by Pross, Addy
Life’s far-from-equilibrium state
Earlier we discussed how the emergence of life’s organized complexity constitutes a thermodynamic puzzle. But there is another facet of life’s nature that is related to that complexity, which is also troubling with respect to the Second Law of Thermodynamics—its far-from-equilibrium state. Consider a bird that is hovering in space, maintaining an almost stationary position by flapping its wings. Clearly that bird is in an unstable state. If it were to stop flapping its wings, it would drop to the ground. However, that bird is able to maintain its unstable state, suspended in mid-air by the continual expenditure of energy. By constantly flapping its wings the bird is essentially pushing down on the air, and so is able to overcome the earth’s gravitational pull.
The example of the hovering bird and its unstable state might seem to be a transient moment, of no general significance. But from a purely energetic point of view the hovering bird’s unstable state is actually a metaphor for all living things. Consider the energetics of the simplest life form, a bacterial cell. That cell, from a thermodynamic point of view, is also unstable and exists in what is termed a far-from-equilibrium state in that it also must continuously expend energy to maintain that state. There are many aspects to that far-from-equilibrium state but to illustrate the point we will just describe one—the existence and maintenance of ion concentration gradients in living cells. Let us describe what that means. You dissolve some table salt, sodium chloride with the chemical formula NaCl, in water, and what happens is that the crystals of salt break up into their two constituent ions, the sodium ion, Na+, and the chloride ion, Cl-. Initially the concentrations of the two ions in solution would not be uniform, but would be higher near the point of dissolution. After some time, however, the ions would, by diffusion, distribute themselves evenly throughout the solution. That is, yet again, an example of the operation of the Second Law. A situation where there is a high concentration in one part of the solution and a low concentration in another part would be unstable compared to a uniform distribution and the Second Law is quick to correct this non-uniform ion distribution.
For living cells, however, inherently unstable ion concentration gradients are essential for many physiological functions so a nonuniform ion distribution, termed an ion concentration gradient, exists between the cell’s interior and its exterior, despite the Second Law, and that gradient is maintained over time. How can that be? In order to maintain inherently unstable concentration gradients over time the cell has to operate ion pumps, pumping ions against the gradient—just like the bird flapping its wings to stay aloft. Of course, in order to operate those ion pumps, the cell must utilize energy, and that energy has to be supplied to the cell in some form, as discussed earlier.
In other words, there is no thermodynamic mystery in the ability of cells to maintain that far-from-equilibrium state—they can do so by the continual expenditure of energy that is constantly supplied by the environment. However, there is a deep mystery hidden in the scheme we’ve just described, even if thermodynamically speaking the energy book-keeping has been meticulously maintained. Just how could far-from-equilibrium chemical systems have come about in the first place? If, as we believe, chemical processes led to the emergence of life on earth, how could chemical processes on the prebiotic earth that would be driven toward their equilibrium state, meaning toward chemical systems of low energy, have led to the emergence of complex, high-energy, far-from-equilibrium systems? Recall, the Second Law states that all systems seek to become more stable, yet in the process of emergence exactly the opposite must have taken place. In the context of the Second Law the emergence of unstable, far-from-equilibrium systems might be paraphrased: you can’t get there from here. But we did! The troubling question is then how did we?
Life’s chiral nature
Many of the molecules found in living systems are chiral, meaning that the molecule’s mirror image is not superimposable on the molecule itself. Our two hands reflect that quality—a left hand is the mirror image of a right hand, but the two hands are not superimposable on one another (Fig. 1). The term ‘handedness’ is in fact a commonly used metaphor to express this characteristic of chirality in a molecule, and in order to distinguish between these two chiral forms, different classifications are possible. One of the earlier ones, still prevalent in biology today, is the D, L classification, where one chiral molecule is labelled D (for dextro, or right-handed) and its mirror image, L (for levo, or left-handed), based on its spatial relationship to the organic substance, glyceraldehyde. The point is that the physical and chemical properties of two chiral molecules, D and L, are identical (though there are some exceptions that we need not concern ourselves with here). That also suggests that in an arbitrary environment the two chiral molecules should be present in equal amounts. If, however, for whatever reason we start off with a quantity of some chiral material of a single chirality, say all D, then that same Second Law of Thermodynamics discussed earlier, tells us, that given enough time, that material of single chirality will become racemic, meaning that the material will end up consisting of equal quantities of D and L forms (due to slow D to L and L to D interconversion). Simply, a racemic mixture is more stable than a single chiral form—it is more disordered, and therefore will tend to be established given enough time.
Fig. 1. Handedness associated with chiral objects. An object is chiral if its mirror image is not superimposable on itself.
We commenced this topic with the statement that many of the molecules of life are chiral. The amino acid building blocks from which all proteins are constructed, and sugars, from which nucleic acids and carbohydrates are composed, are all chiral. What is important, however, is that within living systems only one chiral form of the two possible chiral forms is present—biological sugars are almost invariably D-sugars, while amino acids are almost invariably L-amino acids. Living systems are universally homochiral (meaning of just one chirality). But this homochirality raises two fundamental questions. First, how did the homochirality of life emerge in the first place? Given the chiral nature of many objects in the world, how did homochirality of living things come about from a world that is intrinsically heterochiral, or, put differently, how did a world with its inherent two-handedness become single-handed within its biological part? And, second, once homochiral systems did emerge by some means, how can its maintenance be explained, given that heterochirality (an equal mixture of two chiral forms) is inherently more stable than homochirality? In that sense the homochiral nature of life represents yet another manifestation of life’s unstable and far-from-equilibrium character described earlier.
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The above detailed description of living states and their unique characteristics should serve as a stark reminder how strikingly different living and non-living systems actually are. Actually that in itself would not be a problem. Within the inanimate world different material forms can also express very different properties. Some are solid, some liquid, some gases, some conduct electricity, some don’t. Some are coloured, some are colourless. But these differences are readily explained by basic chemical theory. Consider, for example, the three traditional states of matter of water—ice, liquid water, steam. The first is a brittle crystalline solid, the second a clear colourless liquid, and the third an invisible gas—you can’t get much more different than that! But despite the dramatically different properties of the three states, we fully ‘understand’ those three states of matter. No mystery, no confusion.
So what is the basis for that understanding? Our understanding is based on our molecular view of matter and the associated kinetic theory which tell us that the states of matter depend on the magnitude of the forces operating between the individual molecules. The stronger those intermolecular forces, the more likely the substance will be solid. Of course the temperature of the material also has a bearing on the state of matter that is obtained. The higher the temperature, the more likely the material will be gaseous, due to the higher kinetic e
nergy of the individual molecules. Thus the particular properties of ice, water, steam, derive directly from our molecular view of matter; the physical sciences have provided us with a pattern that enables us to convincingly relate the three states of matter to each other. Most significantly, the final and definitive confirmation that we do indeed ‘understand’ the three states of matter comes about through our ability to readily convert one state to another. Indeed, as predicted by what are termed phase diagrams, we can bring about those transformations in different ways. We can convert ice to water by either applying pressure or by heating, and we are able to convert ice to steam without having to pass through the water phase. In summary then, we say we ‘understand’ the three states of matter, solid, liquid, gas, because we can (a) explain the different properties of those different states in fundamental molecular terms, and (b) most importantly, our understanding provides us with control over the system in question—we know different ways of converting one state to another.
With respect to the biological world, however, our current understanding of material systems is unable to address life’s unique characteristics that we’ve discussed in some detail. Simply put, within the material world there exists an entire class of material systems—the biological class—that exhibits a distinct pattern of behaviour that remains unexplained in chemical terms. And, paradoxically, that lack of understanding accompanies us despite the fact that the intricate mechanisms of biological function are increasingly understood. Somehow we know more and more of the cell’s mechanisms, yet that molecular knowledge seems to bring us no closer to understanding the essence of biological reality. We see lots and lots of trees, but a view of the forest remains frustratingly obscure. Understanding life will require that we are able to offer unambiguous explanations for life’s unique characteristics. That is one key challenge this book will attempt to address.
2
The Quest for a Theory of Life
In the previous chapter, we highlighted life’s puzzling characteristics and described our inability to explain those characteristics in simple chemical terms. Not surprisingly, given the fundamental nature of the problem, attempts to understand life have weighed upon humankind for several millennia, so let us briefly review the central concepts that have moulded our thinking through the ages. Aristotle’s ideas, going back over 2,000 years, have been particularly influential as they stemmed directly from his extensive studies of living things—Aristotle was a dedicated biologist both in practice and in spirit. That detailed observation of living things was responsible for what might be considered his most important contribution to scientific thought—his teleological view of nature, a view of such powerful persuasion that it ended up dominating Western thinking for over two millennia.
Simply put, Aristotle saw in the processes by which life is generated and maintained one that indicates them to be goal directed. Every aspect of reproduction and embryonic development, for example, exemplifies that purposeful and goal-directed character. Given that purpose was so clearly associated with such a wide variety of material forms (though all examples came from the biological world), it only seemed logical to conclude that an underlying purpose was associated with all material forms, biological and non-biological (Aristotle’s famous Final Cause). Indeed, that is the essence of Aristotle’s teleological view—that there is an underlying purpose to the workings of nature, that purpose governs the cosmos as a whole. Given the bountiful biological evidence for Aristotle’s teleological argument, in retrospect it is quite understandable that teleological thinking held up largely uncontested for over two millennia.
But then in the sixteenth century the beginnings of an intellectual stirring took place which before too long built up into a tsunami, an intellectual storm that transformed the scientific landscape of the time. What is now termed the modern scientific revolution, whose central figures include Copernicus, Descartes, Galileo, Newton, and Bacon, radically changed mankind’s perception of the universe and his proper place in it. Its major accomplishment: the long-standing teleological view of the universe underwent a dramatic reassessment and, in scientific quarters at least, was effectively discarded. In what was a dramatic turnaround from those 2,000 years of deeply entrenched and established thinking, that revolution dismissed the idea of an underlying purpose in nature, and replaced it by a view—indeed, the very essence of the modern scientific revolution—that nature is objective, that there is no underlying purpose to the natural order. The scientific and philosophic implications of that revolution cannot be overstated. Jacques Monod, in fact, considers that idea the single most important idea offered by man over the 150,000–200,000 years that he has inhabited the planet. That single idea propelled mankind into a new conceptual reality, one whose ultimate significance and impact we have yet to fully discover. But, paradoxically, that revolutionary idea, together with the accompanying change in man’s perception of the universe, only served to raise serious difficulties with regard to the life issue. Indeed the change in scientific perception ended up accentuating the life riddle by the creation of what appeared to be undeniable contradictions within the new scientific thinking. Prior to the modern scientific revolution a unity of sorts could be found in man’s view of the cosmos; teleology encompassed both the animate and inanimate worlds. But as a direct result of that revolution, the need to explain the existence of two worlds, and the nature of the relationship between those two worlds, necessarily arose. Remarkably then, the modern scientific revolution was not only unable to satisfy mankind’s relentless urge to find his proper place in the universe, but placed new and seemingly greater obstacles along the path to an improved understanding of the material world, a world that necessarily incorporates both animate and inanimate.
The next major step in this ongoing saga was the 1859 landmark publication of Charles Darwin’s On the Origin of Species. Remarkably, Darwin’s theory of evolution, though offering a grand unification of biology, only served to widen the chasm separating animate and inanimate. As previously mentioned, the scientific revolution of the seventeenth century was slow in coming about because Aristotle’s teleological argument was so persuasive, so logical, so empirically based—the world around us simply exudes endless examples of purposeful design, though, of course, that entire edifice of purpose rests on a biological foundation. In his paradigm-shattering thesis, Darwin swept away the most compelling basis for believing in a teleological universe by the profound insight that a simple mechanistic explanation—natural selection—lay behind the emergence of purposeful design in living systems. Through his principle of natural selection, Darwin was able to extend and reinforce the scientific revolution, a revolution based on the axiomatic premiss of an objective universe, into that one area where it had seemed awkwardly inapplicable—into biology. Following that epoch-making contribution, cosmic teleology, at least in scientific circles, was finally laid to rest.
However, though Darwin did provide a ‘physical’ explanation as to how simple life evolved into increasingly complex life, Darwin did not explain, or even attempt to explain, the manner by which inanimate matter was transformed into simple life. Interestingly, that problematic omission was already obvious during Darwin’s time, notably by Darwin himself. In a letter to a botanist colleague he remarked: ‘it is mere rubbish thinking at present of the origin of life; one might as well think of the origin of matter’. Darwin deliberately side-stepped the challenge, recognizing that it could not be adequately addressed within the existing state of knowledge. Ernst Haeckel, one of Darwin’s contemporaries, put it rather less kindly with his comment: ‘the chief defect of the Darwinian theory is that it throws no light on the origin of the primitive organism—probably a simple cell—from which all the others have descended. When Darwin assumes a special creative act for this first species, he is not consistent, and, I think, not quite sincere …’7 The central question of how life emerged—how design, function, and purpose were generated and incorporated into non-living matter, remained unres
olved, a perpetual thorn in the side of the physical sciences.
The dramatic advances in physics that took place in the first decades of the twentieth century failed in their turn to clarify the issue. Indeed, in 1933, Niels Bohr, one of the fathers of atomic theory, in a famous ‘Light and Life’ lecture, went as far as to propose ‘that life is consistent with, but undecidable or unknowable by human reasoning from physics and chemistry’.8 Effectively, Bohr extended what he perceived as the ‘irrationality’ of quantum theory, one that physicists were forced to accept and accommodate, to biological systems as well. A kind of intrinsic biological irrationality! Living and non-living things can exist in two kinds of material form, and that is that. Erwin Schrödinger, the father of quantum mechanics, whose provocative little book, What is Life?,9 we mentioned earlier, was particularly puzzled by life’s strange thermodynamic behaviour. Simply, modern physics and biology appeared quite at odds—fundamentally incompatible. Schrödinger found himself following Bohr’s line of reasoning, and concluded, rather enigmatically, that living matter, while not eluding the established laws of physics, was likely to involve ‘other laws of physics’ hitherto unknown.