by Pross, Addy
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.
Prebiotic chemistry
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 spontaneousl
y 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.
Consider, you establish a group of leading biochemists, synthetic chemists, molecular biologists, and you ask them to create a simple living system in their laboratory. No restrictions of any kind, no chemical limitations, none of the constraints that would have necessarily accompanied conditions on the prebiotic earth. And no funding limitations either! Offer them whatever materials they would like in any combination they would like—DNA and RNA oligomers, lipids, assorted proteins, sugars, any catalyst they would want, and, of course, any instrumentation they might require. Create for them any reaction conditions needed to carry out their experiments, prebiotic or otherwise. If they request simulated conditions resembling those within a hydrothermal vent, no problem. Clay surfaces? That one’s easy. But the honest response? Most would not really know where to start!
Certainly, a number of audacious scientists, such as Jack Szostak, the Nobel geneticist at the Harvard Medical School, and Pier Luigi Luisi, the venerable Italian chemist, have taken some tentative steps toward that ambitious goal,41 but for reasons we will discuss in chapter 8, the obstacles in reaching the target remain formidable. The problem of how life emerged on the prebiotic earth is not just about what materials were available and identifying the reaction conditions at the time, because even the very best chemists without any resource limitations would not really be sure how to proceed. And the problem does not stem from the fact that one particular step or other in the recipe for life is especially difficult and still technically out of reach. The problem is more fundamental. The problem is there is still no coherent recipe. As we noted earlier, we don’t yet adequately understand what life is, so how can one go about making something that we do not as yet fully understand? So, in a fundamental sense, the efforts to uncover prebiotic-type chemistry, while of considerable interest in their own right, were never likely, in themselves, to lead us to the ultimate goal—understanding how life on earth emerged.
In fact we would go so far as to say that seeking historical information regarding the emergence of life on earth is a honey trap—seductively appealing, beckoning both the novice and the experienced researcher, but one that is unlikely to yield genuine insights with respect to the question it poses. More significantly however, historical evidence alone, even if it were to become available, would not resolve the problem. The real challenge is to decipher the ahistorical principles behind the emergence of life, i.e., to understand why matter of any kind would tend to complexify in the biological direction. It is this ahistorical question, independent of time and place, which lies at the heart of the origin of life problem. In order to resolve the origin of life mystery, and it is a mystery, we need an understanding of the physicochemical processes that would have converted inanimate matter of whatever kind into a chemical system that we would categorize as living. That is the issue that kept the great twentieth-century physicists awake at night, not prevailing uncertainties with regard to the composition of the prebiotic atmosphere or the feasibility of synthesizing nucleotides under prebiotic conditions, and the like. 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?
Of course, once the general principles that govern such transformations have been characterized, there is still no guarantee that the historical question can then be resolved. After all, we are talking about particular events that took place on the earth some 4 billion years ago, so our ability to uncover the nature of those historical events is limited in the extreme. However, if and when that ahistorical question is resolved, the problem of how life on earth emerged on the prebiotic earth would take on a totally different aspect. Being a historical question the answer might remain unknown, but the issue would no longer be a mystery in the same way that it is now. Importantly, based on the above discussion, 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. Richard Feynman, the iconic Nobel physicist, once said: ‘What I cannot create, I do not understand.’ This truism might be usefully turned around: What I do not understand, I cannot create.
I have described in some detail the limitations in tackling the origin of life problem through its historical aspect, so let us now consider how the problem may be tackled through its ahistorical aspect. And it is here that we’ll find room for greater optimism. Ahistorical principles are as relevant today as they were 4 billion years ago—the rules of physics and chemistry do not change over time. So rather than speculate as to what might have transpired on the prebiotic earth, let us investigate what does take place on today’s earth. Let us study and experiment with chemical systems of the right kind, in order to glean information and obtain insight into this key question.
As we mentioned in chapter 4, systems chemistry deals with the class of simple replicating molecules and the networks that they create. That area of study, still in its infancy, has
already revealed that reactivity patterns observed in such systems are quite different from those we find in ‘regular’ chemistry, and may provide insight into the kind of chemical processes that led to the emergence of life. In fact the switch in emphasis from historical to ahistorical leads us directly to an issue that has been central to the origin of life debate for several decades. Since all living systems are characterized by possessing a metabolism and the ability to reproduce themselves, which of these two capabilities came first—replication or metabolism? At first the question might sound historical in its approach—which came first? But the nature of these two capabilities may be such that chemical logic could dictate the natural order to be expected, and, as a consequence, could provide insight into the process of emergence. As we will see, the implications of the ‘metabolism first—replication first’ dichotomy are significant because 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.