What is Life?:How chemistry becomes biology (21 page)

In a recent theoretical simulation, Emmanuel Tannebaum and Nathaniel Wagner, two colleagues in the chemistry department at Ben Gurion University, and myself, have demonstrated that a replicating molecule that underwent some chance mutation that enabled it to capture energy, say, light energy, in a primitive kind
of photosynthesis, would be able to out-compete a molecular replicator that lacked such a capability and drive it to extinction.
⁶¹
This could even be true if the energy-gathering replicator was intrinsically slower! How can that be? The process of replication requires that the building blocks from which the molecular copy is composed be chemically activated. Activation is necessary to enable the building blocks to link up once they have locked into place on the template molecule. That’s a Second Law requirement and it must be obeyed. However activated (high-energy) building blocks are likely to be in short supply compared to unactivated (low-energy) ones. So a non-metabolic replicator (without an energy-gathering capability) would quickly use up the available quantity of activated building blocks at which point the replication reaction would cease. If, however, the replicating molecule is metabolic (i.e., it possesses an energy-gathering system), then that replicating molecule, by acquiring energy, could transmit that energy to the building blocks that have attached to it, thereby activating them. In other words, the existence of an energy-gathering capability within the replicator molecule can effectively
increase
the availability of activated building blocks, thereby facilitating the replication reaction for the metabolic replicator.

The more general point is that the existence of an energy-gathering capability within a replicating entity effectively ‘frees’ that entity from the constraints of the Second Law in much the same way that a car engine ‘frees’ a car from gravitational constraints. A motorized vehicle is not restricted to merely rolling downhill, but thanks to an external energy source (gasoline), can travel uphill as well. In other words, just as a motorized vehicle is a more effective vehicle for travel, so a replicator that can gather
energy will likely be a more successful replicator than one that cannot. The importance of the simulation described above is that it demonstrates that a replicating system that acquires
an energy-gathering capability by a chance mutation would be more stable in a DKS sense and would therefore be selected for over one without that capability.
Until now we had considered structural complexification as the primary way of enhancing DKS, but we can now see that complexification of a different kind—metabolic complexification (in the energy-gathering sense)—could also have the same DKS enhancing effect.
In fact, the moment some non-metabolic (downhill) replicator acquired an energy-gathering capability, could be thought of as the moment that life began.
At that moment the replicating system would be free to pursue its replicating ‘agenda’ despite associated energy costs, and, significantly, through the incorporation of that energy-gathering system the conflicting requirements of DKS and the Second Law would be accommodated. The means by which
thermodynamically unstable,
but
DKS stable
entities could emerge is clarified. The problem that troubled Erwin Schrödinger and other physicists would seem to have a feasible solution.

In the light of our discussions on the origin of life and the theory of life presented, we can now reassess the ‘metabolism first–replication first’ dichotomy, a question that has plagued the origin of life debate for several decades now. As we will now see, the unification of abiogenesis and biological evolution as one process may largely resolve the uncertainty at the base of that debate. The underlying issue is whether template replication or a primitive metabolism
(simple autocatalytic cycle formation) would have been the central element in the emergence of life. Recall, the ‘replication first’ school considers a chain-like molecule, such as RNA, capable of replication through a template-type mechanism, as the source of life’s emergence on earth, while the ‘metabolism first’ school believes that a simple (holistically) autocatalytic cycle would have been necessary in order to create a self-replicating system. A consideration of Gerald Joyce’s insightful experiments on RNA replication provides a hint as to the feasible resolution of the issue. Recall, a single RNA molecule was unable to replicate in a robust way, but a two-molecule network
was
able to do so. This key result suggests that both template-directed autocatalysis
and
cycle formation may well have been critical elements in the emergence of life,
most likely closely synchronized.
Simply put,
complexification (i.e., the establishment of reaction cycles) could not have come about without replication, and template replication without complexification had nowhere to go.
We are suggesting then that the ‘replication first–metabolism first’ dichotomy, as a fundamental issue in the origin of life debate, may no longer be of real relevance, and that the two conflicting approaches should be replaced by a bridging
replication and metabolism together
scenario. This Solomon-like resolution suggests that replication
and
the emergence of a primitive metabolism (a simple autocatalytic cycle) were both crucial elements at the very earliest stages of life’s emergence. Only in combination was life able to emerge from its simple inanimate beginnings.

We have presented many pieces of a highly intricate puzzle—the life puzzle, and in this final chapter we will attempt to piece the puzzle together and outline a theory of life that can offer answers to Schrödinger’s simple ‘what is life’ question. The test of the theory will be relatively easy. It would need to explain in simple chemical terms why life has the special properties and characteristics that it has, to clarify the principles that would explain the process by which it emerged from non-life, and at least attempt to offer a broad strategy for its synthesis from its molecular building blocks.

Before summarizing the elements that make up our theory of life, we must not forget that there exists a well-established theory of matter—quantum theory, a theory that in principle at least can predict the properties and future behaviour of
any
chemical system. That might suggest that a theory of life should just be part of that more general theory. Formally it is, but in a way that makes the life issue inaccessible. In practice quantum theory can only deal with chemical systems of moderate size, and biological systems in their
totality are way too complicated to be treated in that fundamental way. Go to a computational quantum chemist and ask him to solve a biological problem that requires him to explicitly treat the system’s full complexity and he will likely just grimace and walk away. So a separate theory of life is needed. Separate, but not independent. The theory of life described here is but a smaller Russian doll within the bigger ‘theory of matter’ doll. Importantly, however, and as emphasized earlier in the text,
despite
life’s complexity, a theory of life can be postulated, with the basis for such a theory being the presumption that life began simple, and that life’s essence reflects its simple beginnings. By probing what we believe to be the equivalent of life’s simple beginnings, we are able to grasp biology’s core and address some of biology’s most basic questions. But to do that, to get to the core, we had to cut through the many layers of complexity to uncover what lies hidden inside, and that was done by peeling away the layers of complexity along a reverse time
axis.
Complexity was built up over time, step by step, so we had to conceptually reverse that process until the core was reached. Only by reaching back into the process by which life on earth emerged can the essence of what it is to be alive be uncovered. Once we get to that core, we may begin to understand why life emerged, and have a clearer view of what life is.

That approach leads us to systems chemistry, the chemistry of simple replicating systems that we discussed in detail in earlier chapters. The study of simple replicating systems has revealed an extraordinary connection—that Darwinian theory, that quintessential biological principle, can be incorporated into a more general chemical theory of evolution, one that encompasses both living and non-living systems. It is that integration that forms the basis of the
theory of life I propose. The realization that chemistry and biology connect up in this fundamental way will prove, we believe, to have profound implications, some of which are already apparent, for example, the unification of abiogenesis and biological evolution. Abiogenesis and biological evolution are one continuous process—abiogenesis (the transformation of non-living matter to earliest life) is the low-complexity phase, biological evolution is just the high-complexity phase. That unification serves to clarify the physical nature of the evolutionary process that led from simple abiotic beginnings right through to complex life. By uncovering the process that connects inanimate to animate, the essence of what it is to be alive begins to materialize. The emergence of life was initiated by the emergence of a simple replicating system, because that seemingly inconsequential event opened the door to a distinctly different kind of chemistry—replicative chemistry. Entering the world of replicative chemistry reveals the existence of that other kind of stability in nature, the dynamic kinetic stability of things that are good at making more of themselves. Exploring the world of replicative chemistry helps explain why a simple primordial replicating system would have been expected to complexify over time. The reason: to increase its stability—its dynamic kinetic stability (DKS).

Yes, living systems involve chemical reactions, lots of them, but the essence of life, the process that started it all off, was replication. And what makes that replication reaction special is not what it produces but how much it produces. If a further reminder of the special nature of the replication reaction is needed, consider a single replicating molecule, weighing just 10
^-21
grams. If it were to replicate once a minute, then, in under five hours that replicating molecule would have grown (in principle, of course) into a mass
exceeding that of the entire universe! Think about that! One molecule replicating not too rapidly, would devour the entire material resources of the universe in a few hours! The point is that the replication reaction is unique and totally different from every other chemical reaction that appears in a chemistry textbook because of that awe-inspiring kinetic power—a mathematical power that turns the conventional rules of chemistry on their heads. The Second Law of Thermodynamics is, of course, fully applicable to replicating systems, but the enormous kinetic power of replication ends up seemingly circumventing that ubiquitous Second Law. The concept of stability in chemistry is fundamental, but that extraordinary kinetic power creates a distinctly different kind of stability in chemistry from the ones we are familiar with. As discussed in
chapter 4
, in ‘regular’ chemistry matter is stable if it
doesn’t
react. But in the world of replicating systems, matter is stable (in the sense of being persistent) if it does react, to make more of itself. And in this persistent sense, matter that is better at making more of itself is more stable than matter that isn’t.

That is the essence of the DKS concept. But that means that in the world of replicators, reactions follow a
Second Law analogue—
populations of poorer replicators continually react so as to become more effective (more stable) replicators, though, of course, only in a manner that is consistent with the Second Law itself. And the kind of chemistry that results from reactions in this ‘other world’, the replicative world, is so different from those in the ‘regular’ world that much of it goes under a different name—biology. Biology then is just a particularly complex kind of replicative chemistry and the living state can be thought of as a new state of matter, the
replicative state of matter,
whose properties derive from the special kind of
stability that characterizes replicating entities—DKS. That leads to the following working definition of life:
a self-sustaining kinetically stable dynamic reaction network derived from the replication reaction.
Each word in the definition imparts an important element to the definition. ‘Self-sustaining’ means that the system must have an energy-gathering capability in order to satisfy the requirements of the overriding Second Law. The terms ‘kinetically stable’ and ‘dynamic’ describe the characteristics of that other stability kind, and the words ‘network’ and ‘replication’ are self-explanatory, though we will shortly expand on the network aspect of life, one of considerable importance. Of course, from that perspective, death is just the reversion of a system from the kinetic, replicative world back to the thermodynamic world, the world of ‘regular’ chemistry.

So there we have it. Even though life is an extraordinarily complex phenomenon, the life principle is surprisingly simple. Life is just the resultant network of chemical reactions that emerges from the continuing cycle of replication, mutation, complexification, and selection, when it operates on particular chain-like molecules—in the case of life on Earth, the nucleic acids. It is possible that other chemical systems could also exhibit this property, but so far this question has yet to be explored experimentally. Life then is just the chemical consequences that derive from the power of exponential growth operating on certain replicating chemical systems.

The theoretical ideas at the heart of the DKS concept are far from new. Thomas Malthus fully appreciated the mathematical power of exponentials, as described in his classic work ‘An Essay on the Principle of Population’ published in 1798, and Alfred Lotka’s early work on kinetic theory going back to 1910 fully appreciated the kinetic consequences of exponential growth on both chemical and
biological systems. Paradoxically that is all the ‘hard theory’ one needs to know to understand life. Note, no quantum mechanics involved—that murky area of physics and chemistry that continues to strain human credulity. In that sense life is a
classical
phenomenon and the tendency of past physicists to attribute life’s character to matter’s fundamental quantum nature appears unnecessary. Though the importance of quantum effects in many areas of chemistry is undisputed, it is surprising how much organic chemistry and biochemistry is understandable without the need for quantum thinking. It is the
complexity
of life that has created confusion and blocked important early insights, particularly those of Malthus, Lotka, and Troland, and more recently, those of Manfred Eigen and Peter Schuster. So the relationship between the life phenomenon and its extraordinary complexity can now be stated: complexity is not the
cause
nor the
essence
of the life phenomenon, complexity is its
consequence.
Replication induced complexity, not the other way around. It is the coupling of long-standing and basic theoretical ideas associated with autocatalytic systems together with the insights from recent studies of simple replicating systems, and the networks they establish, that enables the elements of the life puzzle to be finally pieced together.