited state lifetimes of these final product molecules are thus so short that further reactions simply do not have time to occur (molecules are most reactive in their electronic excited state). Since their lifetimes are very short, the molecules regress rapidly to the ground state and are ready to receive another photon, giving these final product molecules greater dissipative efficacy than the intermediates or original precursors. They are thus more stable in this non-equilibrium thermodynamic sense (less chance of suffering further chemical reconfiguration under the impressed UVC light), not in the equilibrium sense of having lower Gribb’s free energy. It is known, for example, that the natural nucleobases have conical intersections but they are not the lowest Gibb's free energy tautomers, and that these later do not have conical intersections. I have included the above as a new paragraph lines 463 to 476.

Reviewer 1; Line 427-437: The author is discussing classic quantum dissipation? Please clarify the meaning of dissipation in this context.  

Here, I was referring to the dissipation of the chemical potential (the partial derivative of the Gibb’s free energy with respect to the mole numbers at constant temperature, pressure, and mole numbers of the other chemical constituents) for chemical reactions in order to make the analogy with dissipation of the photochemical potential in the following paragraph.

Quantum efficiency refers to the probability of a given photon of a given wavelength causing a particular photochemical reaction.  I have included a definition of “quantum efficiency” in the Glossary of Thermodynamic Terms.

Reviewer 2 Report

Manuscript background information

The author investigates how the processes during the origin of life can be rationalized by non-equilibrium thermodynamics.

Points in favour

• The author’s work is a well written review report how processes during the foundations of live can be described by far from equilibrium thermodynamics.
• An almost entirely philosophical point, very well explained and summarized in this work is the vitality of life, which is much more than the molecular production problem. Not the description of certain details we find in Nature, but the question “why do all these wonders occur?” might be beyond human imagination. In case that the author has a different opinion, please provide us with more insights.

Points detracting

• It is stated in the abstract that the non-equilibrium foundations are described for the non-expert. However, this goal is only partly reached as e.g. the bio-physico-chemical processes described in Fig. 5 can only be partly, if at all understood by a layman.
• The author states: “Many non-specialists also incorrectly assume that the second law is applicable to all systems, life included.” But isn’t this statement perfectly true? Why should the 2^nd law be only valid for isolated systems? A modern formulation of the 2^nd law can be found in the textbook: D. Kondepudi: Introduction to modern thermodynamics, Wiley 2008: “Whether we consider isolated, closed or open systems,      d_iS ≥ 0. It is the statement of the Second Law in its most general form.”
• The captions in Fig.1 refers to a green curve: However, there is no green curve in this Figure!
• Figure 3. The author points to Fig. 3 (a). But this label is missing!

Statement

• This reviewer suggests to clearly "sell" this paper as a review report if possible as almost all figures are taken from older works of the author of this manuscript. The only figure that is not taken from older works of the author is one containing a well known example from textbooks.

Minor flaws and typos    

• Line 306:  Earth’s surface not Earht’s …
• Line 503: “nucleobases” not nucelobases.
• Line 544: dissipation.

Author Response

I thank the reviewer for their kind words and for their useful comments which have helped improve the manuscript.

On the suggestion of the reviewer, I have made corrections and significant changes to the text in order to improve the redaction and the understanding for the non-expert. I have simplified concepts, provided more analogies, and, in particular, have improved the description of the process of non-enzymatic replication given in the caption of figure 5 (now figure 12) which the reviewer refers to. I have included 8 new figures to clarify concepts and have included a Glossary of Thermodynamic Concepts, as suggested by reviewer 1, which can be found at the end, before the References.

I have rewritten the paragraphs related to the applicability of the second law for open systems (new lines 185 to 191), emphasizing that the law still applies to the whole system (system plus environment) and how the internal entropy production for irreversible processes is positive definite. I have now introduced simple equations following Prigogine’s analysis by defining the change in entropy of the system as due to internal irreversible processes and flow into, or out of, the environment, as suggested by the reviewer.

I have corrected the color labeling of figure 1.

This paper is indeed meant to be a review of a particular non-equilibrium description of dissipative structuring of the fundamental molecules of life at the origin of life.  The theme of the special issue to which it belongs is applications of non-equilibrium thermodynamics to fundamental problems from nature.  I now clearly mention in the Abstract that this is a review paper.

I have corrected the spelling errors that the reviewer identified as well as other errors encountered.

Round 2

Reviewer 1 Report