What is Life?: How Chemistry Becomes Biology (Oxford Landmark Science)

by Addy Pross

physicists are still at it, attempting to further generalize, with sophisticated formulations such as string theory and M-theory, constantly working toward the so-called final theory—the theory of everything, the ultimate pattern. Of course whether an ultimate pattern is achievable is another question, one that belongs within the realms of philosophy, not just science—a wonderful question in its own right, but one that goes well beyond the scope of this discussion.

Let us not forget the revolutionary impact of Darwin’s ideas of natural selection and common descent, ideas that were entirely qualitative in their formulation yet continue to profoundly impact on man’s view of himself to this very day. To quote the aphorism attributed to Albert Einstein: Not everything that counts can be counted, and not everything that can be counted, counts.

scientists typically use other terms, such as hypotheses, theories, laws, to mention the main ones, the difference being primarily in the degree to which the pattern has been confirmed.

As to the underlying reason for the existence of those patterns, rules, laws, generalizations, or whatever we wish to call them, science is unable and does not pretend to address such questions.

is clear that the nature of understanding within physics, a more fundamental science, is quite different from its operation within biology, whose domain is the study of inherently highly complex systems. Within physics generalizations are invariably rigorously quantified, articulated in the language of mathematics so that exceptions to the rule are not tolerated and require a reformulation of that rule. Within biology generalizations are frequently qualitative and exceptions

whatever one calls them—theories, laws, models, hypotheses, patterns—all efforts to find order in our universe can never fully capture the reality of nature. The patterns we uncover are merely reflections of that reality—some better, some worse, whose recognition brings us some sense of order to the complex world that we find ourselves in. The preceding discussion will now assist us in addressing a central issue in the continuing search for biological understanding—the issue of reduction versus holism.

The essence of the reductionist approach is simply: ‘the whole can be understood in terms of the interaction of its constituent parts’. For example, if you want to understand how a clock works then break it up into its component parts—wheels, cogs, springs, etc., and see how these work together to create the functional entity.

holism, whose philosophy can be summarized by the simple statement: ‘the whole is more than the sum of its parts’,

Holism contends that within complex systems in particular, unexpected emergent properties arise that cannot be derived by examining the individual components of the system (by emergent properties we mean that there are properties at the higher and more complex level that are not observed at lower levels).

This approach has gained considerable influence in recent years, specifically with regard to the biological sciences, due to the extraordinary complexity of even so-called ‘simple’ biological systems, and has led to the establishment of a new branch in biology—systems biology. Carl Woese’s view of biological systems as ‘complex dynamic organization’, rather than as a ‘molecular machine’ whos...

the most useful application of reductionist philosophy, when viewed as a scientific methodology, is the one termed ‘hierarchical reduction’, the idea being that phenomena at one hierarchical level can be explained using concepts taken from a lower hierarchical level.

The holistic view derives its persuasive influence from the systems theory school of thought that builds on the idea that within complex systems, systemic relations arise that produce novel and quite unpredictable characteristics.

extreme expressions of reduction, such as the one offered by Francis Crick,25 who claimed that ‘the ultimate aim of the modern movement in biology is to explain all biology in terms of physics and chemistry’. Such claims appear unrealistic for the foreseeable future, and remain an ultimate aim in just the same way that the ‘ultimate aim’ of chemistry is to predict all chemical phenomena through solving Schrödinger’s famous wave equation.

emergent properties are regularly addressed and understood through reduction.

Condensed states exhibit a variety of emergent properties that are totally absent at the single molecule level. The condensed state may be solid or liquid, it may be conducting or insulating, shiny or dull. A single molecule does not possess any of those condensed state properties. A single molecule is neither solid, nor liquid, neither shiny nor dull.

these condensed state properties are well understood based on the electronic characteristics of the individual molecules.

The oft cited claim that some properties cannot be explained by reduction because they are emergent is simply incorrect, though, of course, this does not mean that all emergent properties can be explained by reduction. Reduction as a methodology does have its limitations, as does any methodology.

All living things involve chemical reactions, thousands of them, and the living cell, the basic unit comprising all life, is a highly complex set of these reactions somehow integrated into a coordinated whole.

chemical reactions proceed such that less stable materials are transformed into more stable materials. A ball rolling down a slope is a useful analogy. Chemical reactions proceed in a ‘downhill direction’, where downhill signifies toward more stable products, products that are characterized by what is termed lower ‘free energy’. Since the free energy of water is lower than the free energy of a mixture of hydrogen and oxygen gases, the two gases react to form water, and the energy that was stored in the higher-energy hydrogen and oxygen molecules is released as heat. The reverse reaction in which water would be transformed into hydrogen and oxygen gases cannot take place spontaneously because that would be equivalent to a ball rolling uphill.

reactions will only take place if the reaction products are of lower free energy than the reactants. That determines the direction of any chemical reaction and is called the thermodynamic consideration.

reaction that is allowed thermodynamically may or may not proceed, depending on kinetic factors (the barrier height). However, a reaction that is forbidden thermodynamically cannot proceed.

a chemical reaction that combines two species into one is unfavourable from an entropic point of view since that increases the order of the system (i.e. decreases its entropy), while a reaction that breaks up a single molecule into several fragments is favoured entropically as it decreases the order (increases the entropy) of the system.

reaction in which the product and the catalyst are one and the same, i.e., the product acts as a catalyst in its own formation. Such a reaction is termed autocatalytic

the power of exponentials. The difference comes about because in the autocatalytic reaction, the rate of product formation proceeds exponentially, whereas in the catalytic reaction the rate of production proceeds linearly,

Sol Spiegelman

self-replicated, as indicated in Fig. 3c. So molecular self-replication reaction is a reality, a reaction that actually does take place, and, most importantly, is autocatalytic.

Chemical reactions will only proceed if they are downhill in a thermodynamic sense such that less stable reactants are converted into more stable products. 2. Reactions that are allowed thermodynamically may not proceed, or may proceed slowly for kinetic reasons. An energy barrier has to be overcome for the reaction to take place. 3. Molecular self-replication of template-like molecules is an established chemical reaction and is kinetically unique. Being autocatalytic, self-replication can lead to dramatic exponential amplification of that template-like molecule until resources (building blocks from which the chain is composed) are exhausted.

the supply of water remains uninterrupted) but the water comprising that fountain (or waterfall) is being turned over continually.

the stability of rivers, waterfalls, fountains, and the like, all displaying stability of a dynamic kind,

any replicating system (whether composed of replicating molecules, rabbits, or some other group of replicators) that is stable, can only be stable if its rate of formation is balanced (more or less) by its corresponding rate of decay.

that if a replicating system is found to be stable over time, it is the population of replicators that is stable, not the individual replicators that make up that population.

the stability associated with a stable population of replicating entities, whether molecules, cells, or rabbits, is of a dynamic kind, just like that of the river or fountain.

life’s dynamic character, a feature that has troubled modern-day biologists, derives directly from the dynamic character of the replication reaction.

‘regular’ chemical world a system is stable if it does not react. That is the very essence of stability—lack of reactivity. In the world of replicating systems, however, a system is stable (in the sense of being persistent and maintaining a presence) if it does react—to make more of itself, and those replicating entities that are more reactive, in that they are better at making more of themselves, are more stable (in the sense of being persistent) than those that aren’t. This is almost a paradox—greater stability is associated with greater reactivity. We therefore call the kind of stability associated with replicating systems a dynamic kinetic stability.

High stability will be facilitated by a fast rate of replication and a slow rate of decay since that will lead to a large population of replicators.

given that the kind of stability applicable in the replicating world is dynamic kinetic, not thermodynamic, the rule that effectively controls transformations within the world of replicators is not the Second Law, but one that is expressed in terms of dynamic kinetic stability. The rule is simply stated as follows: Replicating chemical systems will tend to be transformed from (dynamically) kinetically less stable to (dynamically) kinetically more stable.

Thus, on occasion, imperfect replication will lead to the formation of a mutant RNA strand. In other words, over time the solution will begin to consist of both original RNA strands as well as mutated ones. And here Spiegelman made a remarkable observation. Over time the solution began to be populated by mutant RNAs that replicated more rapidly than the original RNA strand.

Darwinian selection was found to take place at the molecular level—the RNA strands evolved. Since short RNA strands replicate more rapidly than longer RNA strands, the initial strand composed of some 4,000 nucleotides began to shorten and eventually ended up with just some 550 nucleotides.

An RNA strand in no way constitutes a living entity—it is a molecule; admittedly a biomolecule, meaning that it is a molecule of the kind normally found in living systems, but a molecule is a molecule is a molecule. And the fact that a slowly replicating molecule tends to evolve into a more rapidly replicating one is due to chemical factors, chemical kinetics to be precise. Nothing biological here—just chemistry.

there are rules that govern car function—how engines operate—that sit within the more general framework of material happenings as expressed by thermodynamics.

Stable replicating systems operate according to the rules that govern replicating systems, as described earlier in this chapter, but that specific behaviour is not independent of the Second Law. Rather, it operates within the general constraints

‘Most chemists believe, as do I, that life emerged spontaneously from mixtures of molecules in the prebiotic Earth. How? I have no idea.’

alternative scientific view, panspermia, invokes the idea that life originated from beyond the earth and was transported in some fashion to the prebiotic earth.

it merely transplants the problem to some other unidentified cosmic location.

how did life emerge from non-life?

The historical aspect would seek to answer the how question—how did life emerge.

chemical events that transpired on the prebiotic earth—the particular chemical path followed, step by step, leading from inanimate materials through to simplest life.

The ahistorical aspect would address the more general why question: why would inanimate matter of any kind, regardless of its structural identity, follow a pathway of complexification in the biological direction, eventually leading to some simple life form?

Could the process, at least in principle, be induced in a range of different materials? What physicochemical principles

can we go a step further and postulate the existence of a ‘physical’ driving force that would have directed inanimate matter to complexify in the biological direction? That question, as phrased, rests on an additional presumption, that the emergence of life was not a purely random event, but one that was induced by established physicochemical forces.