What is Life?:How chemistry becomes biology (11 page)

I have described here the existence of a distinct kind of stability quite different from the regular stability with which we are more familiar, so given the existence of two kinds of stability, one might ask which is the preferred one, which stability is inherently the more ‘stable’? A definitive answer to the question is actually not possible—it’s the old apples and oranges problem. The two kinds of stabilities are not directly comparable and in fact one of them, dynamic kinetic stability, is only quantifiable in a very limited way. But intuitively we might suspect that static stability, the one based on a lack of reactivity, is inherently the preferred kind of stability, the one likely to be more enduring—wouldn’t it? Well, not necessarily! In examining the world around us we are led to a surprising conclusion. Mt. Everest, for example, a statically stable entity (ignoring tectonic movements), is thought by geologists to have existed for some 60 million years, so clearly static stability can be very substantial. But cyanobacteria (blue-green algae), a very
ancient life form, appear to have continuously populated the earth for several billion years, with little, if any morphological change. Biologists might argue over the period that they have remained unchanged, whether it is closer to 2.5 or 3.5 billion years, but there is no argument that cyanobacteria have been around for several billion years. Now that
is
stable! Of course, we are speaking here of a dynamically stable system—the cyanobacteria alive today are not the same ones that were alive several billion years ago. But through ongoing replication they have maintained a continual presence on this planet for an extraordinarily long period of time. Let us be clear: despite the dynamic character associated with replicating systems, their form of stability should not be underestimated; it is able to encompass time frames that cover a significant fraction of this planet’s 4.6 billion-year lifetime.

Our discussion till now has made clear that (static) thermodynamic stability and dynamic kinetic stability are applicable to different systems and are quite distinct in their nature. But the fact that there are two very different kinds of chemical stabilities has profound implications for both the physical and chemical characteristics of systems within each of the two classes. This is because the rules governing transformations for chemical systems belonging to the two different stability types are necessarily different. In effect there are
two
chemistries out there! One of the chemistries is just ‘regular’ or traditional chemistry, which has been studied for several centuries and is well understood—a mature science. The other is replicative chemistry, the chemistry of replicating systems. This other chemistry, part of a new area of chemistry recently named ‘systems chemistry’, is still in its infancy.
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Systematic study in the area was only initiated some twenty-five years ago
and many chemists remain unaware that such a field even exists. Let us now flesh out the nature of this ‘other chemistry’, why it comes about, what are some of its prime characteristics, and how this new field is providing the basis for the building of bridges between the sciences of chemistry and biology.

In 1989, Richard Dawkins alluded to a fundamental law of nature which applies to both the biological as well as the broader physicochemical world: the
survival of the most stable.
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Steve Grand, in his 2001 book,
Creation,
expressed it somewhat differently:
Things that persist, persist. Things that don’t, don’t
.
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This sounds like a tautology, and in some respects it is. But there is an important message present within that seemingly trite statement. Once it is (empirically) evident that matter is not immutable, that it is susceptible to chemical change, then it necessarily follows that matter will tend to be transformed from less persistent to more persistent forms, in other words,
from less stable to more stable.
Persistent forms don’t tend to change because they are… persistent. And, of course,
less
persistent things
do
tend to change because they are
less
persistent. So matter, by definition one could say, tends to become transformed from less persistent to more persistent forms, or couched in stability terms, from less stable to more stable forms. As a matter of fact, that is what chemical kinetics and thermodynamics is all about—being able to explain or, better still, predict the likely reactions of chemical systems in their search for more stable forms. And what is the central law that governs such transformations? The Second Law. A mixture of hydrogen and oxygen gases readily reacts
to give water because the hydrogen-oxygen gas mixture is unstable, whereas the water product is stable. When matter reacts chemically, it reacts so as to become transformed from thermodynamically
less
stable reactants into thermodynamically
more
stable products.

But what happens in the chemical world of replicators, in the world of replicating molecules, for example? What rule governs transformations within that world? Of course a replicating molecule may undergo chemical reactions in which it is converted into one or more
non-replicating
molecules. However, we are not concerned here with those kinds of reactions. They are covered by the rules governing chemical reactions generally. The reactions that are of special interest are those in which a replicating molecule (or set of molecules) is transformed into some
other
replicating molecule (or set of molecules). It is these reactions, which address the nature of replicating systems
as a class,
that we must further explore. As we will discover, it is this very special class of molecules that offers unique potentialities. And now to the essential point: 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.

That selection rule is in some sense an analogue of the Second Law, the selection rule in the regular chemical world. In both worlds chemical systems tend to become transformed into more stable ones, but as the two worlds are each governed by a different kind
of stability, the selection rule in each world is different—thermodynamic stability in the ‘regular’ chemical world, dynamic kinetic stability in the replicator world. As we will now see, the implications of those distinct selection rules are profound. But before we discuss those implications, is there any evidence for the distinctly different selection rule in the replicator world that is being proposed here? Yes, there is. Back to Sol Spiegelman and his remarkable RNA replication experiment conducted over forty years ago.

In describing Spiegelman’s landmark experiment earlier in this chapter, I neglected to tell the whole story. It is true that an RNA strand when mixed with its component building blocks (and added enzyme catalyst) undergoes a self-replication reaction. But something else takes place as well, something of considerable significance. Replication may on occasion occur imperfectly, in that the wrong nucleotide segment will attach to the template. For example, a C nucleotide, rather than an A nucleotide, will attach to a U segment on the template chain. 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. In fact the original sequence after some time may even disappear from solution! In other words, a process akin to 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. The replicating prowess of the short strand was so dramatic it was termed Spiegelman’s Monster!

Before continuing it is important to note that the evolutionary process observed by Spiegelman is chemical in essence, not biological. 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. While this is not the place to go into a detailed kinetic analysis of the competition between two replicating molecules, the bottom line is easy to state. When a number of different replicating molecules all compete for the common building blocks from which they are constructed, the faster replicators out-replicate the slower ones so that over time the slower replicators will tend to disappear. What effectively happens is that slower replicators are replaced by faster ones in precise agreement with the general selection rule for replicating entities that was specified above.

As a final point it is important to ask how the two stability kinds, static and dynamic kinetic, interrelate. The statement that the replicating world is governed by the drive toward greater dynamic kinetic stability, though correct, needs to be qualified, and that qualification can be expressed through the metaphor of Russian dolls. Although the replicative world is governed by an analogue of the Second Law, no physical or chemical system can avoid complying with the Second Law itself. That is the grand and comprehensive rule, the one governing
all
transformations in the material world. So how can two different laws operate simultaneously on the one
system? The answer is that the Second Law analogue governs replicating systems within the constraints of the Second Law itself, just like Russian dolls that fit one within the other. A simple example from everyday life may clarify the issue.

Your car breaks down and you ask your mechanic to explain the reason for that breakdown. If he mumbles something about the Second Law of Thermodynamics as the explanation for the breakdown, you’d be quite frustrated, even though his explanation was entirely correct. Correct, but quite unhelpful. The direction of all irreversible processes is governed by the Second Law, so whatever event caused your car to break down it was in a fundamental way governed by the operation of the Second Law. So why was the answer unsatisfactory? Because there are rules that govern car function—how engines operate—that sit within the more general framework of material happenings as expressed by thermodynamics. The Russian doll of engine function sits within the bigger thermodynamic doll. To fix your car you want to know what happened within the context of the smaller doll, the one that deals specifically with engine function. Did the fuel line become blocked or did the timing belt break? The Second Law, the more global explanation, though correct, is of no practical use. And so it is with replicating systems. 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 that the Second Law places on
all
material systems. There is no contradiction then between the two rules. The underlying message in the Russian doll metaphor is that we will be better able to understand reactions in the replicative world by considering the
rules that govern
that
world, rather than the more general thermodynamic principles that govern all material systems. Stating that the reactions of replicating molecules and biological evolution, in general, are governed by the Second Law is formally correct, but very much like saying that that is the reason your car broke down. Correct, but not particularly helpful!

Though this chapter on chemical stability and reactivity was chemical in its approach, we will subsequently see that it can provide the basis for our attempt to bridge between chemistry and biology. We will discover that biological terms, such as fitness, are directly related to chemical terms such as stability. But before we seek to understand the chemistry–biology connection in depth and to discover the relationship between chemical replicators and biological ones, let us consider the process which necessarily led to the transformation of chemistry into biology—the origin of life on earth—and see why that issue continues to remain stubbornly controversial. As I have already pointed out, if we want to understand what life is, we have to understand the essence, if not the detail, of the process by which it came about.

Mankind’s preoccupation with life and its origin can be traced back almost 3,000 years and it is not by chance that the opening lines of the first book of the Old Testament, Genesis, offers a biblical account of that extraordinary event. The narrative from there is long and convoluted, but we will take up the story from the early twentieth century, which is when the modern scientific dialogue commenced in earnest.

The origin of life problem is a tantalizingly difficult one. George Whitesides, the distinguished Harvard chemist recently expressed it in unusually frank terms: ‘Most chemists believe, as do I, that life emerged spontaneously from mixtures of molecules in the prebiotic Earth. How? I have no idea.’ That sums it up pretty well. In this chapter I will review this long-standing question to see where the debate currently stands and where the major problems lie. My approach is critical rather than comprehensive.
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