Problems with experiments

One difficulty is that the great majority of experiments connected to one or other aspect of the origin of life do not actually work. Not surprisingly, such results are seldom reported. This is not any sort of dishonesty; it is simply that in exploring prebiotic chemistry most avenues are going to prove to be dead ends, tracks leading nowhere. Well, that is quite typical in science, yet in the field of the origin of life this problem indicates some more pervasive difficulties. An illuminating example is provided by Anthony Keefe and Stanley Miller,18 who consider the crucial role of the element phosphorus. As is well known to biologists, phosphates play a key role in the biochemistry of all organisms, perhaps most notably by the agency of the compound ATP (adenosine triphosphate), which is usually referred to as the 'currency' for energy transfer. This is on the basis of its ability to store substantial amounts of energy, specifically in the branch of the molecule that contains the phosphoanhydride bonds. It seems almost certain that before the 'invention' of ATP there must have been some sort of prebiotic phosphate compound capable of a similar, if less efficient, function. It had been long appreciated that the production of such compounds was fraught with difficulties, at least if the experiments were to be conducted in a believable prebiotic milieu. Keefe and Miller therefore embarked on an extensive series of experiments that took as their starting points a credible range of chemicals that one might reasonably expect to exist on the early Earth. The net result of this programme was effectively a catalogue of disasters, and although there were local successes Keefe and Miller were forced to conclude that none of the new processes they had investigated would be 'sufficiently robust to have been of importance in the prebiotic ocean'.19

One of the problems Keefe and Miller encountered was that in most cases the yields of the favoured compounds were very low. This is one of the recurrent features of such experiments into the origin of life: again and again a compound that is believed to hold a key role in some significant path of biochemistry is indeed synthesized, but typically the reactions are highly inefficient and the quantities produced are quite negligible. To be sure, one or more agencies of distillation or concentration may be invoked, but unless life itself is asked to give a helping hand - defeating, of course, the purpose of the exercise -then the mechanisms employed are highly artificial, if not contrived. There is also a flip side to the production of potentially important pre-biotic molecules. Not only are the yields often disappointingly low, even minuscule, but typically (and unsurprisingly) the experiments produce a wide range of other chemicals that seemingly have no relevance to the origin of life. In some instances a substantial quantity of the organic material synthesized forms a tar-like 'gunk', reminiscent of the heterogeneous 'goo' found in the carbonaceous meteorites (Chapter 3).

Many of the difficulties just referred to are exemplified by what has come to be known as the 'ribose problem'. Ribose is a sugar, one of a large group of molecules related to the molecular family known as aldopentoses. In its right-handed, or dextral, form it is one of the key ingredients of life, most notably as a key component of the backbone of the genetic code, namely deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Given this crucial role, it is hardly surprising that the successful laboratory synthesis of ribose is a prime objective for understanding the origin of life. The starting point is formaldehyde, a simple molecule (H2CO), which is readily synthesized abiotically.20 Starting with formaldehyde, the next step is to engineer a process that will lead to a polymerization, that is, a stringing together of simple molecules, whereby more complex sugars can be formed. In certain circumstances one of these should be ribose.

So what is the 'ribose problem'? In a paper reviewing this area Robert Shapiro casts a withering eye on a number of earlier experiments in which success was claimed.21 In discussing one proposed pathway Shapiro bluntly remarks that the investigators are to be congratulated for their 'vivid use of imagination'.22 Among the various procedures that can be adopted, particular attention has been paid to what is called the formose reaction.23 This was first identified by a chemist, A. M. Butlerov, and is effectively concerned with the way in which complex compounds can be produced from the polymerization of formaldehyde under certain conditions. The limits within which this reaction operates are at least broadly consistent with what we

14 16 18 20 22 24 26 min figure 4.1 The 'ribose problem' exemplified. The graph (a gas chromatograph) shows the many products of the formose reaction, of which ribose - an essential component of DNA - is marked by peak 8. Such reactions, with a plethora of compounds, are the norm in prebiotic reactions, raising the question as to how separation and sufficient abundance of key compounds, such as ribose, was achieved. (Reprinted from Journal of Chromatography, vol. 244, P. Decker, H. Schweer, and R. Pohlmann, X. Identification of formose sugars, presumably prebiotic metabolites, using capillary gas chromatography/gas chromatography-mass spectrometry of n-butoxime trifluroacetates on O/V-225, pp. 281291, fig. 11.5. Copyright 1982, with permission from Elsevier Science.)

14 16 18 20 22 24 26 min figure 4.1 The 'ribose problem' exemplified. The graph (a gas chromatograph) shows the many products of the formose reaction, of which ribose - an essential component of DNA - is marked by peak 8. Such reactions, with a plethora of compounds, are the norm in prebiotic reactions, raising the question as to how separation and sufficient abundance of key compounds, such as ribose, was achieved. (Reprinted from Journal of Chromatography, vol. 244, P. Decker, H. Schweer, and R. Pohlmann, X. Identification of formose sugars, presumably prebiotic metabolites, using capillary gas chromatography/gas chromatography-mass spectrometry of n-butoxime trifluroacetates on O/V-225, pp. 281291, fig. 11.5. Copyright 1982, with permission from Elsevier Science.)

might expect on the early Earth, and indeed ribose is produced. But there is a snag: the yields are very low and the formose reactions produce a disturbingly large array of other compounds (Fig. 4.1). To compound the difficulties the ribose is rather unstable24 and degradation is particularly rapid if the solution becomes more alkaline. It is, of course, possible to tinker with the reaction to engender a greater degree of selectivity, but unfortunately this does not in itself boost ribose production. So we seem to have been led into an impasse. Nothing daunted, chemists have devised reaction pathways that can produce reasonable quantities of ribose,25 but the sheer complexity of the process and the careful manipulation of the many steps during the reaction make one wonder about its applicability to the origin of life.

A key element in the hunt for chemical pathways that might be relevant to prebiotic evolution is the search for natural catalysts that could not only accelerate the reactions but ideally could also impose a degree of specificity that might circumvent the problem of producing a cocktail of molecules, if not more goo. Perhaps this is the way to crack the ribose problem? G. Zubay26 tackled this question by looking at a wide array of potential catalysts that might direct the formose reaction in favour of particular sugars, including ribose. On his own admission this work was in part spurred on by the disappointment and frustration experienced in investigating whether widely available compounds such as calcium or magnesium hydroxides could act as catalysts. He found that they could not, but a search among other potentially suitable catalytic agents was equally futile, with the single exception of lead. This element certainly occurs in natural compounds such as the sulphide mineral galena, but Zubay himself was cautious as he added, 'we have pondered the legitimacy of lead as a prebiotic catalyst.'27

The most obvious way forward from such an apparent impasse is to find a viable precursor that is chemically simpler and, ideally, easier to synthesize. This is an important and more general point. If such a stage could be identified, it might even begin to show how nascent life, or its molecular antecedents, began to exert its strange yet characteristic specificity, its ability to select the one-in-a-million chemicals, by metaphorically dipping into the organic 'soup' and selecting any molecule that improves, be it ever so slightly, one or other biological process. Perhaps we should stop worrying about ribose, and look towards a more believable predecessor. Such might be the case with a compound known as a-threofuranosyl. This can be derived from a sugar (threose) with only four atoms (i.e. tetrose) and thus is simpler than ribose and perhaps easier to synthesize. Of equal significance is that a-threofuranosyl can be used in the building of a short molecular strand that is directly analogous to DNA (and RNA). This molecule, referred to as TNA (T for 'threo'), can form a double strand (a duplex), and, rather remarkably, can also pair with RNA and DNA. TNA could thus, at least potentially, be capable of replication, and thereby act as a genetic code.28 If so, this could obviously a very important step forward, but it raises two general problems. It is all very well to by-pass the difficulty of making ribose, but we need to ask whether the pathways of threose sugar synthesis (and those of the other component molecules of TNA) can themselves be reconstructed in a credible prebiotic milieu. The sequence of steps undertaken in this laboratory investigation is certainly very far removed from any 'warm, little pond'. The second problem is that while life must have originated in a series of step-like processes, as one moves to ever simpler compounds, so the real difficulty, that of bridging the gap between complex organic chemistry and any sort of functioning system we choose to call living, actually grows.

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