So, finally, these are the questions chosen to be discussed in San Sebastian next May:

1, 2, 3, 4, 6, 8(+9), 10, 12 [+14].

The organizers, after analysing the voting results (only four questions were clearly discarded), decided to include ten (instead of just eight, as initially planned) in the final list. Thus, we propose that Q09 be discussed along with Q08, and Q14 should be addressed by all contributors, in a final special session, as a way of concluding the workshop.

We are grateful to all the people who contributed to the selection process.

Find below the final list to be discussed next May, then:


List of selected questions for the Workshop OQOL’09

  • 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?

  • 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 self-organization of non living parts? – Or do you still see a kind of “vitalistic” flavour in the statements that define life as an emergent quality?

  • 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 life’s 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?

  • 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?

  • Plausibility of 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?

  • Minimal (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 protocells—the 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?

  • Minimal (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?

  • 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 life’s 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?

  • 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 Miller’s 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?


  • 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?

One response

30 01 2009
Ray Gedaly

You’ve selected a set of good questions. However, I would have liked you to additionally address the following questions:

How close are we to synthesizing life, and how can we use this to identify the “original recipe?”

Why should it be so difficult to causually produce life, i.e what conditions exist (or existed) in nature, in addition to extreme time, that would allow pre-biotic chemistry to assemble into the complexity we define as life, yet not be relatively easier for us to reproduce?

One possible answer is that we once identify the recipe, it will be easy to…

Comment by krm, blog administrator:

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