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Synthetic Biology and ‘Kon-Tiki’ Experiments

December 16, 2012

In this post, we change tack from those of the past few months and return to a theme raised previously (Posts of 30th May, 7th June, and 20th June 2011) which centers on synthetic biology. Here the power of future synthetic biological science will be highlighted by considering a potential application of it towards the analysis of ancient evolutionary pathways. At the same time, exploration of this theme has certain interesting implications concerning the accomplishments that natural biological evolving systems can and cannot achieve.

 The Kon-Tiki Expedition and Its Goals

The central theme of this post, which ultimately concerns the future of synthetic biology, is approached by means of an analogy. As a tool of thought, the stratagem of analogy-making should not be trivialized. Indeed, some opinion elevates it into a premier position in cognitive processes, without which progressive complex thinking would be stymied. At the heart of any analogy is cognitive ‘chunking’, where small concepts are joined together into successively bigger ones, to facilitate the manipulation of increasingly complex mental structures. (By this kind of analysis, ‘chunking’ itself thus necessarily involves a degree of chunking in order for it to emerge as a coherent thought).

The analogy to be made in this context comes from science itself, but within a very different and necessarily speculative field, which might optimistically be termed ‘experimental archaeology’. In 1947 the Norwegian adventurer and ethnographer Thor Heyerdahl led an expedition on a balsa raft from Peru in a westward direction across the Pacific to the Tuamoto archipelago, a string of islands among the very many which were long ago colonized by the Polynesians. Heyerdahl believed that these bold seafarers originated from South America and spread westwards, rather than eastwards from an Asian origin as usually thought. His ‘Kon-Tiki’ expedition was a grand adventure and a great story, and it directly proved that it was indeed possible for people to build a raft with stone-age technology and float across the Pacific from South America to Polynesia in a westerly direction. Later expeditions led by Vital Alsar even extended the demonstrable rafting range across the entire Pacific (the La Balsa and Las Balsas expeditions in 1970 and 1973, respectively). But impressive as these feats were, in themselves they had no bearing on how human colonization of the Pacific actually happened.

Genetic, linguistic and cultural lines of evidence converge on the conclusion that all Polynesian settlements have resulted from migrations radiating in a general eastward direction across the Pacific. It is ultimately Asia, rather than South America, from which the direct ancestors of Polynesians originally derive. Accordingly, the vast majority of researchers in this field reject the central tenet of  Heyerdahl’s hypothesis of colonization in the opposite direction by South American peoples. This was so even in 1947, and has only been reinforced across the intervening decades.  What Heyerdahl and his La Balsa successors showed is evidence of possibility. Their daring feats demonstrated that determined human beings, armed with only a low level of seafaring technology, could in principle accomplish voyages across even the greatest ocean of this planet. But evidence of possibility is not evidence of occurrence, and hypotheses, however logically appealing and dear to the hearts of those who propose them, must inevitably bow before the weight of factual evidence.

Yet the complete story may well be more complex. Genetic and carbon-dating evidence has been proffered suggesting that chickens found their way into domestic use by South Americans through the agency of Polynesians, and if true would prove that Polynesian sailors ranged beyond Easter Island onto the western coast of South America. Other data have nevertheless challenged this study, and the proposal remains controversial and unproven. Another item suggestive of South American interaction is the origin of the sweet potato grown for food in some Polynesian societies, but this too remains controversial. Since Polynesians indisputably did reach the remote Easter Island, the possibility of Polynesian pre-Columbian communication with South America is hardly an absurd proposition in itself. But this is obviously a different matter to suggesting that such interactions originated in the reverse direction from South America.

In any case, applying the history of the Kon-Tiki expedition (and its like) as an analogy for other kinds of scientific investigation leads to an operational definition for the present post: A ‘Kon-Tiki’ scientific experiment is here defined as a scientific endeavor which attempts to demonstrate the inherent feasibility of a proposed past event, system, or process (necessarily historical or evolutionary) by re-creating the substance of the item of interest. Of course, if the analogy with Heyerdahl’s expedition was taken to its maximal extent, a ‘Kon-Tiki’ experiment would verify feasibility but ultimately be discredited as representing any true recapitulation of an actual historical or evolutionary pathway. Here the operational definition accordingly refers only to the ‘verification of feasibility’ aspect of a ‘Kon-Tiki’ test. In other words, any generic successful ‘Kon-Tiki’ experiment by the definition of this post proves feasibility; it may or may not be compatible with other lines of evidence obtained independently. Following on from this, it is important to note that there is nothing inherently negative about a ‘Kon-Tiki’ investigation in its own right. A successful demonstration of the feasibility of a system or process can be very powerful, and (depending on the circumstances) may provide important evidence favoring a specific hypothesis which accounts for an evolutionary development.

While positive ‘Kon-Tiki’ data is not of proof of past events, in combination with other information it may become compelling (a point which is considered further below).

But on the other hand, failure of a ‘Kon-Tiki’ test of any description proves nothing. Had Heyerdahl and his friends failed to reach Polynesia, it could not be used as evidence that oceanic raft voyages by early South Americans were impossible. (Here, of course, we are only considering the rafting possibility itself, in isolation from the weight of evidence which favors eastward Pacific colonization). And the same principle would apply even if the subsequent La Balsa expeditions had also failed in their objectives. Naturally, if a dozen succeeding adventurers all had their rafts sink separately in the eastern Pacific, the likelihood that ancient South Americans could have succeeded where they failed would seem vanishingly small. Yet the possibility could not be formally excluded that conditions in the past were significantly different in some crucial manner which favored success: for example, a change in oceanic winds or currents. Thus, only positive ‘Kon-Tiki’ results can be taken any further.

 ‘Kon-Tiki’  Synthetic Biological Experiments

An early and famous experiment which has ‘Kon-Tiki’ aspects was published by Stanley Miller in 1953. The ultimate aim of this work was nothing less than an understanding of the origin of life, approached by designing experimental conditions such that they resembled what was believed to correspond to conditions on the prebiotic Earth in those times of the remote past. A mixture of water vapor, methane, ammonia, and hydrogen was subjected to a heat source and continual electrical spark discharges (simulating lightning), and after several weeks, the contents of the reaction flask proved to harbor many of the amino acids found as constituents of proteins. So this experiment has a ‘Kon-Tiki’ flavor in the sense that it tested the feasibility of a proposition (that organic building blocks could arise in prebiotic conditions) and used assumptions as to what the initial starting state should be (the above gaseous mixture). To relate the latter starting-point issue to the original Kon-Tiki and other rafting expeditions, Heyerdahl and colleagues made reasonable assumptions as to the level of technology available to early pre-Colombian South Americans. In fact, in this respect the rafting ‘experiments’ were probably on safer ground than Miller’s work, since the nature of the early prebiotic atmosphere may have contained considerably more nitrogen and carbon dioxide than Miller (and his supervisor Harold Urey) assumed.

But for present purposes, the intention is to relate ‘Kon-Tiki’ experimentation with what might be achieved in the relatively near future through powerful applications of synthetic biology. Indeed, it can be proposed that it is precisely the anticipated advanced state of synthetic biology during this century which will really enable ‘Kon-Tiki’ experiments to come into their own. In a previous post (of 20th June 2011) entitled ‘Synthetic Life Part III – Experimental ‘Dark Biology’, a number of ambitious future synthetic biological projects were listed. With that in mind, it’s time to consider that there are different levels at which the analogy can be made between the formal goals of the Kon-Tiki expedition and biological projects, which are noted in the Table below.


Table: Different levels of analogizing biological experiments to ‘Kon-Tiki’ investigations. In Type 1, the match with the Kon-Tiki approach is closest, corresponding to : (1) Making the best possible assumption about a previous biological or historical state based on available information; (2) Formulating a hypothesis to account for a system or process which occurred during the early conditions of (1); (3) Constructing a system or process in order to assess whether hypothesis (2) is possible at least in principle; and (4) Defining in advance criteria for a successful test as in (3). This matching occurs when experimentation is specifically designed to assess the possibility of a past hypothesized state. The examples of Type 1 also have the characteristic of having been completed, or are actively under current development. On the other hand, it is abundantly clear that synthetic biology can proceed far beyond merely attempting to recapitulate postulated states in early molecular evolution. Type 2 projects envisage synthetic accomplishments where there is not necessarily any link between the products and previous evolutionary forms, even in principle. The example given is the generation of different nucleic acid backbones, with different sugar moieties, including adaptation of polymerases such that the novel nucleic acids can be replicated. (Certainly other examples could have been used, including the generation of nucleic acids with novel base pairs). Type 3 projects have a more clear-cut ‘recapitulation of proposed evolutionary events’ trajectory as for Type 1, except that their feasibility is currently beyond our immediate abilities. (Consider that the specific example given for ‘Type 3’ here, ribocytes [described in a previous post] would be completely dependent on the prior recapitulation of a range of ribozymes, not least of which would the ribozyme polymerase example of Type 1. And although there has been considerable recent progress, even that has a way to go before a truly self-replicating ribozyme polymerase is created).

See References & Details below for some links and more information on items in this Table.


Are we to exclude ‘Type 2’ experimental projects as ‘Kon-Tiki’ projects, where there is no underlying attempt to re-create a hypothetical state or system which existed once in the past? (Such projects necessarily include those involving structures for which no evidence whatsoever exists for prior involvement in known molecular evolution). Well, that depends on one’s willingness to extend the ‘hypothetical states’ beyond the boundaries of terrestrial biosystems. One could generalize synthetic biological studies to embrace not merely life on this planet, but all potential forms of chemical life anywhere. Accordingly, studies of any artificial biosystem configuration could be seen as testing hypothetical ‘others’ not just in terms of time (the past history of Earth), but elsewhere in space. As such, this kind of research can be viewed as an adjunct of astrobiology (a topic of a previous post). But of course, such theoretical considerations need not be a primary motivation for such work, which can have the simple and pragmatic aims of advancing the understanding of nucleic acid chemistry, and the generation of possibly useful novel molecular forms.

Major Pathways and Sidelines

The Kon-Tiki expedition and its aftermath remind us that mere re-creation of a past possibility (whether historical or evolutionary) can at best be only suggestive. Skepticism towards Heyerdahl’s theories regarding the South American origins of Polynesian peoples came not from any aspect of this voyage itself, but via comprehensive additional information, principally linguistic and genetic. A proposed historical or evolutionary pathway may enter the realm of greatly enhanced plausibility if its inherent feasibility was conclusively demonstrated experimentally, but additional information is essential to shore it up as a convincing hypothesis. (If multiple lines of evidence are in agreement and no attempts to falsify the hypothesis succeed, then by consensus it may become regarded as fact, in the provisional sense that all science is a continuous fine-tuning of our understanding of the universe, where current theories may need refinement in the light of newly emerging knowledge).

It is important point to note that any hypothesis which purports to explain present arrangements through ancient underlying processes necessarily must restrict itself to broad trends for which a prima facie case can be made. The hypothesis might stipulate that an ancient state A resulted in modern state C through a definable intermediate state B, inferred from certain features of C (the known and familiar) with the postulated primordial state A. Any number of side-events peripheral to such a ‘main game’ could in principle occur without leaving discernible traces in modern times, and without corroborating evidence it is profitless to speculate on them.

By an overwhelming majority, the ‘jury’ of modern paleoanthropologists have concluded that Heyerdahl was wrong with respect to his proposed migratory path for Pacific colonization, but the ‘side issue’ of pre-Columbian contact between Polynesians and South Americans cannot be so easily dismissed. (Although as noted above, both the proposed chicken and sweet potato precedents for cross-cultural transfer remain controversial). Again, numerous voyages in historical times bridging these cultures may possibly have occurred, either in an easterly direction by Polynesians (consistent with their known ocean-going prowess, and their attainment of the remote Easter Island) or a westerly direction by South Americans (rendered feasible by the voyages of Heyerdahl and his successors). But even if so, the long-term influence of such contacts must be inferred to be minimal, and therefore should be clearly demarcated from the ‘main game’ of Pacific history.

Are there evolutionary analogs of historical side-issues? In animal biology, we can compare major body plan ‘design schemes’ of evolution with the innumerable variations on such themes which can emerge. Thus, all of the major animal body plans arose during the ‘Cambrian explosion’ of around 545 million yeas ago, and have been maintained ever since. This preservation of higher-order bodily organization of distinct major groups (termed phlya) is in marked distinction to the steady turnover of species within each phylum itself. (It has been often noted that species have finite lives just as do the individuals which comprise them). So here basic body plans are the ‘main game’, and the profusion of variations on specific body plan designs are the ‘side issues’. At an even more fundamental level of life system design are the basic operations of biological information storage and its expression, founded in all existing cellular organisms on DNA, RNA, and protein. Regardless of the possibility of alternative biological fundamental configurations, the familiar arrangements are likely to be fixed through the inherent unfeasibility of radical change within a pre-existing system.

Heyerdahl, of course, was not attempting to demonstrate the possibility of a minor historical anomaly but rather a major influence. But as we noted above, showing that something is possible in itself does not enable one to discern its genuine long-term impact. Thus, to use the ’Type 3’ example from the above Table, if ribocytes were shown to be physically feasible by advanced synthetic chemistry, then the case for their possible early existence in molecular evolution would become stronger. Yet even these ‘RNA cells’ could in principle be ‘side-issues’ rather the ‘main game’ in the development of life, if the precursor to modern DNA-RNA-protein cellular life split from even earlier developmental lineages. (In other words, peptide, proteins and DNA might have emerged during an earlier phase of the RNA World, and this lineage progressed towards modern biosystems. Other RNA-based lineages could have progressed independently towards becoming functional ribocytes, but constituted an evolutionary dead-end through competition from more efficient DNA-RNA-protein protocells).

So is that all that could be said about a successful synthetic biological ‘Kon-Tiki’ experiment? Perhaps, if it remained standing in isolation. But just as the proposed (and physically feasible) historical pathway of eastward Pacific migration from South America was discarded in the light of additional information, so too can synthetic biological insights be tested and tempered by aligning them with other biological information sources. A combination of these (perhaps involving multiple synthetic biological experiments) have the prospects for reconstructing the most probable molecular evolutionary pathways that progressed in the remote past. This higher-level data integration would necessarily involve assigning relative fitness levels to alternative molecular systems, where the bottom line for ‘fitness’ is replicative efficiency. To achieve the latter fundamental status, other systems (such as nutrient acquisition and energy generation) also have to compete for relative efficiencies. Thus, if multiple lines of synthetic biological evidence suggested a proposed specific pathway in molecular evolution had maximal fitness, its real former existence would become a solid hypothesis.

Chance vs. Necessity

But an important caveat has to be noted, which comes in at the level of deciding what in fact is a viable ‘alternative system’. If one is attempting to reconstruct ancient molecular evolutionary pathways (rather than ‘free-form’ synthetic biology paralleling Type 2 projects of the above Table), then a proposed biosystem always has to be placed in the context of its immediate precursors; or how it developed in its own right. In other words, from an assumed starting state A (for example, the early RNA World), several alternative biosystem pathways might be proposed (B, C, D…) with the necessary restriction that all must be viable precursors for later cellular stages of life. It might be possible to recreate each theoretical state B, C, and D by synthetic biology (demonstrating their physical feasibility), but to be useful for evolutionary studies, a transitional pathway leading from state A must be given as a feasible model. So while B, C and D might be physically attainable, evolutionary constraints ‘lock in’ certain alternative successors (B might be the only viable outcome). In more precise terms, going from A to C or A to D might be achievable only with intermediate forms of reduced fitness; the transition to B is favored if all intermediate forms have progressively greater fitness.

These kinds of restrictions on what are feasible evolutionary steps (even if alternative systems are physically possible) are ‘historical’ in the sense that they arise from the inherent nature of the pre-existing systems upon which future evolutionary change must build. An organized biosystem that has ‘invested’ in proceeding down one broad pathway may not be able to switch to another once the initial ‘system platform’ has been laid down. But at some earlier stage of molecular evolution, before such irreversible commitment has taken place, a point would exist where branching in either direction was feasible in principle. What determines the ‘road taken’? In an ideal analysis, among a population of competing biosystems, the complete range of different alternatives will emerge (both ‘roads’ in this analogy), where only the most reproductively competent ‘road’ (the fittest; in the face of environmental challenges) will predominate. But in practice, it may not be so simple. The initial emergence of one successful configuration may result in biosystems bearing it getting a ‘head start’ and developing even further, allowing them to out-compete potential earlier-stage alternatives showing up later. All subsequent building upon the successful system is then ‘locked in’ to its design plan. In evolutionary parlance, such scenarios have frequently been referred to as ‘frozen accidents’.

But all such early alternative systems at the outset may share certain invariant subsystems which cannot change without global loss of fitness in their normal environments. Debate over the interplay between such necessary features and chance events has been an ongoing theme in evolutionary science. ‘Chance’ in this context really refers to evolutionary ‘choices’ that are influenced by contingent factors which are difficult or impossible to predict. Such contingencies in principle could range from stochastic (purely probabilistic, flip-of-a-coin) events at the molecular level (such as the occurrence of different random mutations with very different resulting evolutionary trajectories), to external global-scale catastrophes (such as the bolide strike associated with the extinction of much of the dinosaurian lineage).

In one sense (as has been pointed out), invoking contingency in evolution says little, because selection for fitness is always contingent on environmental pressures, which inevitably will change with time. Proponents of the importance of contingency thus are usually referring to the intervention of chance-based and unpredictable strikes (metaphorically or literally) which profoundly shape evolutionary landscapes. This theme will be developed further in the succeeding post.

So what can ‘Kon-Tiki’ synthetic biological experiments, however sophisticated, have to say about evolutionary contingency? A positive result in a synthetic biological reconstruction of a postulated early biosystem demonstrates its physical possibility, in the same manner as for Kon-Tiki rafting. If more than one such systems can be devised as viable alternatives, then in principle from starting state A, these ‘options’ are B1, B2, B3….and so on. Then, the challenge is further reconstruct intermediate states between A and the alternative Bs, where each step is both evolutionary feasible (by mutation or recombination) and of demonstrable fitness value. Each of these sub-projects then is a Kon-Tiki test in its own right. Failure to find viable intermediates between A and (say) B3, but success with the others, would suggest (although not prove) that B3 was physically possible but a low-probability outcome from state A. Where is contingency in this kind of hypothetical advanced technological analysis? Well, consider two alternative evolutionary pathways (from starting point A) as B1 and B2, where the former corresponds to ‘real world’ circumstances, and the latter is an artificial construct (physically validated by synthetic biology). Now, if both of these appeared to have equally plausible evolutionary intermediates and equivalent fitness, then the actual success of B1 over its potential rival B2 could be interpreted as having occurred through the intervention of an unpredictable contingency. For example, this might operate through the extinction of an emerging population of B2 biosystems through a local environmental disaster which spared a sample of B1 competitors. The progeny of the B1 alternative could then continue to develop into a state more or less unassailable by any new emerging rivals, and take over all available habitats.

But it would be hard to make conclusive decisions in this regard, and that is why the above wording included the qualifier “appeared to have”, with respect to perceived relative fitnesses. It could continue to be argued that judging the relative fitness of alternatives B1 and B2 can only be accurately done with a full knowledge of (selective) environmental conditions in the ancient era of interest, which clearly cannot be given with complete confidence. Nevertheless, repeated tests under a range of different conditions could themselves help to resolve this, until a general consensus of scientific opinion is obtained. All of these hypothetical studies, of course, fall into the ‘Type 3’ category in the above Table, as a consequence of their ‘Kon-Tiki-like’ aspects, but which still lie in the future of the synthetic biological field. Yet the future very often reaches us much faster than we anticipate…..

Finally, a biopolyverse salute to the inspirer of this post, despite the lack of acceptance of his proposals:

Thor Heyerdahl took the Kon-Tiki

On a voyage that some thought was freaky

He took his bold notion

Across half an ocean

The idea, not raft, proved leaky

References & Details

(In order of citation, giving some key references where appropriate, but not an exhaustive coverage of the literature).

‘…..some opinion elevates it [analogy creation] into a premier position in cognitive processes….’    See an online discussion of the importance of making analogies in thought (“Analogy as the Core of Cognition”) by Douglas Hofstadter, the author of Gödel, Escher, Bach – An Eternal Golden Braid.

‘…..Thor Heyerdahl…..’    See the 2002 New York Times obituary. Heyerdahl’s best-selling account of the voyage was published in 1950. (The Kon-Tiki Expedition [various editions, including George, Allen and Unwin, London] 1950).

‘……Vital Alsar ……. expeditions….’    An account of the La Balsa expedition was published by Alsar in 1973. (La Balsa: The Longest Raft Voyage in History, by V. Alsar [with E. H. Lopez translation from Spanish]  Reader’s Digest Press, 1973). The subsequent Las Balsas expedition (involving three rafts) was even longer than the single-raft La Balsa. The Las Balsas voyage across the Pacific from South America ended in the coastal town of Ballina, New South Wales. One of these rafts is currently displayed in a local Ballina museum.

‘……a string of islands among the very many which were long ago colonized by the Polynesians….’     The term ‘long ago’ can have a very fluid definition, even on the time-scale of human existence. Although the origins of the oldest westerly Polynesian settlements can be measured in millenia, recent evidence suggest that the most remote colonizations (principally Hawaii, Easter Island [Rapa Nui] and New Zealand) occurred historically at much later times than previously thought, quite possibly as recently as 800 years ago (Hunt & Lipo 2006; Wilmshurst et al. 2011). By this reckoning,  even at the time of the Norman conquest of England, all these islands still existed in their pristine pre-human contact states, with their rich array of uniquely evolved flora and fauna.

It is ultimately Asia, rather than South America, from which the direct ancestors of Polynesians originally derive. ’   Although the general eastward direction of colonization is not in dispute, the details of when, how and from exactly where this took place have been more controversial. But in general, an interesting feature of Pacific colonization is its extreme biphasic nature: it encompasses the earliest movement of modern humans out of Africa (into Australia and New Guinea) and the most recent colonization events (into eastern Polynesia). For a recent review on this topic, see Kayser 2010. Two competing models have been the slow diffusion eastward from Melanesia as the main pathway (‘slow boat’), vs. a relatively rapid pulse of migrations stemming from Taiwan south-easterly through Melanesia and then eastward for the colonization of Polynesia (‘express train’). Most recent evidence appears to support the latter view, from both linguistic (Gray et al. 2009) and human genetic evidence (Friedlaender et al. 2008). The ‘express train’ stance is also consistent with evidence from the spread of different strain profiles of the pathogenic human stomach bacterium Helicobacter pylori (Moodley et al. 2009).

‘……evidence has been proffered suggesting that chickens found their way into domestic use by South Americans through the agency of Polynesians….’     See Storey et al., 2007 for presented evidence, and Gongora et al. 2008 for analyses contrary to the conclusions of Storey et al.  ‘……the proposal remains controversial and unproven.’    See Storey et al. 2012.

‘….the origin of the sweet potato grown for food in some Polynesian societies, but this too remains controversial …..’     It has been noted that the sweet potato could have made its way to Polynesia from South America not necessarily by human intervention, but through drifting of viable tubers on ocean currents. Recent modeling (Montenegro et al. 2007) has been offered in support of this.

‘……the possibility could not formally excluded that conditions in the past were significantly different in some crucial manner ……. for example, a change in oceanic winds or currents.’     With this point in mind, it is interest to note that is has been proposed that Polynesian voyages were enabled at a specific historical times through favorable westward winds produced through El Niño effects (Anderson et al. 2006).

‘…..experiments which have ‘Kon-Tiki’ aspects were published by Stanley Miller in 1953.‘    For Miller’s original paper, see Miller 1953. (Miller was working in the laboratory of the Nobel Prize winner Harold Urey at that time, so although he was the sole author on this paper, this classic work is often referred to as the Miller-Urey (or Urey-Miller) experiment. Miller and others continued work of this general theme with numerous refinements for many years after the initial publication.

‘…..the rafting ‘experiments’ were probably on safer ground than Miller’s work….’     While (as noted above) Heyerdahl’s beliefs regarding Pacific colonization have long been discredited, the physical ‘ancient’ design of the Kon-Tiki raft itself has not been a significant bone of contention.

‘…..the nature of the early prebiotic atmosphere…..’     There is evidence that carbon dioxide levels were very significant, and indeed without the resulting greenhouse effect, the weak sun of that ear could not have kept the mean Earth temperature above freezing (see Kasting & Ackerman 1986).

Table reference details:

‘…..generation of different nucleic acid backbones, with different sugar moieties, including adaptation of polymerases……’     Although a number of different labs have been involved in this field, in a recent study (Pinheiro et al. 2012) nucleic acid backbones with unnatural sugars have been generated, with accompanying adaptation  of polymerases which enables their faithful complementarity-based replication.

selection of novel aptamers ’   Aptamers are functional nucleic acids selected for binding specific ligands through repeated rounds of directed evolution in the laboratory. See Ellington & Szostak 1990; and Tuerk & Gold 1990 for the original papers in this area. The adaptation of polymerases to accommodate the unnatural nucleic acids of the above Pinheiro et al. (2012) study allowed the isolation of corresponding ‘unnatural’ aptamers.

‘….ribozyme polymerase……..considerable recent progress……’   See Wochner et al. 2011 . This paper and the achievement presented was also referred to in a previous post. (3 May 011).


‘….Debate over the interplay between such necessary features and chance events…..’     See the classic book Chance and Necessity (Vintage Books translation, 1971) on this theme by the French Nobel prize-winning molecular biologist Jacques Monod.

Next post: February 2013.

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