ool.weizmann.ac.il Origin Of Life Frequently Asked Questions

Answered by Doron Lancet

• 1) How did you hit upon this idea? Why lipids? Was this a "thought experiment" or did you have empirical data to work upon?
  

  The idea is actually a set of ideas. They evolved over the last 6 years. The see d was a model developed for molecular recognition, called the Receptor Affinity Distribu tion Model (RAD) (see Lancet, D., Sadovsky, E. and Seidemann, E. (1993). Probability model for molecular recognition in biological receptor repertoires: significance to the ol factory system. Proc. Natl. Acad. Sci. USA 90: 3715-3719). RAD is applicable to the unde rstanding of the interaction between receptor repertoires and and multitude s of ligands, as in the olfactory system (my last 20 years science romance) and the immune system (my Ph D topic in the 70's). Like so many scientists I was generally interested in this profound scientific/p hilosophical question of the Origin of Life, but did nothing about it. I became more seriousl y involved when beginning to attend the yearly meetings of the Israel Society for t he Orig in of Life (ILSOL) headed by Prof. Noam Lahav from the Hebrew University. Somewhere in 1994 I had this sudden insight that the RAD model was applicable to a specific appro ach to the origin of life - that of mutually catalytic networks (Stuart Kauffman from Santa fe) and h omeostatic quasi-steady states (Freeman Dyson from Princeton). I became an intellectual fan of these no-RNA no-DNA models (Dyson calls them the "Garbage Bag" models in the recent ed ition of his classical book "Origins of life (2nd Ed Cambridge U. Press). We then develop ed an entire formal, thermodynamically rigorous framework for an Origin of life scenar io that may be simulated on supercomputers (the Graded Autocatalysis Replication Domain (GARD) model. The final touch, explaining "why lipids" was through studying the papers of Luig i Luisi, which describe replicating lipid vesicles. This is elegant because lipids can sp ontaneously form supramolecular structures - micelles and vesicles. What was missing in Luisi's treatise was storable, transmittable information, which Luisi has added in in the form of RNA within the lipid vesicles. I developed the idea that lipids themselv es could store information, not through sequences but through compositions. This go t mer ged with the GARD model to provide a complete, self consistent novel scenario for the ver y early steps in the process that led to the appearance of life - "The Lipid World". The model has the best of all worlds: assemblies form spontaneously, contain compositional inf ormation, undergo evolution-like changes through forming mutually catalytic networks, and are capable of undergoing a process akin to self replication through a simple splitting proc ess that lipid assemblies are known to be capable of. Please bear in mind that very little is in the way of hand-waving, and most of it stems from rigorous and provable principles of biophysics and chemistry. We claim that we may have found the long-sought bridge between the inanimate world and a living cell.
  

• 2) What is wrong with the theory of spontaneous arising of biopolymers such as RNA or proteins?
  

  This has been elaborated on by many researchers, e.g. Robert Shapiro from NYU se e Shapiro, R. (1986). Origins: A skeptic's guide to the creation of life on Earth. N.Y., Simon & Schuster, Inc. The major obstacles: a) ANY covalent polymerization is thermodynamically unfavorable, and will occur very sluggishly if at all under pr ebiotic conditions. Non covalent assembly formation is much more likely. b) for an hone st to god RNA or DNA to form, one needs to string together very few types of very special monomers - nucleotides or similar. The prebiotic world likely was much more like a huge, pl anet scale random chemistry experiment, where millions of different types of monomers would be present. These will continuously disturb the process of forming the "purist" A,T ,G,C RNA/DNA polymers. Rather, a terribly messy polymer, often branched in crazy ways rather than linear as RNA is, and containing lots of monomers that would never be capable of the orderly, wonderful process of base-pairing and mutual complementarity c) RNA/DNA as present in today's cells are DEAD, and cannot self replicate ,except with the he lp of a complex enzymatic machinery. Thus, the idea that early on RNA was the first self-replicating entity is very tenuous. There is a chicken an egg problem that moist scientists agree on: you need long, complex RNA to code for proteins and protein s to allow such RNA to make its own copies. None could spring into existence without the ot her, and it is very difficult to see both arising simultaneously.
  

• 3) How might this "lipid life" have triggered the nucleic acid based biota we see today?
  

  This is the topic of our next papers. We foresee a slow, graded takeover, in whi ch, driven by the rudimentary capacity of lipid GARD assemblies to replicate and evolve, ch emical selection will favor a small subset of monomers, PRIOR to any polymerization. N ext, very short polymers would gradually form, inside the GARD assemblies, and driven by t he vey high local concentration of monomers (dilution is one of polymerization's problems). All this will happen within an already existing mutually catalytic network, which as can be shown mathematically, will favor some reactions and abolish others. This gradual passa ge from a very primitive network with monomers only to ones with longer and longer polymer s may in fact be the solution to the Chicken & Egg problem. But the major answer to this question - we still have to work hard to find out how this happened. But, there is consolat ion in claiming that RNA and DNA are the RESULTS of an evolutionary process rather than is prerequisites.
  

• 4) Was this in an oceanic environment? 5) Or somewhere else - say deep in the rocks?
  

  Very likely in a watery environment, but minerals from rocks may have been cruci al.
  

• 6) How could you prove this theory?
  

  Experimental proof may take football filed size "test tubes" and time scales of years (if not decades or centuries) of careful watching, entailing sophisticated nano-analysis we don't yet have today. Most likely the proof will come in the world of "in-silico" chemist ry and biology, huge supercomputer simulations. This is legitimate - after all very pro minent fields of research such as the Origin of the Universe, galaxy formation, planet accretion, super novae and black holes are studied by such means. Why not the origin of lif e - a one time event (for all we know), that may have taken millions of years, and may be utterly difficult to imitate in any size test tube, but with 2020-style computers could be looked at in utter detail and rigor.
  

• 7) How are lipid assemblies life-like? The following properties are shared by the lipid assemblies of our model and by living cells we see around us today: a) The consume chemical "foodstuff" from the environment b) They grow c) They split d) They have information content in terms of idiosyncratic chemical composition e) They display homeostasis - a capacity to preserve their properties, paticularly chemical concentrations of their constitutent components. f) They are away from equilibrium g) They depend on external energy sources h) They give rise to somewhat imperfect copies of themselves - replication or reproduction i) They may undergo selection, and therefore also evolution j) They display chaotic properties
  

• 8) Could it be anything but lipids? Any organic molecules that form assemblies could trigger the process that led to life. Life today is characterized by a very specific set of biochemicals. It should be considered a very tiny corner of the chemical space that could embody life. Prebiotical ly, it is likely that a much broader neighborhood of cjhemical space was "experimented" with. There is no reason to believe that any limitations existed, except very broad solubility and reactivity constraints.
  

• 9) Did it have to be organic? and in water? It is very likely that the answer is Yes on both counts. Carbon is required for generating the huge diversity of chemical configurations essential for our scenario, and water is essential because it is a universal solvent, that could bring together dispar atye chemicals. But it also provided the flexibility embodied in coloid-like dispersions that may exchage component readily with the environment. I short - carbon breeds diversity and water - flexibility.
  

• 10) How do you move from simple to complex? The essence of our model is that life was never simple in terms of the number of molecular species involved. Never was it a single molecule, however cunning in its properties (e.g. a single species of self-replicating RNA. We claim that life always consti tuted large assemblies, complex in terms of the number of different molecular types. Life then moved on an axis of increasing FIDELITY rahte rthan increasing complexity. Molecules within assemblies were incorporated or generated that were more and more ca pable of efficient and accurate catalysis. The catalytic network became denser and denser. This could happen, among others, by increased molecular size of the components, i.e. oligomer formation leading to polymer formation.
  

• 11) How did homochirality emerge accoring to your model? Selecting for L alanine vs D alanine is not different from selecting alanine vs beta alanine. The same selection processes that took place within assemblies could lead to the selection of one eneantiomer vs the other. Mutually catalytic networks harbor wi thin them a capacity for enentioselection.
  

• 12) Can you falsify the theory? Like any good scientific theory , our theory could be falsified. For example, because it provides (perhaps for the first time) a means to compute a time interval in which life could have emerged, and this depends on some quantitative parameters, it is pos sible to compute how long life actually took to pass from the simple assemblies stage to more elabortate form. Inconsistency with the known estimates for the time window would constitute falsification.