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Impressions from the San Sebastian meeting Open Questions in the Origin of Life (OQOL)
June 15, 2009 / Posted by: Yael Kovo Pier-Luigi Luisi The 2009 San Sebastian meeting on OQOL was the follow-up to an analogous meeting held in Erice, Sicily three years ago. The general idea was to identify and discuss the areas in the field that are still in the darkness, i.e. remain poorly understood despite their importance. We asked what were the reasons of our persisting ignorance, and what could we do to shed light on the dark areas. The meeting was not organized as a series of standard lectures (the usual talkand-run-away format). Instead, it was centered on several selected questions, one per half-day, which were first discussed by a panel of experts and then by all participants. The questions had been previously chosen through worldwide polling of researchers in the field. It was a very intense meeting in four days we covered eight questions. Judging from the comments of the participants, the meeting was quite successful. The intellectual level of scientific presentations and discussions was high. Although controversies surrounding the questions were not hidden and the exchange of arguments was quite intense, it all happened in a pleasant atmosphere of friendship and honesty. The intellectual level of the debates was high also because, and this was a nice characteristic of the meeting, a number of philosophical questions related to the origins of life, such as determinism, contingency, emergence, reductionism, etc. were explicitly considered. Both people who often participated in this kind of debates and those who were not used to this format enjoyed it very much. Although none of the open questions was solved, arguments surrounding each of them were clearly laid out and problems with resolving the questions were discussed. This gave everybody a deep sense of accomplishment. Extended abstracts from the presentations at the meeting will be published in the Origin of Life and Evolution of the Biosphere in a few months. Andrew Pohorille Most scientific meetings concentrate on reviewing the latest accomplishments in a given field. It is quite rare, but equally important to have a whole meeting devoted to unanswered questions and controversial issues in the field. The OQOL meeting filled this gap. I found two features of the meeting particularly appealing. One was open and in-depth discussion of both supporting and contradicting arguments related to a number of controversial issues such as RNA world vs. metabolism first scenarios or autotrophic vs. heterotrophic origins of life. Most likely each participant weighted the arguments somewhat differently, but probably everybody left with a notion that all the major issues are still far from settled. Another appealing feature was a very good combination of experimental, theoretical and, yes, epistemological arguments. This was in contrast to a view expressed by some at the last ISSOL meeting that the origin of

life is a strictly experimental field. In my opinion, this view is not just unnecessarily restrictive but makes the problem of the origin of life unsolvable. On a less bright side, I was somewhat disappointed that the group, despite its intellectual strength, did not come up with concrete approaches to solving the OQOLs that were discussed at the meeting, although I realize that my expectations might have been too high. Finally, the meeting would gain if students present in the audience were more actively involved in the discussion. In general, it was an interesting and important meeting. 1. Contingency versus determinism in the origin of life/origin of proteins. Premise. The origin of life is often seen in terms of two basic, opposite schemes, determinism and contingency. Generally, the two principles work hand in the hand, as each choice made by contingency must then comply to the natural laws and, in turn, contingency arises from a given thermodynamic asset. However, when we ask the basic question of whether the origin of life follows an obligatory deterministic pathway (absolute determinism), or whether it is due to the vagaries of contingency, the two views become again drastically opposite to each other. More precisely, according to the deterministic view (as represented most notably by Christian de Duve), the origin of life is seen as an event of very high probability: actually, it had to come out inevitably from the starting and boundary conditions (the so called gospel of inevitability). The opposite view (advocated, for example, by Jacques Monod), implies that the origin of life was due to the occurrence of several independent factors, each of them perhaps not un-deterministic, whose simultaneous and unpredictable interaction led to successive events, up to the origin of life. The question. Do you agree that the choice between these two extreme points of view cannot be done on a rational, scientific basis, and is instead for each scientist a matter of philosophical or religious belief? And, if you do not agree, which scientific arguments would you offer in favour of one or the other lines of thought? 2. Emergence and emergent properties: is life an emergent property? Premise. Although emergence is a notion with many complex sides, the general view is that emergent properties are those novel properties that arise when parts or components assemble together into a higher hierarchic order novel in the sense that they are not present in the parts or components. Most of modern scientists would consider cellular life an emergent property, as the single components are per se not living. Then The question. Do you think there are sufficient data now to say that life is indeed an emergent property, arising from the interactions and selforganization of non living parts? Or do you still see a kind of vitalistic flavour in the statements that define life as an emergent quality? 3. Heterotrophic versus autotrophic scenarios. Premise. One of the important questions relating to the origin of life problem today is the heterotrophy/autotrophy dichotomy. In an (extreme) heterotrophic scenario, the organic material supposed to have accumulated in a prebiotic world by high-energy

processes (such as those of the Miller type in a primordial atmosphere, or by impact delivery to the Earth from extraterrestrial sources) is assumed to generate the critical self-organization processes culminating in lifes origin. In sharp contrast, in an (extreme) autotrophic scenario, this kind of organic material is considered irrelevant and it is, instead, postulated that the substrates and intermediates of the chemical processes that organized themselves toward life were generated through synthetic processes within self-organized structures (e.g. from free-energy reach C-1- or C-2-organics, combined with strong inorganic reductants). The question. Do you see strong chemical arguments in favor of the one or the other scenario? And which experiments would you do/suggest, in order to possibly clarify this dichotomy? 4. On the origin of catalytic cycles Premise. In a prebiotic scenario, like that assumed by Stanley Miller in his famous experiments, once given the initial conditions, prebiotic reactions flow towards the most stable compounds, being ruled by thermodynamic control. With the free ticket of thermodynamic control, however, chemical prebiotic evolution would not have gone very far. In fact, the question of the origin of life can be abstracted as the question of the origin of enzyme-like controlled catalysis (eventually leading to genetically controlled catalysis), giving rise to sequential metabolic cycles, as opposite to chemically equilibrated reaction pathways. One line of thought considers that films of organic materials, found bound to the hot internal surfaces of inorganic tubes in contemporary hydrothermal systems, may have initiated networks of interaction between different layers that led the way towards metabolic cellular life. The question. How do you envisage the origin of sequentially catalytized reactions in a prebiotic scenario? And can you provide facts or scientific arguments, not simply beliefs, about this critical point? 5. On the origin of specific macromolecular sequences Premise. Functional proteins are copolymers with a specific, orderly sequence of bio-monomers. In the literature, some methods are described on how to make homopolymers (containing only one residue) or random polymers (mixtures of quite different casual sequences); however, there are no -or very scanty- reports on how to produce a specific co-oligopeptide or co-olinucleotide (let us say, at least, 25-30 residues-long) in many identical copies. This is also true for RNA, as in the hypothetic RNA world (see question below). The question. Do you agree that we have no good understanding about the synthesis of orderly sequences of proteins or nucleic acids, both conceptually and experimentally? Or, which approach would you suggest to tackle the problem of the synthesis of any specific sequence in many identical copies? (although we may agree that a quasi species instead of a family of exact identical copies would also do). 6. About the RNA world

Premise. The origin of life on the basis of a prebiotic family of RNAs is still a preferred scenario. This assumes, however, that RNA is formed prebiotically, while the question what made RNA? is still unanswered. In fact, until now there is not even an accepted view of a robust prebiotic synthesis of mononucleotides, despite the considerable amount of work in the field by exquisite chemists. And, even if that would be discovered, still we would need to find a prebiotic way to couple the units in a 3-5 configuration to one another. And, finally, even if this also would be known, we would have to find out how a specific macromolecular sequence could be synthesized in many identical copies (see also the question above), to give a concentration of, say, 10-12 M in solution (which implies, in turn, more than 1013 (quasi) identical copies in one liter, or ca. 107 identical copies in one microliter). One might conclude that the prebiotic synthesis of RNA is still a chimera from the scientific point of view. The question. Do you share these arguments and rather bleak view? Which experiments or arguments can you suggest to counteract these objections against the prebiotic RNA world? 7. Why thisand not that? Premise. In nature we have DNA with Thymine and RNA with Uracyl. We have DNA with desoxyribose and RNA with ribose. The question. Why dont we have in nature DNA with Uracyl and RNA with Thymine; and why not DNA with ribose and RNA with desoxyribose? 8. Proto-cellular world (a) Premise. The simplest cells on Earth contain at least 500-600 genes, and more generally a few thousand. This elicits the question, whether this high complexity is really necessary for cellular life, also in view of the fact that early cells, conceivably, could not have been so complex. Until now, however, the construction of chemical synthetic cells has not been successful, and the attempts to make DNA/Protein minimal cells with extant genes and enzymes are still based on systems with approximately a hundred genes. In other words, we are still missing the view of the early protocellsthe primitive structures from which modern cells may have arisen. The question. Do you see a way around the conundrum, that a living cell has to contain several dozens of independent specific macromolecular species and that, nevertheless, this complexity is not reasonably possible in prebiotic times? And/or: how do you envisage the structure of the simplest, early cells? 9. Proto-cellular world (b) Premise. The main building blocks of membranes in present-day prokaryotes are rather different from one another: in bacteria (like in eukaryotes) phospholipids are made of fatty acids, linked to the glycerol group (G3P) by ester bonds, whereas the phospholipids of archeabacteria are isoprenoid derivatives linked to glycerol (the

stereoisomer, G1P) through ether bonds. And consider the extremely important role of hopanoids and steroids in modern bacterial and eukaryotic membranes. The question. Do you think that these radical molecular differences show that the issue of compartments was not relevant until late stages in the origin of life? Or do you consider that compartmentalization was still an early landmark, phospholipid diversity being easily explained as a later evolutionary adaptation to extreme environments, for instance? 10. Life as unity or confederacy Premise. Many sciences have conventionally (if implicitly) referred to life as a unitary concept, and all too often, we speak of the origin of life as if it were essentially one kind of unified event: a transition from no life to life on Earth. An alternative premise would be that life is a collection of coupled but still distinguishable subsystems, each with its own recognizable dynamics and requirements for stability. In that case the origin of life could involve a sequence of transitions understandable in somewhat independent terms. For instance, one could take separately the appearance of self-reproducing systems and the formation of vesicles, biogenesis of proteins different from setting up metabolic cycles, origin of reductive power different from prebiotic chemistry, etc The degree of both contingency and of what some have called irreducible complexity in life will depend strongly on how tightly or loosely its subsystems are coupled. The question. Do you agree with this possible alternative view of life origin? And if yes, what is the proper way to apply the notions of interdependency versus subsystem independence, in the understanding of both the modern function of life and of its origin? Can a different understanding of the organization and stability of life today lead to better sequences of investigations of lifes origins? If life is not a totally unitary notion, but rather a confederacy of coupled processes, can the recognition of this decomposition help us define the nature and process of origins of life in ways that do not lead to contradiction and confusion? 11. Ecology and individuality Premise. An ecosystem think of primitive bacteria in our context can be understood as a collection of interactions and dependencies which arise from the nature of the individuals that participate in it. Alternatively, an ecosystem could be understood as a cooperative entity, whose structure and dynamics obey principles of their own, which may even determine the kinds of individuality in the sense assumed by Mendelian inheritance and Darwinian competition and selection which can arise within it. Certainly ecosystems and the individuals within them co-evolve (though in two very different senses of the term evolve); but whether one believes that ecology comes from individuality, or the converse, may determine where one looks for simplifying regularities or predictable features, and the direction in which one infers causation. The question. How should we best think about the organizational principles that govern bacterial ecology and individuality, and the

directions in which causation or constraint flow between these levels? In what respects might individuality be a subordinate concept to ecology, and in what senses is ecological order the subordinate concept? 12. Defining the very origin of life Premise. Defining life in an universal way is notoriously a difficult or impossible task, but also the notion of origin of life appears to be rather confuse. Some authors talk about origin of life at the level of the origin of low molecular weight compounds, obtainable either through hypothermal vents; or the pyrite reaction; or by Millers type of processes. However, you can have all low molecular weight compounds of this world, and you will never be able to make life, as life only arises at the level of specific macromolecular sequences like enzymes, DNA, RNA. The question. Do you agree that we should have a critical review of the terminology of origin of life, and, for example, not use this term at the level of low mol. weight compounds (where we have prebiotic chemistry, or origin of reductive power), and restrict it instead to the level of the biogenesis of specific macromolecules and their interactions? 13. About the anthropic principle (AP) Premise. There is no doubt that life on Earth is made possible by particular cosmic conditions (distance from the sun, the moon, force of gravity, speed of light, etc) and of the particular cosmic constants, as minimal changes in one of those constants would make life on Earth impossible. Although there are several versions of the AP, the main predicament in the original strong version of AP is that this fine tuning is not accidental, but exists in order to make life and mankind and human consciousness possible. Life, then, is some sort of cosmic imperative. Several people object to this view, saying either that it is a tautology, or that it corresponds to a form of intelligent design claim (although this is not expressly mentioned by the authors of the anthropic principle). The question. Do you accept the anthropic principle as a scientific view? Something that should be taken seriously by people working in the origin of life? Or would you consider it as a particular case of intelligent design theories? 14. On the entire field of the origin of life Premise. The picture given until now suggests that we have not yet clarified the prebiotic synthesis of RNA, nor the biogenesis of macromolecular sequences, nor the development of the genetic code, nor the structure of the early cells. And probably several other points of ignorance could be added. The question. would you agree with the statement, that from the conceptual point of view the field has not progressed much since the early experiments of Stanley Miller? And why do you think/not think so?

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13 02 2009

TESSERA (12:40:55) : Q01: Contingency versus determinism in the origin of life/origin of proteins The main difference between determinism and contingency is the part of chance which is important in contingency. The apparition of Life is very likely related to very unlikely conditions. Thus chance should have plaid a major role. Q02: Emergence and emergent properties: is life an emergent property? The concept of emergence should be defined rigorously. If a strong definition is considered, i.e. apparition of new properties which cannot be explained by the properties of the components, then emergence appears as a magic concept. I think, of course, that the apparition of life is not emergent with this strong definition. I think that it can be explained by the physical properties of its componnets. Q15 (David Deamers very good question): Would you agree that evolution began when life began? I agree with that sentence except that I would reverse the terms: do you agree that life began when evolution began? Actually my thesis is that life began when evolution began. But, in addition, it is necessary to define the conditions of what can be an evolution of a particular system: - the system should be in a state far from its thermodynamic equilibrium and remain such during its evolution, - the system should be able to auto-replication, - the apparition of variants should be possible and these variants should be able to auto-replication too. Reply