by Pross, Addy
I write that partly tongue in cheek because life’s diversity has offered us an unimaginably large array of forms, from microscopic bacteria through to blue whales, so it is hard to see how life forms of any other kind would strike us as fundamentally different in their external appearance, and certainly no more alien looking than many of life’s existing forms. More to the point, however, is the fact that life’s morphology appears to be based on what living things require it to be, rather than some directive that comes from its underlying chemistry. Cars made from fibreglass, aluminium, or steel don’t look too different from one another because their appearance is based on the shape cars need to be in order to function as cars. All cars, regardless of the material from which they are made, require an external shell in which to house the motor and create a cabin for passengers to sit in. They all possess windows so the driver can see where he is going, and wheels to minimize friction. That is true whether the cars are made in the US or in China, whether the windows are glass or plastic, whether the engine is electric or gasoline. In the same way, life forms that emerged from some replicating entity that did not belong to the nucleic acid family, but were able to complexify and evolve toward replicating entities of greater DKS, would likely utilize the same universal concepts that nucleic acid-based biochemistry discovered. Depending on the extent to which that other life form had evolved, it would also express network characteristics, and may have discovered the replicative value of a cell structure, in which the cell’s functional parts with its replicative and metabolic capabilities would be incorporated. The theory of life presented here is not one based on material, but one based on process, and therefore the nature of the material would be secondary, possibly even incidental, in governing life’s underlying characteristics.
Synthesizing life
Which brings us to the most intriguing of questions—how would one synthesize a simple living system? To this question there is no simple answer. If the theory of life presented here teaches us anything, it is that the synthesis of some entity that would possess the characteristics of a primitive life form, say a protocell, faces enormous difficulties. Let’s see what these are. I will begin with some observations.
The relationship between living and non-living systems is particularly fascinating in at least one respect. It is so easy to transform living systems into non-living ones, but, as we know all too well, the process is not reversible—life is so easy to destroy, but (chemically speaking) so hard to make. That simple fact in itself is highly informative. The problem with the synthesis of a living system is not one of material, but, as noted, one of organization. You can have all the components of a living cell available, but packaging it so that it behaves as a living entity is where the difficulty lies. So what is the problem? Life is a dynamic state of matter meaning that the biomolecules that make up the living cell are in a constant state of flux. A simple physical analogy that captures this dynamic character would be that of a juggler juggling several balls. That dynamic state is of course identical in a material sense to the one in which a man stands next to those balls, which are resting on the ground. But the difference is profound. How easy it is to take a juggler juggling several balls and to convert him into the non-juggling state, one in which all the balls are lying on the ground. A hefty push and you are there! A man standing next to five balls would be the metaphor for death. Of course going in the other direction is not that simple. You cannot simply throw five balls in one go at a person and expect him to enter the juggling state. That won’t work. In the same way, if you take all the components of a living cell and mix them together, you won’t end up with a living cell. At very best, if all the bits and pieces end up in the right place, you’ll end up with the equivalent of a dead cell. You’ll end up with a clump of stuff—a thermodynamic aggregate. Recall, however, that the living cell is in a dynamic, far-from-equilibrium state, like that bird flapping its wings to stay airborne. Simply bringing together the components that can potentially make up an integrated and dynamic system that we would classify as alive won’t lead to that special organizational and dynamic character that we recognize as life.
So let us return to our juggler analogy to see what kind of strategy might work. How does one enter the juggling state? The answer—step by step. Initially you toss two balls at the juggler, then a third, then a fourth, one step at a time. You start off simple and you add complexity bit by bit. That’s how evolution did it—step by step, from simple and less stable, to complex and more stable. So how to make life? Enter the replicative dynamic state at a low level of complexity and then proceed to complexify, one step at a time. That, of course, is easier said than done. But don’t be fooled by morphology. Life, even in its very simplest form, is far more than just a replicating entity in a bag. If a much simpler individual life form were capable of a physical existence, then it stands to reason that we would see such life forms as part of the replicative array of possibilities, as part of the passing parade, but we don’t. The absence of such entities speaks volumes for their physical feasibility. Given life’s dynamic nature, the synthesis of a chemical system expressing the dynamic characteristics of life would be an important step forward. Recently Sijbren Otto, an innovative systems chemist from the University of Groningen with a Ph.D. student, Elio Mattia, have begun exploring possible means of generating such dynamic kinetically stable chemical systems, but the challenges are great. I will conclude by saying that the synthesis of a simple chemical aggregate that exhibits lifelike characteristics, primarily self-sustained replication, appears to be a highly ambitious target at the present time.
How did life emerge?
We stressed early in this book that if we want to understand what life is, we have to understand the process by which it emerged. And what have we discovered? That thanks to recent findings in systems chemistry, the origin of life problem, at least in its ahistoric sense, may be largely resolved. There is now good reason to believe that abiogenesis and Darwinian evolution are just one process. So, if we believe we understand biological evolution, and broadly speaking we do, then we also understand abiogenesis. The historical questions—the what, where, and when questions, will continue to tease and torment us for the foreseeable future, as the ability of scientific study and reasoning to uncover the historical record is limited. However, just as the historical details of Darwinian evolution—what species lived when—are secondary to the theoretical framework, so the historical details of life’s emergence, though fascinating in their own right, could also be considered of secondary importance. A solution to the primary question exists and is breathtakingly simple: life on earth emerged through the enormous kinetic power of the replication reaction acting on unidentified, but simple replicating systems, apparently composed of chain-like oligomeric substances, RNA or RNA-like, capable of mutation and complexification. That process of complexification took place because it resulted in the enhancement of their stability—not their thermodynamic stability, but rather the relevant stability in the world of replicating systems, their DKS. What is particularly satisfying in this explanation is that the resolution of the origin of life problem (in the ahistorical sense) dovetails seamlessly with Charles Darwin’s momentous ideas on biological evolution. In effect the physical problem of how life on earth emerged may be understood by reformulating and extending Charles Darwin’s theory of biological evolution to include molecular systems. By reinterpreting and translating the central biological terms that underlie biological evolution into the corresponding chemical terms, it becomes evident that abiogenesis and biological evolution are indeed one single chemical process.64
Of course, as we pointed out above, that explanation does not tell us what actual events took place on the earth 4 billion years ago. But then Darwin’s theory of evolution does not tell us the specific historic path from earliest life to today’s diverse and complex life either. That wasn’t its purpose. Filling in the historic record was left to palaeontology and phylogenetic analysis. Darwin’s co
ntribution was in delineating ahistoric principles. He revealed to us that biological evolution is a natural process, that all living things are related and descended from some common ancestor, and that a simple mechanism, natural selection, operating on mutating replicators, can explain the basis for that entire process. What has been argued here is that the Darwinian thesis can be extended to inanimate matter enabling the problem of abiogenesis to be resolved in the same ahistorical manner. It is staggering to realize that Darwin, in his genius, already foresaw where his evolutionary principles might ultimately lead. His comment in his 1882 letter to George Wallich ‘that the principle of continuity renders it probable that the principle of life will hereafter be shown to be part, or consequence, of some general law’ seems almost clairvoyant in its precision and clarity. Darwin didn’t know about replicating molecules or kinetic selection or the mechanism for biological hereditary or those insightful experiments in systems chemistry of Gerald Joyce, Günter von Kiedrowski, Reza Ghadiri, Gonen Ashkenasy, Sijbren Otto, and other fine chemists, but well over a century after those words were written it seems Darwin was, yet again, right on the mark.
Life as a network
Having clarified the central elements in the process of life’s emergence from inanimate matter, we are now ready to address a fascinating and central feature of living things, one that dramatically impacts on life’s very essence—its network character. We have already seen that life began simple and then proceeded to complexify. But what do we actually mean by ‘complexify’? The answer: network formation—from relatively simple reaction networks through to complex ones. The essence of all these networks is that they are holistically self-replicating. Life then is just a highly intricate network of chemical reactions that has maintained its autocatalytic capability, and, as already noted, that complex network emerged one step at a time starting from simpler networks. And the driving force? As discussed in earlier chapters, it is the drive toward greater DKS, itself based on the kinetic power of replication, which allows replicating chemical systems to develop into ever-increasing complex and stable forms. And now the actual nature of that complexification process can be specified—network formation. Complexification, network formation—they are effectively one and the same. Viewed in this light, life is more a process than it is a thing. Or as Carl Woese and Nigel Goldenfeld recently put it: ‘Biology is a study, not in being, but in becoming.’67 And in what medium does that network establish itself? In that extraordinary solvent, water. Water, the cosmic juice, with its unique properties68,69 is considered crucial for enabling life’s network of reactions to have become established.
I have stated that life is a network of chemical reactions, but merely by inspecting the world around us we see that the network seems to be composed of individual units—cells. Cells are the smallest discrete entities that we unambiguously term to be ‘living’. Living things can consist of these single-cell entities, or they can be multicell organisms composed of blocks of individual cells. But the network perspective on life leads to an interesting and highly pertinent question: Do individual life forms actually exist? Individual living things do seem to exist, in the sense that we are surrounded by what appear to be examples of individual life forms—birds, bees, camel, humans, and, of course, unicell life, primarily bacteria, all seemingly going about their individual business. In practice, however, that individuality is not quite as clear-cut as one might think. What we classify as individual living entities may themselves be thought of as components of a network—the ever-expanding life network. Let’s think again about those single-cell species, bacteria. We discussed earlier that in some bacterial species the colony can actually switch from a unicell format—swarms of individual bacteria—to a multicell format, where the bacteria merge together into a protoplasmic lump. That happens when resources become scarce. But those cells, whether bound together or physically separate, are constantly communicating chemically to coordinate their actions. The phenomenon of biofilms is another example of coordinated bacterial action. Bacterial behaviour highlights life’s network character. Bacterial genes destine them to be communal, not individual. Bacteria are more a network than they are a set of individuals.
Recent thinking regarding the evolutionary path that led to the modern cell fits into this general mould. Carl Woese considers early cells to have been highly communal, their evolution dominated by horizontal gene transfer.70 That is another way of saying that earlier life consisted of a tightly integrated replicative network of simpler aggregates. But, as the network evolved and complexified further, it advanced to a looser and more modular form. That’s when cells, as discrete biological entities, were born. That transition was a highly significant one—one might consider it as a phase transition.55 That morphological change from strictly communal to increasingly individual opened up a new range of evolutionary capabilities. One obvious advantage of that transition was that a replicating network whose components exhibit greater individual character would be less vulnerable to attack than a tighter interdependent network. Attack any segment of a tight network, in which all components are crucial for network replication, and the entire network will suffer. If, however, the network is made up of components that are themselves replicative, then the network can be looser and more modular. Destroy some components of a looser, more modular, network and the network is likely to survive. But that means that individuality is more a life strategy than a life characteristic. So-called individuality is just a technique that evolution has discovered, amongst many others, to enhance replicative ability and robustness. This network perspective can change the very way we think about life, and reaffirms that the life phenomenon is better understood as one of process rather than one of form, the forms being incidental manifestations of the process. Looked at in this way the life process—the replicative process—can be seen to utilize every ‘trick in the book’ in order to optimize its replicating agenda. The process chooses togetherness when that is optimal, and separateness, manifested as physical individuality, when that is the better option. Whatever works best at the given time and under the particular circumstances.
What about the role of individuality in multicell systems? Surely here one could argue that clear-cut and unambiguous cases can be recognized. However, here also that individual classification is quite problematic. Take us humans as an example. Each human is, of course, composed of billions of individual cells, some 1013 of them, and of many different kinds. Remarkably however, each human being actually consists of ten times as many bacterial cells as human ones. From a numerical point of view, we are more bacterial than human! Literally billions of these bacteria, comprising hundreds of different species, reside in our gut, in other body cavities, on our skin. Each human is more a superorganism—a giant network—than an organism.71 These bacteria may be so integral to human health that they have recently been described as the ‘forgotten organ’!72 The point is that each and every human individual, and so every multicell creature, is more an ecological network than a single living entity. Indeed, appreciating life’s inherent network character, rather than focusing on its individual character, is leading us to a new and revolutionary way of understanding disease and disease prevention, at least when viewed from the human perspective.
What about plants? Plant individuality is also questionable as they also are part of an extensive ecological network. Plants depend on bacteria for their metabolism much like animals, though by a different mechanism. Plants depend on a source of nitrogen to enable protein synthesis, but atmospheric nitrogen is relatively inert and cannot be utilized readily. It is the bacteria in the soil and in the plant’s roots that enable plants to access nitrogen in a usable form. We see then that life is more like a set of Russian dolls nestled in one another, and connected up in networks with other sets of dolls, rather than an extensive array of independent things that interact with one another. Even those bacteria that inhabit your gut are not the last link in the replicative chain, but may themselves be hosts
to lesser life forms, viruses. Viruses are non-metabolic entities that are only able to replicate by exploiting the metabolic capabilities of their host cells. Are viruses then the end of the line? In life there are always unexpected surprises. It has recently been discovered that giant viruses are abundant in nature, some larger in size than small bacteria. Interestingly, however, it has recently been found that these large viruses can themselves be infected—with small viruses. As with Russian dolls, you are never sure when you have reached the last link in the chain. Replicative chemistry is full of unexpected twists and turns.
That was the network looking down, but start from a human and look up and you see an individual who is part of a nuclear family, which, in turn, is part of an extended family, which is part of a local community, which is part of larger groups of human organization. The functioning of the network at any level is dependent on the functioning of the network both below and above. The individual merely represents a particular level of complexity within a network that involves many different levels of complexity. Take sex, for example. It catches our attention—it’s meant to. Sex tells us that we, as sexual individuals, are reproductively speaking incomplete. Biologically speaking, our individuality is actually non-existent. The individual has no future—literally. That’s why sex catches our attention in that powerful and compulsive way. But we are also emotionally incomplete and various psychological elements also connect us to the network. We obsessively need to be with others. We think we are separate, but we are one. We think of ourselves as individuals, but we are really just components of a network. So a biosphere that has overwhelmed our planet should not be interpreted in terms of an invasion by billions of individual life forms, but by an ever-expanding living network. The replicative drive leaves no stone unturned in seeking novel and creative ways to replicate and extend that network. Clearly, given the above comments, coming up with a precise definition for an individual living thing would be problematic. Would an individual have to be reproductively independent? If so, any sexual being, like you or me, would not satisfy the definition. Would a life form be considered truly individual, if it is symbiotically bound to other replicating entities, without which it cannot reproduce or even survive? Even though some components of that giant replicative network do appear to be individual, that appearance is often illusory.
