Chemical Organization Theory as a General Modeling Framework for Self-Sustaining Systems

Round 1

Reviewer 1 Report

This paper describes using Chemical Organization Theory (COT) as an alternative model for modeling a wide range of complex systems. It is clear and well written. While I am not totally convinced this model enables new approaches that are not available using other models, I believe this paper should be published. At the very least, the COT model is a refreshing, welcome approach that encourages new multi-disciplinary research.

What is missing from this paper are more references to chemistry, specifically the use of mass action kinetics and stoichiometry, as well as the field of Systems Chemistry, that have been employed towards solving these same problems. For more references on Systems Chemistry, see, for example: Ashkenasy et al, Chemical Society Reviews 46, 9 (2017); von Kiedrowksi et al, J. Systems Chemistry 1, 1 (2010); Wagner et al, Life 9, 45 (2019).

Author Response

We have added references to Systems Chemistry and to Mass Action Kinetics as suggested

Reviewer 2 Report

This is a strong reject. In essence, the authors claim that ("such a philosophy assumes that reality..') that the natural sciences are not sufficient for modelling the world. It is of course admissible to search for grounding organizational principles, but that is the domain of science and not of philosophy.

The paper makes a few generic remarks about classical reaction networks. These remarks are not necessarily wrong, but of no avail. There is nothing new here. At no point are numerical simulations presented, demonstrating that the proposed 'new interpretation' of standard reaction networks would lead to new results.

Author Response

It is not clear to us how the reviewer has so thoroughly misunderstood our paper. We never said that the natural sciences are not sufficient for modeling the world: on the contrary, the whole point of the paper is to extend the domain that can be modeled by proposing a novel formalism. We did not present numerical simulations because these have already been extensively presented in other papers that we refer to, both by our groups and others. The point of this paper is precisely to provide a general, theoretical introduction without going into the quantitative results.

Reviewer 3 Report

This article provides an overview of chemical organization theory (COT), a framework designed to represent (and possibly dynamically simulate) complex systems composed of many mutually interacting parts. COT includes resources and reactions as fundamental components: reactions describe the processes by which one set of resources transforms into another set. Within these systems, stable dynamic patterns can be formed, called "organizations", which can act as attractors of the dynamics of the system: they are closed and self-sustaining, and consequently allow the modeling of autopoiesis, in which the organization reproduces its components continuously. The COT theory finds applications in various fields.

The work is professional and well written, it clearly establishes its main points and the background is well presented. The topics are relevant to the journal.

Being a review, the paper does not present new concepts or a radically new type of algorithm. Rather, it constitutes an interesting re-proposal of topics already presented individually, fully exploring their potential, highlighting their advantages and proposing interesting points of view. The authors deliberately leave out the quantitative aspects of the theory, to highlight its ability to represent a large set of different types of systems. It is an interesting approach, which in fact in some situations allows a simple but effective approach to the identification of complex dynamic organizations. The omission of the quantitative aspects was also made to highlight (and if possible increase) the degree of generality of the analyzes made possible by the theory, making them as independent as possible from the details of the dynamics.

However, this is also the main limitation of the paper: ignoring the quantitative aspects sometimes makes it impossible to identify truly stable or self-sustaining organizations - and in fact on occasion the authors are forced to introduce quantitative explanations (the complete COT theory also provides interesting quantitative aspects, which obviously may depend on the particular problem examined).

That said, the paper remains a stimulating and comprehensive presentation of an interesting theory and depicts notable applications, and therefore deserves to be published. Below I present some points that I think still need to be improved before publication.

·       The authors write: “The general character means that COT can describe systems and processes in any discipline - from elementary…”.  As we will see, a purely qualitative application of the COT theory has some weaknesses. I would therefore propose to de-emphasize the sentence, replacing the word "any" with the word "many"

·       The reactions described in lines 400-404 expel heat into the environment, without having produced it. It is true that the authors in section 5 state that "This also helps us to simplify our models by ignoring ever-present inputs (such as air or sunlight) or outputs (such as dissipated heat or waste)" (lines 548-549 ), but here we are in section 3. The authors should add heat in the reactions, or they should anticipate the comment made in section 5 here.

·       The authors write: “Some of the resources present in that set will be consumed by the reactions, but not produced, or at least not produced in sufficient amounts to replace the amounts consumed” (lines 465-466). With the comment “at least not produced in sufficient amounts to replace the amounts consumed" the authors state that it is necessary to quantitatively analyze the organization to allow a correct observation of the self-maintenance capacity. The purely qualitative observation, although very useful in the initial identification of the resources and reactions involved in the organization, is therefore not sufficient to determine the degree of self-sufficiency of the organization itself. It's an observation that might be obvious, but the overall tone of the paper goes in the opposite direction. The authors could add an observation or a comment, here or in the initial part of the paper.

·       The authors write: “A reduction in the number of predators will then let the rabbit population recover. Such a dynamics follows naturally from our earlier observation that reaction rates normally increase together with the concentration of their reactants” (lines 612-614). Again, quantities are necessary for the correct understanding of the system. Furthermore, here we also mention some dynamic rules, dependent on the concentrations of the reactants (a reminiscence of the "chemical" origin of the COT theory).

·       The authors write: “One way to achieve this in COT is to label resources with indices that indicate the specific cell in which the resource is located [12], while adding the constraint that resources can only react with resources that reside in the same cell (i.e. that have the same label). Topological structure can then be introduced…” The entities of the COT theory allow this system to be represented, yes. At least in this case the new representation does not seem to add anything compared to the "traditional" descriptions of the system if it does not even represent a more complicated version. The authors could therefore continue to state that the COT representation can also be used in this case (thereby underlining its versatility), but they could also comment that the application of this representation does not always constitute a simplification of the possible approaches to the problem.

·       The authors write: “is possible to build reaction networks where reactions play the role of complex logical gates…” (line 817). How the theory can handle resource variation over time, a variation that depends on (i) reaction times and (ii) on the number of reactions that separate input and output? Is it necessary to wait for the system to reach equilibrium? In any case, here too it seems to me that quantity management (and therefore a dynamic simulation) is useful if not necessary.

·       The authors write: “That means that it exhibits not just the most basic features of life, but of cognition [13,25], intelligence, and intentionality.” (line 876) As before: it is possible to represent situations, but the COT theory does not always represent an advantage over whatever representation is already used.

·       The authors write: “COT models are easy to analyze computationally: entering a set of reactions into an appropriate computer program will allow you to quickly discover the different possible outcomes together with the conditions under which they can arise” (lines 949-951). If we consider only structure to be important, this is true. Sometimes, however, it is also necessary to carry out dynamic simulations (in this case, the authors could remember that the "dynamic" part of the COT theory also exists).

·       The authors write: “While the qualitative model can be seen as a mere ‘abstraction’ of the full quantitative dynamics [35], its algebraic properties are so strong that many non-trivial properties can be established at this level without need to determine quantitative dependencies or concentrations.” I think that the authors have shown that this is true in many interesting cases. I therefore have no remarks to make, other than perhaps to suggest de-emphasizing their initial approach (as already commented), in which they state that "The general character means that COT can describe systems and processes in ***any*** discipline"

Best regards

Author Response

We thank the reviewer for a thorough and balanced appraisal of our work. We have amended it as suggested by noting that the formalism rather than being applicable to "all disciplines" is applicable to "the most diverse disciplines". We have also added heat to the reactions in the Earth model, as suggested, because that indeed makes the model more coherent.

We appreciate the reviewer's observation that a qualitative version of the formalism is limited in its applicability. We never suggested that the qualitative version is sufficient for detailed modelling, only that the qualitative version provides a surprisingly powerful means of establishing a first understanding of a complex problem domain, which can then be further refined, eventually resulting in a quantitative simulation of the dynamics. In the revision, we have more explicitly noted (lines 319-322) that a full model needs a dynamic rule, which in chemistry is traditionally provided by mass action kinetics, but which can take many other forms as well. It is precisely because of the many different forms that a dynamics can take that this paper has remained at the qualitative level, so as to give a broad overview of the capabilities of COT...