Forced Trajectories

Google Books had the first chapter of the hard-to-find Principles of Life by Tibor Ganti, famous for his chemoton model. Ganti’s prose is remarkably clear and, in my opinion, hits all the key conceptual points needed to define Life. Chapter 1, titled “Levels of Life and Death” was written circa 2000. I’ve put in a request for the book through interlibrary loan and hope to read the rest of it soon! Meanwhile, in today’s post I will quote Ganti (in italics) accompanied by my short commentary.

 

First, what distinguishes living systems from non-living systems. Tricky question. Ganti starts with discussions from Schrodinger’s famous What is Life? book.

 

All living systems – while alive – do something, work, function.

 

But other things do work and have a function. Ganti anticipates this. He also distinguishes natural systems from man-made (artificial) systems.

 

However, living things are not the only systems that ‘do something’ and also do it for long periods… rivers do their erosive work continuously… in technology, engines are also able to do work without interruption. What is common in these systems is that they are positioned between the higher and the lower potential level of some kind of energy, and, part of the energy which flows through the system is transformed to work.

 

He then hits on the crucial requirement of an energy gradient. There must be a flow of energy, and then something in the system needs to be able to extract work from that energy flow.

 

To get from random to directed work, the flow of energy must be manipulated along a series of forced trajectories within the system.

 

I think this idea of ‘forced trajectories’ is very important. I’ve been puzzling over what this should look like in a chemical ‘living’ system. There are some allusions to it in other articles and books, but I’m still fuzzy on what this means. I get the sense that there is a cascade of chemical reactions, with a particular direction or driving force. But how such a system is assembled is less-than-clear.

 

The driving force of living systems is chemical energy… However, in contrast with the situation for mechanical [or electrical] machines, the energy flow in living systems is manipulated by chemical means… In contrast with manmade technologies, where the machines are based on mechanical or electronic automata, living systems are fundamentally chemical automata. During evolution, the mechanisms of living systems have sometimes been extended using mechanical and electronic components, but their basic structures remain chemical automata. They manipulate the driving energy by chemical methods.

 

As a chemist, I strongly resonate with Ganti’s description. Of course this begs the question of how chemistry manipulates the ‘driving energy’. The second law of thermodynamics is a driving force. As a chemist, bond-breaking and bond-forming at the molecular level is the activity I consider fundamental. At the ‘body’ temperature of living organisms, the enthalpic contribution to making and breaking bonds often outweighs the entropic contribution, and a combination of both allows one to calculate the changed in free energy of reaction (delta-G!) – by definition, the maximum amount of useful work one might be able to extract from the chemical reaction. So my imagined cascade of reactions needs to have a negative delta-G, but also be arranged in a way that allows for extraction of energy for useful work. I haven’t defined ‘useful’ but it connotes an end-goal or function, thereby complicating ideas of cause, effect, time, and agency.

 

Chemical reactions can proceed with suitable intensity only in the fluid phase (gas or solution)... the continuous presence of some kind of solvent is essential. The functioning of mechanical automata is restricted to a rigorous geometrical order of their parts, and the functioning of electronic automata is also restricted to some geometric arrangement of their components. The functioning of the fluid automata is largely independent of any kind of geometrical order. It works even if the solution is stirred, or if half of it is poured into another container… Compared with mechanical and electrical automata… these properties provide living systems with highly favorable possibilities. One of these is, the capacity for reproduction – autocatalytic systems are well known in chemistry.

 

I’ve spent some time thinking about autocatalytic systems, but I hadn’t pondered the importance of being in a fluidic milieu and being ‘independent of geometrical order’ other than superficially. Ganti’s argument makes sense to me, especially if you want to have reproduction of what might be a complex system. The ‘suitable intensity’ of fluids highlights an analog system that presages control mechanisms. Or maybe I’m reading too much into this.

 

Ganti then goes on to define his minimal living system. I have no quarrel with his definition.

 

The fundamental unit (i.e. the minimal system) of biology must have some specific properties:

·      It must function under the direction of a program

·      It must reproduce itself

·      It and its progeny must be separate from the environment

 

This is followed by his description of the chemoton made up of three subsystems. Autocatalysis features importantly in all of them, and they have to work together. They cover the fundamentals we observe when we think about ‘classes’ of molecules found in a cell, the smallest autopoietic unit.

 

A chemoton consists of three different autocatalytic (i.e. reproductive) fluid automata, which are connected to each other stoichiometrically…

(1)  the metabolic subsystem [with] a reaction network of chemical compounds with mostly low molecular weight able to reproduce itself, but also the compounds needed to reproduce the other two subsystems,

(2)  a two-dimensional fluid membrane [with] the capacity for autocatalytic growth using the compounds produced by the first subsystem,

(3)  a reaction system able to produce macromolecules by template polycondensation using the compounds synthesized by the metabolic subsystem… the byproducts are also needed for the formation of the membrane. In this way, the third subsystem is able to control the working of the other two solely by stoichiometric coupling.

… the three fluid automata become a unified chemical supersystem through the forced stoichiometrical connections… unable to function without each other… but their co-operation can function.

 

I’m reminded that my focus on proto-metabolism, leading to the first subsystem, might blind me to its crucial interactions with the other two subsystems. Which might also explain why I’ve been puzzling over how to repeatedly drive autocatalytic cycles if the food molecules run out. High energy ‘food’ molecules transform to low energy waste molecules while organisms use some of the energy towards growth and repair. And if one organism’s waste is another’s food, then a natural symbiosis may sustain those organisms. You’ve gotta eat poop in the primordial soup!

 

Kinetic analysis of the elementary chemical reactions allows us to perform an exact numerical investigation of the workings of the chemotons using a computer… The fact that it is an abstract system means that its components are not restricted to particular chemical compounds. However, they must have certain stoichiometric capabilities and, they must be able to produce certain compounds, which are important for the whole system.

 

Since I’m a computational chemist, I’m encouraged by Ganti’s words. As a quantum chemist, so far I’ve focused on the easier thermodynamic parts, because determining kinetics requires calculating transition states – transient and potentially tricky to optimize. But I’m reminded that I have to worry about the kinetics – it’s a crucial piece to the story. Thermodynamic gradients may provide a driving force but kinetics is the key to ‘forced trajectories’ by providing openings to dams in strategic places.

 

The model does not contain any prescription or restriction on the speed of the chemical reactions in the system. Therefore it remains valid whether the reaction rates are determined exclusively by the concentrations of the components or are influenced by catalytic effects…

 

I take this to mean that to some extent I’m on the right track with my model-building approach. The kinetics are going to be important in some of the nitty-gritty, but I might be able to say something both useful and interesting without having to figure out all the activation barriers. Here’s Figure 1.1 from the book illustrating Ganti’s chemoton. I’ve drawn similar pictures myself.

 

There are no details of the enzymes or catalysts in the model. As I’ve been thinking about how to maintain a forced trajectory through chemical means, I’ve started experimenting (by which I mean computational tests) with ‘carrier molecules’ for shuttling energy. Not ATP, which I think came later in the game. Some are redox-neutral and easier to deal with, but I’m also trying to decide the best way to model the redox reactions that drive the incorporation of CO₂ into carbon-based biomass. H₂ is the easy reductant to use computationally, and it might be important in some cryptobiotic cases, but extant life doesn’t use molecular hydrogen as is, for good reasons.

 

This post doesn’t have a conclusion because all this is still rattling around in my mind. But my take-home message from the first chapter of Ganti’s book is to focus on ‘forced trajectories’ and think about how to build it into my computational models. Maybe when I read the rest of the book, I’ll discover that Ganti knew the answers to the questions I’m asking. Sadly, he passed away in 2009 so I won’t be able to ask him any follow-ups.