Authors:
(1) STUART KAUFFMAN;
(2) ANDREA ROL.
Table of Links
Part II. The first Miracle: The emergence of life is an expected phase transition – TAP and RAF.
Part IV. New Observations and Experiments: Is There Life in the Cosmos?
Conclusion and Acknowledgments
Part I. A Definition of Life
We have no agreed-upon definition of life. We here build toward the following: Life is a non-equilibrium, self-reproducing chemical reaction system that achieves: i. Collective autocatalysis, ii. Constraint Closure, iii. Spatial Closure; iv. as such, living entities are Kantian Wholes. We explain these concepts below.
Collectively Autocatalytic Sets
A collectively autocatalytic set, CAS, is an open chemical reaction system fed with exogenous molecular and energetic building blocks, having the property that a last chemical reaction step forming each molecule in the set is catalyzed by at least one molecule in the set or by one molecule in the food set. Figure 1a shows a simple example, (2). Figure 1b shows a more complex example (3).
The concept that life must be based on template replicating polynucleotides has dominated the origin of life field for some 50 years, (4,5). Yet replication of a “nude replicating RNA gene” has not yet been achieved, (6). Nevertheless, this goal may be achieved.
The familiar concept of a template replication double stranded RNA sequence is a specific example of a collectively autocatalytic set. Each strand is a template catalyst for the synthesis of the other strand. However, the concept of collective autocatalysis is far broader.
In sharp contrast to the hopes for a replicating RNA sequence, collectively autocatalytic sets of DNA, of RNA, and of peptides have been constructed. The first, a DNA collectively autocatalytic set, was constructed by G. von Kiedrowski, (7). An RNA collectively autocatalytic set was achieved by N. Lehman and colleagues, (8). This set spontaneously self organizes given its building blocks. A collectively autocatalytic set of nine peptides constructed by G. Ashkenasy, (9), is shown in Figure 2. Autocatalytic sets of lipids have also been considered, (10).
These results are of fundamental importance. Creating self-reproducing open chemical reaction systems is achieved.
Stunning evidence now demonstrates the presence of small molecule collectively autocatalytic sets containing no DNA, RNA, or peptide polymers, in all 6700 prokaryotes, Figure 3, (11,12). These small molecule self-reproducing sets contain from hundreds to several thousand small molecules and reactions among them. These autocatalytic sets synthesize several amino acids and ATP. The sets are identified computationally. It remains to be shown that they reproduce in vitro.
The presence of small molecule collectively autocatalytic sets in all 6700 prokaryotes strongly suggests that the first chemical systems capable of self-reproduction in the universe were precisely such sets. We show below that the emergence of such sets is expected.
The identification of small molecule autocatalytic sets bears on the ongoing debate concerning the necessity for template replicating polynucleotides in the origin of life. Such a “nude RNA gene” would have to evolve RNA sequences to catalyze a connected metabolism to create and sustain its own building blocks. However, there is no reason at all why such a connected metabolism by itself would also be collectively autocatalytic. This consideration increases the confidence that the origin of molecular reproduction was through the emergence of small molecule collectively autocatalytic sets.
Life: Kantian Wholes, Catalytic Closure, Constraint Closure, Spatial Closure
Kantian Wholes
In the 1790s, philosopher Immanuel Kant introduced a fundamental concept: An organized being has the property that the Parts exist for and by means of the Whole, (13). Kant’s insight has lain dormant for 230 years. All living beings are Kantian Wholes that exist for and by means of their Parts. You are a Kantian Whole. You exist by means of your Parts – heart, liver, kidneys, lungs, brain. Your Parts exist by means of you, the Whole. You reproduce, and your children inherit your Parts.
All living organisms are Kantian Wholes. This includes the doubted class of viruses. Inside the environment of the cell, viruses are Kantian Wholes that reproduce. The Parts of the virus, in the context of the cell, create multiple copies of the Parts of the virus that self-assemble into the mature virus Whole. It is of interest that a definition of life including that of a Kantian Whole classifies viruses as alive.
Kantian Wholes are a special class of dynamical physical systems. A crystal is not a Kantian whole. The atoms of the crystal can exist without being parts of the crystal. A brick is not a Kantian Whole. A cell is a Kantian Whole.
Catalytic Closure
A collectively autocatalytic set, such as the 9-peptide set in Figure 2, achieves Catalytic Closure. Each reaction in the system is catalyzed by at least one molecule in the system. All living cells achieve catalytic closure. No molecule in a living cell catalyzes its own formation. The set molecules in a living cell, a Whole, achieves catalytic closure as the cell reproduces, (14,15,16).
Systems that achieve catalytic closure are also Kantian Wholes. Each of the peptides in the 9-peptide collectively autocatalytic set in Figure 2 is a Part that exists for and by means of the Whole set of nine peptides whose mutual catalysis enables all the Parts to exist.
Constraint Closure
Living cells, including a small molecule collectively autocatalytic set of the type found in all 6700 prokaryotes, achieve a newly recognized and profound property: Constraint Closure, (17). Thermodynamic work is the constrained release of energy into a few degrees of freedom, (18). An example is a cannon with powder at its base and a cannon ball nestled next to the powder. When the power explodes, the cannon, that is both a boundary condition and a constraint, constrains the release of energy to blast the cannon ball down the bore of the cannon. Thermodynamic work is done on the cannon ball. Therefore, in the absence of constraints on the release of energy in a non-equilibrium process, no thermodynamic work can be done, (19).
Newton does not tell us where the boundary conditions come from. The cannon in the example is the boundary condition. But where did the cannon come from? The critical answer is that thermodynamic work was required to assemble the cannon. We may conclude: No Constants, No Work. But it often takes work to construct the relevant constraint. Hence: No Constraints, No Work. No Work, No Constraints. This Work-Constraint cycle is a new issue, (19).
Maël Montévil and Matteo Mossio in 2015 first defined Constraint Closure, (17):
Consider a system with three non-equilibrium processes, 1, 2, and 3. Consider three constraints, A, B, and C. Let A constrain the release of energy in process 1 to construct a B. Let B constrain the release of energy in process 2 to construct a C. Let C constrain the release of energy in process 3 to construct an A (see Figures 1a, 1b and 2).
The above system achieves a remarkable property: Constraint Closure. The set of constraints, here A, B, and C, constrain the release of energy of a set of processes, here 1, 2 and 3, into the few degrees of freedom that therefore do thermodynamic work construct the very same set of constraints, A, B, and C! This system literally does the thermodynamic work to construct itself by constructing its own boundary condition constraints on the release of energy that construct the same boundary conditions.
Constraint closure is an entirely new concept. We construct our automobiles. An automobile is an elaborate arrangement of parts that constrain the release of energy of parts that impinge on other parts. Gas explodes, pistons move, wheels turn. But automobiles do not construct their own boundary condition constraints on the release of energy.
All collectively autocatalytic molecular reaction systems achieve both catalytic closure and constraint closure. All are Kantian Wholes. For example, in the 9-peptide collectively autocatalytic set in figure 2, each peptide acts as a ligase by binding the two fragments of the next peptide. By orienting the two fragments, the peptide as a ligase lowers the activation barrier to the ligation of the two fragments to make a second copy of the next peptide. Thermodynamic work is done to construct the next peptide as a peptide bond is formed. Because this is true of all the reactions in this collectively autocatalytic peptide system, the system – as a Whole – achieves both Catalytic Closure and Constraint Closure. The system constructs itself. And the system is also a Kantian Whole.
It is of the deepest importance that all living cells achieve constraint closure. Cells construct the very boundary conditions on the release of energy that constructs the very same boundary conditions. Cells construct themselves. Computers and locomotives do not construct themselves.
Reproducing cells are fundamentally not von Neumann’s self-reproducing automata, (20). These are based on a “Universal Constructor.” To construct anything specific, the Universal Constructor requires specific “Instructions.” These are encoded in a physical system placed inside the Universal Constructor. The physically embodied instructions play dual roles: They are used to construct a copy of the Universal Constructor into which a physical copy of the physical Instructions is constructed and then inserted. The dual roles of the physical Instructions constitute precisely the distinction between software and hardware. In sharpest contrast, a living cell, via catalytic and constraint closure, constructs specifically itself. A cell is not a universal constructor requiring separate Instructions. The self-reproducing 9-peptide set in figure 2 has no separatable “Instructions” that encode its formation. The concepts of software and hardware here are void.
Paul Davies, (21), points out that, in the context of a living cell, genes together with the transcription and translation apparatus are, in fact, a universal constructor for all possible encoded polypeptides. The genes can be regarded as a set of instructions. However, the living cell in which the genes are located is not itself a universal constructor. It constructs specifically itself. Were each of its several thousand genes substituted by a random DNA sequence encoding some random polypeptide, the cell synthesizing these novel proteins would almost surely perish.
Living organisms have evolved to form nested Kantian Wholes. A prokaryote is a first order Kantian Whole. A eukaryotic cell, a symbiont with mitochondria and chloroplasts, (22, 23), is a second order Kantian Whole containing first order Kantian Wholes. A multi-celled organism is a third order Kantian Whole containing second order and first order Kantian Wholes.
This paper is available on arxiv under CC BY 4.0 DEED license.