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

by Addy Pross

Notice that the answer to the ‘why’ question is formulated in terms of a general law, independent of the specific location of the boulder, the nature of the terrain, etc.

For example, understanding the ahistorical aspect—the nature of the physical force responsible for boulder motion—would greatly assist in answering the historical question, that of boulder trajectory. Indeed, due to our knowledge of gravity we can safely

if we want to address the historical origin of life question in its particulars, namely, to specify the starting materials and the particular set of reaction steps that led from those materials to early life forms, then knowing the general principles that govern the conversion of relatively simple molecular systems into the complex systems of life would be of considerable value. It would suggest the kinds of historical evidence we should be seeking. And vice versa, knowing the reactions that led to the conversion of inanimate matter into animate matter would greatly assist in uncovering the general principles that would have governed such a remarkable transformation.

microfossil remains of ancient microorganisms, and most recent findings date that early life at about 3.4 billion years old.33 In any case all of these fossil findings point to relatively advanced cellular life, and therefore do not throw light on the earlier process of abiogenesis.

extinct. So start from any branch end, follow it back, and you will uncover the entire evolutionary record of that particular species.

the closer two species happen to be in evolutionary terms, the greater the similarity in the sequence of any biomolecule shared by the two species is likely to be. Carry out that comparative study for a large number of species and the genealogical relationship between different life forms, as expressed in a tree structure, can be established.

1970s, primarily due to the pioneering sequence analysis work of Carl Woese, it was discovered that archaea are more closely related to eukaryotic cells (those making up you and me) than to bacterial cells! As a result, the two seemingly closely related prokaryotic life forms were relegated to distinct and separate kingdoms.

Horizontal Gene Transfer (HGT),35 the process in which an organism transfers genetic material to some organism other than one of its own offspring.

regard to the origin of life issue the news is worse. The problem is that the further back one follows the branches of the tree, the greater the impact of HGT seems to be.

Carl Woese, whose life work focused on such phylogenetic analysis, argues that early cellular organization would have been loosely connected and modular, that evolution would have been communal, not individual, so that such entities would not have even had stable genealogical records.

Miller, then a graduate student under the direction of Harold Urey, a Nobel chemist at the University of Chicago, took a mixture of the four gaseous components thought at the time to be the main constituents of the prebiotic atmosphere—hydrogen, ammonia, methane, and water vapour, and simulated the effect of primordial lightning by passing an electrical discharge through the mixture. The result was dramatic. A range of organic materials, including a number of amino acids, were found to have been formed. Since amino acids are the building blocks of proteins, proteins being a key component of all living systems, a new area of study was established—the field of prebiotic chemistry, a field that quickly became a focus of considerable scientific interest.

within a few years another group of organic substances, the organic bases, which constitute a key component of all nucleic acids, were also shown to be readily synthesized from available simpler materials, under what were considered to be likely prebiotic conditions.

The initially preferred location, within a so-called ‘prebiotic soup’, was questioned for a variety of reasons and the hunt for creative alternatives quickly expanded. Two of the more prominent ones were the suggestion that life originated in hydrothermal vents deep under the sea,38 while another proposed that life was initiated on clay surfaces.

despite several decades of effort, gifted chemists were unable to synthesize RNA nucleotides under presumed prebiotic conditions, then it can be safely concluded that such nucleotides could not have spontaneously appeared on the earth.

Here the flawed logic is easily exposed. We simply cannot rule out the possibility of prebiotic RNA nucleotides emerging spontaneously because, as the old saying goes: absence of evidence does not constitute evidence for absence.

John Sutherland was able to synthesize an RNA nucleotide from so-called prebiotic starting materials and the breakthrough came about by his thinking out of the box,

from experimental results which chemical reactions are possible, it is logically unsound to conclude what reactions are not possible, what could not have taken place, particularly over a time span of hundreds of millions of years, and under effectively unknown reaction conditions.

What laws of physics and chemistry could explain the emergence of highly complex, dynamic, teleonomic, and far-from-equilibrium chemical systems that we term life?

I am of the view that attempting to seek out life’s molecular beginnings before we have adequately clarified the physicochemical principles that underlie biological complexification is tantamount to attempting to assemble a watch from its component parts—springs, cogs, wheels, etc.—without understanding the principles that govern watch function.

which of these two capabilities came first—replication or metabolism?

they directly impact on all three questions that make up the triangle of holistic understanding, namely, what is life, how did it emerge, and how would one make it.

In the context of the origin of life question, ‘metabolism first’ mechanisms presume that some relatively simple autocatalytic chemical cycle, a forerunner of the complex metabolic cycles found in extant life, emerged prior to the appearance of an oligomer-based genomic system.

The ‘replication first’ school also views life as having been initiated by the emergence of an autocatalytic system, but in this case one based on a template-like oligomeric replicator, such as RNA

So the ‘metabolism first—replication first’ debate may also be expressed as which came first, the spontaneous formation of a holistically autocatalytic chemical cycle, or the emergence of some template molecular replicator?

Does the essence of life derive from the sequential nature of certain oligomeric molecules, or from the complexity associated with holistic autocatalysis?

Let us recall what the ‘replication first’ scenario actually proposes. It rests on the idea that once some self-replicating entity happened to emerge, it then proceeded to complexify until it became transformed into some minimal life form. The difficulty with that proposal is that the simplest living system is a highly organized far-from-equilibrium system, which needs to constantly consume energy in order to maintain that far-from-equilibrium state. In other words for a replicating molecule to have complexified into a simple living system would have meant that instead of reacting to yield thermodynamically more stable products, it ended up becoming a highly complex thermodynamically unstable system.

was it a fantastically improbable accident—a freak occurrence that would almost certainly never be repeated—or was life’s emergence inevitable given the existing laws of physics and chemistry.

Darwin’s monumental achievement was, of course, in providing biology with a physical foundation, thereby successfully transplanting biology from the supernatural world into the natural world.

‘living systems have special properties which arise primarily not from the substances of the system, but from their special organizational manner.’49 It is the organization of life rather than the stuff of life that makes life the unique phenomenon that it is.

once some unexplained phenomenon is classified as an ‘emergent property’, it could be thought of as explained, that no further consideration of the phenomenon is required. How else to understand the almost total lack of interest that the scientific community has shown in the physicochemical basis for teleonomy, that most remarkable of emergent properties?

the body of water immediately responds to this unstable situation—it begins to flow down the drain in order to lower its potential energy and reach a new equilibrium state. But in doing so something special takes place—the body of water generates a structure, a vortex. The non-equilibrium state has spontaneously generated a non-equilibrium structure.

some similarity exists between dissipative structures and living cells.

there is no evidence that the laws of non-equilibrium thermodynamics apply to biological systems in a non-trivial fashion.

the fact that complex systems may result from the operation of relatively simple rules is informative in itself.

If we think of biology as the field of endeavour that studies those highly complex chemical systems capable of replication or reproduction, then systems chemistry (or at least central aspects of it) deals with relatively simple chemical systems that also possess that special characteristic of self-replication, and in doing so attempts to fill the chasm-like void that continues to separate chemistry and biology.

If you want to figure out what an airplane is, and the principles governing its flight, you’d be much better off examining an earlier simpler airplane, say the Wright brothers’ 1903 prototype or some other simple equivalent, where the number of components is a tiny fraction of that in the Boeing, and one in which every component plays an important, if not critical role in enabling that entity to become airborne.

that’s where systems chemistry comes in—by examining the workings of simple replicating systems and the networks they generate, we are attempting to do the equivalent of examining the Wright brothers’ airplane rather than a Boeing 747.

The so-called two-stage process is not two-stage at all. It is really just one single continuous process. If true that statement has quite profound consequences. First it must mean that hidden within Darwin’s theory of evolution—biological in formulation and application—a more fundamental, broader principle is at work, which must necessarily incorporate prebiotic systems, which by definition would be classified as non-living. In this chapter, I will attempt to justify the one-process assumption and explore some of its implications.

A key ecological principle, termed the competitive exclusion principle, states: ‘Complete competitors cannot exist’ or, expressed in its positive form: ‘Ecological differentiation is the necessary condition for coexistence’.

the competitive exclusion principle.

when the two RNA molecules were allowed to replicate and evolve in the presence of not one, but five different substrates, the two RNAs were able to coexist, but in an unexpected way. Initially the two RNA molecules utilized all five substrates in varying degrees in order to replicate. After all, all five were present and therefore all five could be utilized to some extent. But here is the punch line: over time each RNA molecule evolved so as to optimize its replicative ability with respect to different substrates. RNA-1 evolved so as to optimize its replicative ability with just one of the five substrates, while RNA-2 evolved so as to optimize its replicative ability with another of those five substrates. As a result, the two RNAs were now able to coexist. In this beautifully designed experiment, which explored the characteristics of competing molecular replicators, the two RNA molecules were found to mimic the behaviour of Darwin’s finches precisely!

The earliest life forms that emerged, perhaps 4 billion years ago, were simple cells, prokaryotes (meaning that the cells lack a nucleus and other organelles). But after a further 2 billion years of evolution, eukaryotic cells emerged, in which membrane-bound organelles, including the cell nucleus, can be found. And some 600 million years ago another evolutionary transition involving further complexification took place, the one in which multicell organisms—plants and animals—appeared.

there is unambiguous evidence for a process of increasing complexity.

both chemical and biological phases of Fig. 6 involved a process of continual complexification.

the difficulty in getting so-called replicating molecules to replicate when no biological materials are added to ‘help’ things move along, has been viewed as one of the stronger arguments against a replication-first scenario for the emergence of life.

switched from a single replicating RNA molecule to a two-molecule system composed of two discrete RNA molecules that had been obtained in a careful selection process, then replication proceeded rapidly—the initial sample doubled in quantity in just one hour—and replication could be sustained indefinitely, provided the building blocks were available. How come? Why the difference?

one RNA molecule was inducing the formation of the other, while the other molecule was inducing the formation of the first.

cross-catalysis—each RNA molecule was catalysing the formation of the other.

what one simple replicating entity could only do inefficiently, a more complex one was able to do more efficiently.