What is Life?:How chemistry becomes biology (13 page)

Fig. 4.
Tree of life based on ribosomal RNA sequence analysis showing three kingdoms of life—Bacteria, Archaea, and Eukarya.

In recent years the true significance of sequence analysis, even for established life forms, has been increasingly questioned. The problem initially arose in the 1990s when it became possible to carry out complete genomic (DNA) sequencing and not just sequencing based on RNA and protein. The troublesome finding was that the tree topology using the different molecular probes often differed significantly. One tree might suggest, for example, that species A is closely related to species B but not to C, whereas the other method might suggest that A is more closely related to C, and not to B. Clearly conflicting topologies cannot all be right. The primary explanation for this anomaly was quickly understood to be Horizontal Gene Transfer (HGT),
³⁵
the process in which an organism transfers genetic material to some organism other than one of its own offspring. HGT contrasts with traditional vertical gene transfer, whereby gene transfer takes place in the traditional fashion—from parent to offspring, the way heredity normally operates. The result is that the genealogical significance of the particular tree topology that is obtained cannot be entirely assured—the tree outline starts to blur.

For established life forms the extent of the problem is a subject of ongoing debate, but with 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. In fact, 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.
³⁶
This then suggests that the root of the universal tree of life, LUCA, may be something of an artefact which derives from forcing a tree representation on the sequencing data. If true, that statement has important consequences. It means that the nature, or even the very existence, of a discrete LUCA remains uncertain. That of course makes any phylogenetic extrapolation regarding pre-LUCA entities even more
questionable. After almost four decades of phylogenetic analyses the methodology has had to undergo significant reassessment. The tree of life, at least for archaea and bacteria, has been replaced by a web of life. A tree topology of course leads back to a trunk and to roots, but a web topology, unfortunately, does not lead anywhere; a web topology is not a useful source of historical information. The bottom line: when the significance of phylogenetic analyses of established life forms and the LUCA, in particular, are increasingly being questioned and revised, extracting useful phylogenetic information regarding
earlier
transitional life forms (pre-LUCA) seems to be, at least at present, a questionable endeavour.

We have discussed the palaeobiologic and phylogenetic tools as a means of obtaining historical information of early life on earth and found that they are unable to provide insights into the process by which inanimate matter was transformed into simple life. However, there is an additional approach to the historical question that potentially could provide useful information: assessing the kind of prebiotic chemistry that could have taken place on the earth, given prevailing prebiotic conditions. Could the study of prebiotic chemistry provide insights into life’s beginnings? Regrettably, the answer to that question has also not been encouraging. Despite considerable effort that has gone into exploring this line of thinking, the fruits of that labour have been meagre. Let us now look at the main contributions to that effort and consider why they have met with limited success.

It is clear that for life to have emerged on earth, the appropriate building blocks, from which all living systems are constituted, must
have been available. Accordingly, it seems reasonable to presume that some hints with regard to the origin of life could be revealed through analysis of the materials that might have been formed on the prebiotic earth. Though a 1924 paper entitled ‘The Origin of Life’ by Alexander Oparin offered some early ideas on the prebiotic formation of organic materials, the origin of life question was thrust into prominence with the landmark experiments of the American chemist, Stanley Miller.
³⁷
In these experiments 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. The prevailing thinking was that by conducting additional Miller-type experiments under presumed prebiotic conditions, the source of other key life components might be uncovered, thereby contributing to the resolution of the origin of life problem. Indeed, 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. For a period the road ostensibly leading to the origin of life began to look like a superhighway.

But not for long. Dissenting voices quickly arose. Just where on the earth did life’s emergence take place? 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.
³⁹
Differences don’t get much greater than that! But then questions regarding the composition of the prebiotic atmosphere arose. Was the prebiotic atmosphere in fact reducing, as initially proposed, or, on the basis of more recent data, was it neutral, containing mainly carbon dioxide, nitrogen, and water? No broad agreement on any of these fundamental questions seems to have been reached.

Thus the initial excitement induced by Miller’s experiments was gradually replaced by a phase in which a range of competing, mutually incompatible proposals were offered. Optimism gave way to lack of coherence and uncertainty. In fact, the only point on which the different mechanistic proposals for the emergence of life
were
in agreement was that life on earth
did
emerge some 4 billion years ago from inanimate materials present on the prebiotic earth. It is true that the richness of chemistry associated with prebiotic styled experiments did lead to the discovery of a range of novel chemical reactions and opened up alternative ways of thinking about the topic. However the considerable effort that was put into that endeavour seemed to have been accompanied by a questionable way of reasoning. In simplest terms, a general thesis that formed the basis for much of the discussion on prebiotic chemistry took shape, namely, that from the study of chemical reactions under supposed prebiotic conditions, it is possible to outline pathways that could
have led to the emergence of life. In retrospect that thesis now appears to be highly problematic. Seeking out the historical conditions for life’s beginnings on the prebiotic earth has not contributed significantly to resolving the origin of life problem.

There are several problems with the ‘prebiotic chemistry’ approach. First, the absence of reliable information regarding conditions on the prebiotic earth, certainly with respect to any specific location, has significant consequences. If we want to specify the nature of reactions that could, or could not, have occurred at some particular site on the prebiotic earth, the available materials and the corresponding reaction conditions at that site must be specified. But since neither the available materials nor the reaction conditions are known, almost nothing can be said with any degree of confidence.

To illustrate the depth of the problem, consider for example the expression ‘conditions on today’s earth’, an expression presumably more definitive than the corresponding term ‘conditions on the prebiotic earth’. But what does ‘conditions on today’s earth’ actually signify? Are we speaking of the conditions within an erupting volcano, under the arctic ice shelf, at the bottom of the ocean, in a hydrothermal vent, in the hot sands of the Sahara desert, in a freshwater lagoon, or in any number of other totally different locations? The term raises considerable uncertainty even though we
can
specify with some precision the conditions at any given location. But when we speak of conditions on the prebiotic earth, and do so in a most general way, the uncertainty takes on an extra dimension. Not only don’t we know
where
on earth particular pre-biotic events took place, but we don’t really know the actual conditions at any of those prebiotic locations. And to make things more difficult, the study of physical organic chemistry teaches us
that reaction paths and reaction mechanisms can be quite sensitive to reaction conditions, so any proposals as to what may or may not have taken place at some point on the prebiotic earth can only be classified as highly speculative.

Speculation on these questions is also methodologically problematic since it is unlikely that any scenario is falsifiable in practice. The number of plausible scenarios would only be limited by the creative efforts of those chemists applying themselves to the question. Needless to say the lack of falsifiability necessarily undermines the utility and significance of any particular proposal. As Leslie Orgel, the eminent British chemist and leading origin of life researcher, once put it: ‘Just wait a few years and conditions on the primitive Earth will change again.’ A cynic might argue that here we have the ideal research area. One could safely publish in the field, secure in the knowledge that no one is ever likely to prove you wrong!

There is a second problem, no less fundamental, with the presumption of particular prebiotic conditions. Even if prebiotic conditions could be specified with some precision, it has been frequently assumed that the knowledge of such conditions would enable us to specify not only what reactions
could
have taken place, but also what reactions
could not
have taken place. That presumption has in fact been used to argue against one of the main origin of life scenarios—the existence of an RNA-world as a transitional period on the way to simplest cellular life. Since long chain RNA molecules are formed from their component building blocks—RNA nucleotides—the RNA-world scenario crucially depends on the appearance on the prebiotic earth of those nucleotides. The argument offered was essentially the following: if, 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. How many decades of effort by gifted chemists are required before the conclusion is justified? Two, three, maybe five? And how gifted do the chemists have to be? As discussed above in some detail, it is simply unreasonable to conclude that prebiotic conditions at
every
location on the early earth would have precluded the emergence of nucleotides when the available materials and reaction conditions at
any
of the possible locations remains unknown.

In any case, the fallacy was laid bare quite recently by the imaginative British chemist John Sutherland when he did the ‘impossible’. 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, by utilizing a novel synthetic strategy quite different from the conventional one attempted by earlier researchers.
⁴⁰
One can only fantasize as to how many other feasible ‘prebiotic syntheses’ of nucleotides or any other key building block might in principle exist. Shouldn’t nature also be allowed the prerogative of ‘thinking out of the box’? The conclusion is clear: though one can safely conclude 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. The comment
by a pioneer in the origin of life area, the venerable Peter Schuster, regarding prebiotic chemistry is particularly apt: ‘Never say never!’ We will return to the possible role of RNA on the prebiotic earth in
chapter 8
, as the fortuitous emergence of a molecule capable of self-replication is a central theme in the origin of life debate.

The above two arguments have demonstrated the inherent difficulties in the prebiotic chemistry approach to the origin of life. However it turns out that the problems run even deeper. We argued above that seeking to discover the prebiotic conditions that could have led to the emergence of biologically relevant materials is problematic. But behind that endeavour lies an unstated assumption, namely, that if some convincing explanation for the availability of the key biomolecules from which all living things are composed—sugars, bases, nucleotides, amino acids, lipids, etc.—can be found, then a major step toward resolving the origin of life problem will have been taken. Unfortunately that assumption is also questionable. Even if all the experiments in prebiotic chemistry had been carried out with total success, thereby fulfilling prebiotic chemists’ wildest dreams, the origin of life riddle would still be a riddle, because the true problem with regard to the origin of life goes beyond the question of how life’s building blocks appeared on the prebiotic earth. A deeper problem lies elsewhere.