This is the Bibliography "C" page for authors' surnames beginning 
[Left: Organic chemist and origin-of-life theorist, Graham Cairns-Smith's, "Seven Clues to the Origin of Life" (1985). Though a devout materialist, Cairns-Smith demolishes all other origin-of-life theories except his own clay theory, which however, as Wikipedia notes, "the 'clay theory' of abiogenesis has not been widely accepted"! See `tagline' quotes below (my emphasis bold), all from Cairns-Smith's books.]
with "C", of books and journals which I may refer to in my book outline, "Problems of Evolution."
© Stephen E. Jones, BSc. (Biology)
BIBLIOGRAPHY "C"
Cairns-Smith, A.G., 1971, "The Life Puzzle: On Crystals and Organisms and on the Possibility of a Crystal as an Ancestor," University of Toronto Press: Toronto ON, Canada.
Cairns-Smith, A.G., 1982, "Genetic Takeover and the Mineral Origins of Life," Cambridge University Press: Cambridge UK, Reprinted, 1987.
Cairns-Smith, A.G., 1985, "Seven Clues to the Origin of Life: A Scientific Detective Story," Cambridge University Press: Cambridge UK, Reprinted, 1993.
Calder, N., 1984, "Timescale: An Atlas of the Fourth Dimension," Chatto & Windus: London.
Calvin, M., 1969, "Chemical Evolution : Molecular Evolution Towards the Origin of Living Systems on the Earth and Elsewhere," Clarendon Press: Oxford UK.
Calvin, M. & Jorgenson, M.J., 1968, "Bio-Organic Chemistry: Readings from Scientific American," W.H. Freeman & Co: San Francisco CA.
Calvin, W.H., 1986, "The River That Flows Uphill: A Journey from the Big Bang to the Big Brain," Macmillan: New York NY.
Calvin, W.H., 1991, "The Ascent of Mind: Ice Age Climates and the Evolution of Intelligence," Bantam Books: New York NY.
Calvin, W.H., 1997, "How Brains Think: Evolving Intelligence, Then and Now," Phoenix: London, Reprinted, 1998.
Camp, A.L., 1994, "The Myth of Natural Origins: How Science Points to Divine Creation," Ktisis Publishing: Tempe, AZ.
Campbell, B.G. & Loy, J.D., 1995, "Humankind Emerging," Harper Collins: New York NY, Seventh edition.
Campbell, J., 1982, "Grammatical Man: Information, Entropy, Language and Life," Penguin: Harmondsworth UK, Reprinted, 1984.
Campbell, J., 1989, "The Improbable Machine: What the New Discoveries in Artificial Intelligence Reveal about How The Mind Really Works," Touchstone Books: New York NY, Reprinted, 1990.
Campbell, J.H. & Schopf, J.W., eds, 1994, "Creative Evolution?!: Proceedings of a Symposium Sponsored by the Center for the Study of Evolution and the Origin of Life at the University of California, Los Angeles, in March, 1993," Jones & Bartlett: London.
Campbell, N.A., Reece, J.B. & Mitchell, L.G., 1999, "Biology," [1987], Benjamin/Cummings: Menlo Park CA, Fifth edition.
Campolo, A., 1983, "A Reasonable Faith: The Case for Christianity in a Secular World," Word Publishing: Dallas TX .
Carey, J., ed., 1995, "The Faber Book of Science," Faber & Faber: London.
Carlson, R.F., ed., 2000, "Science & Christianity: Four Views," Intervarsity Press: Downers Grove IL.
Carnell, E.J., 1952, "An Introduction to Christian Apologetics," [1948], Eerdmans: Grand Rapids MI, Fourth edition.
Carr, A., 1963, "The Reptiles," Time/Life Books: Netherlands, Reprinted, 1964.
Carrington, R., 1956, "A Guide to Earth History," Penguin: Harmondsworth UK, Reprinted, 1958.
Carrington, R., 1963a "The Mammals," Time/Life Books: Netherlands, Reprinted, 1965.
Carrington, R., 1963b "A Million Years of Man: The Story of Human Development as a Part of Nature," Mentor, New York NY, Reprinted, 1964.
Carroll, J., 1993, "Humanism: The Wreck of Western Culture," Fontana: London.
Carroll, R.L., 1988, "Vertebrate Paleontology and Evolution," W.H. Freeman & Co: New York NY.
Carroll, R.L., 1997, "Patterns and Processes of Vertebrate Evolution," Cambridge University Press: Cambridge UK.
Carroll, S.B., 2005, "Endless Forms Most Beautiful: The New Science of Evo Devo," W.W. Norton & Co: New York NY.
Carroll, V. & Shiflett, D., 2002, "Christianity on Trial: Arguments Against Anti-Religious Bigotry," Encounter Books: San Francisco CA.
Carter, R., 2002, "Consciousness," Weidenfeld & Nicolson: London.
Casti, J.L., 1989, "Paradigms Lost: Images of Man in the Mirror of Science," Cardinal: London.
Casti, J.L., 2000, "Paradigms Regained: A Further Exploration of the Mysteries of Modern Science," Abacus: London, Reprinted, 2001.
Caudill, E., 1997, "Darwinian Myths: The Legends and Misuses of a Theory," The University of Tennessee Press: Knoxville TN.
Cavalli-Sforza, L.L. & Bodmer, W.F., 1971, "The Genetics of Human Populations," Dover: Mineola NY, Reprinted, 1999.
Cazeau, C.J., 1986, "Science Trivia: From Anteaters to Zeppelins," Plenum Press: New York NY.
Chalmers, A.F., 1976, "What is this thing called Science?: An Assessment of the Nature and Status of Science and its Method," University of Queensland Press: St Lucia Qld, Australia, Second edition, Reprinted, 1994.
Chalmers, A.F., 1990, "Science and its Fabrication," Open University Press: Milton Keynes UK.
Chambers, P., 1999, "Life on Mars: The Complete Story," Blandford: London.
Chancellor, J., 1973, "Charles Darwin," Taplinger: New York NY, Reprinted, 1976.
Chapman, C., 1972, "Christianity on Trial," Lion: Tring UK, Reprinted, 1981.
Cherfas, J., ed., 1983, "Darwin Up to Date: A New Scientist Guide," IPC Magazines: London.
Chesterton, G.K., 1908, "Orthodoxy: A Personal Philosophy," Fontana: London, Reprinted, 1961.
Chiari, J., 1973, "The Necessity of Being," Gordian Press: New York NY.
Chittick, D.E., 1984, "The Controversy Roots of the Creation-Evolution Conflict," Multnomah Press: Portland OR, Reprinted, 1993.
Chomsky, N., 1988, "Language and Problems of Knowledge: The Managua Lectures," MIT Press: Cambridge MA, Tenth printing, 1999.
Chown, M., 1993, "Afterglow of Creation: From the Fireball to the Discovery of Cosmic Ripples," Arrow: London.
Churton, T., 1987, "The Gnostics," Weidenfeld & Nicholson: London.
Cicero, 1972, "The Nature of the Gods," McGregor, H.C.P., transl., Penguin: Harmondsworth UK, Reprinted, 1986.
Ciochon, R.L., Olsen, J. & James, J., 1991, "Other Origins: The Search for the Giant Ape in Human Prehistory," Gollancz: London.
Clack, J.A., 2002, "Gaining Ground: The Origin and Evolution of Tetrapods," Indiana University Press: Bloomington IN.
Clark, G.H., 1952, "A Christian View of Men and Things," The Trinity Foundation: Jefferson MD, Second edition, 1991.
Clark, G.H., 1993, "An Introduction to Christian Philosophy," [1968], The Trinity Foundation: Jefferson MD, Second edition.
Clark, K.J., ed., 1993, "Philosophers Who Believe: The Spiritual Journeys of Eleven Leading Thinkers," Intervarsity Press: Downers Grove IL.
Clark, R.E.D., 1946, "Creation," Tyndale Press: London, Reprinted, 1953.
Clark, R.E.D., 1948, "Darwin: Before and After: The History of Evolutionary Theory," Paternoster: London, Reprinted, 1972.
Clark, R.E.D., 1949, "The Universe: Plan or Accident?: The Religious Implications of Modern Science," Paternoster: London, Third edition, 1961.
Clark, R.E.D., 1967, "The Christian Stake in Science," Paternoster: Exeter UK.
Clark, R.T. & Bales, J., 1966, "Why Scientists Accept Evolution," Baker: Grand Rapids MI, Second printing, 1967.
Clark, R.W., 1985a, "The Life of Ernst Chain: Penicillin and Beyond," Weidenfeld & Nicolson: London.
Clark, R.W., 1985b, "The Survival of Charles Darwin: A Biography of a Man and an Idea," Random House: New York NY.
Clark, R.L., 1998, "God, Religion and Reality," SPCK: London.
Clark, W.E.L.G., 1962, "The Antecedents of Man: An Introduction to the Evolution of the Primates," [1959], Quadrangle: New York, Revised, Reprinted, 1978.
Cloud, P., 1978, "Cosmos, Earth, and Man: A Short History of the Universe," Yale University Press: New Haven CT.
Coder, S.M. & Howe, G.F., 1966, "The Bible, Science and Creation," [1965], Moody Press: Chicago IL, Revised.
Cloud, P., 1988, "Oasis in Space: Earth History from the Beginning," W.W. Norton: New York NY.
Coffin, H.G. & Brown, R.H., 1983, "Origin by Design," Review and Herald Publishing Association: Washington DC.
Cohen, J. & Massey, B., 1982, "Living Embryos," [1963], Pergamon Press: Oxford UK, Third edition.
Cohen, J. & Stewart, I., 1994, "The Collapse of Chaos: Discovering Simplicity in a Complex World," Penguin: London, Reprinted, 1995.
Cohen, J. & Stewart, I., 2002, "What Does a Martian Look Like?: The Science of Extraterrestrial Life," Ebury Press: London, Reprinted, 2004.
Cohn-Sherbok, D. & Lewis, C., eds, 1995, "Beyond Death: Theological and Philosophical Reflections on Life After Death," Macmillan: Basingstoke UK.
Colbert, E.H., 1997, "The Age of Reptiles," [1965], Dover: Mineola NY, Revised.
Colbert, E.H., 1989, "Digging Into the Past: An Autobiography," Dembner: New York NY.
Colbert, E.H. & Morales, M., 1990, "Evolution of the Vertebrates: A History of the Backboned Animals Through Time," [1955], John Wiley & Sons: New York NY, Fourth edition, Second printing, 1992.
Collins, F.S., 2007, "The Language of God: A Scientist Presents Evidence for Belief," Free Press: New York NY.
Collins, H.M. & Pinch, T., 1993, "The Golem: What Everyone Should Know About Science," Cambridge University Press: Cambridge UK, Reprinted, 1996.
Collinson, D., 1987, "Fifty Major Philosophers: A Reference Guide," Routledge: London.
Colp, R., 1977, "To Be an Invalid: The Illness of Charles Darwin," University of Chicago Press: Chicago IL.
Colson, C.W. & Morse, A., 1997, "Burden of Truth: Defending Truth in an Age of Unbelief," Tyndale: Wheaton IL.
Colson, C.W. & Pearcey, N.R., 1999, "How Now Shall We Live?," Tyndale: Wheaton IL.
Comins, N.F., 1993, "What If the Moon Didn't Exist?: Voyages to Earths That Might Have Been," HarperCollins: New York NY.
Conklin, E.G., 1943, "Man Real and Ideal: Observations and Reflections on Man's Nature, Development, and Destiny," Charles Scribner's Sons: New York NY.
Conway Morris, S., 1998,"The Crucible of Creation: The Burgess Shale and the Rise of Animals," Oxford University Press: Oxford UK, Reprinted, 1999.
Conway Morris, S., 2000, "Evolution: Bringing Molecules into the Fold," Cell, Vol. 100, January 7.
Conway Morris, S., 2003, "Life's Solution: Inevitable Humans in a Lonely Universe," Cambridge University Press: New York NY.
Cook, P., 2006, "Evolution versus Intelligent Design: Why all the Fuss?: The arguments for both sides," New Holland Publishers: Sydney NSW, Australia.
Cookson, W., 1994, "The Gene Hunters: Adventures in the Genome Jungle," Aurum Press: London.
Copan, P., 1998, "True for You, but Not for Me: Deflating the Slogans That Leave Christians Speechless," Bethany House Publishers: Minneapolis MN.
Copi, I.M., 1986, "Introduction to Logic," [1953], Macmillan Publishing Co: New York, Seventh edition.
Coppedge, J.F., 1973, "Evolution: Possible or Impossible?," Zondervan, Grand Rapids MI, Seventh printing, 1980.
Corey, M.A., 1993, "God and the New Cosmology: The Anthropic Design Argument," Rowman & Littlefield: Lanham MD.
Corey, M.A., 1994, "Back to Darwin: The Scientific Case for Deistic Evolution," University Press of America: Lanham MD.
Corey, M.A., 1995, "The Natural History of Creation: Biblical Evolutionism and the Return of Natural Theology," University of America Press: Lanham MD.
Corey, M.A., 2001, "The God Hypothesis: Discovering Design in Our `Just Right' Goldilocks Universe," Rowman & Littlefield: Lanham MD.
Cornell, J., ed., 1989, "Bubbles, Voids and Bumps in Time: The New Cosmology," Cambridge University Press: Cambridge UK, Reprinted, 1991.
Corner, M., 1991, "Does God exist? Bristol Classical Press: Bristol UK.
Corrick, J.A., 1987, "Recent Revolutions in Biology," Franklin Watts: New York NY.
Coulson, C.A., 1955, "Science and Christian Belief," Fontana: London, Reprinted, 1958.
Coveney, P. & Highfield, R., "The Arrow of time: A Voyage Through Science to Solve Time's Greatest Mystery," W.H. Allen: London, 1990.
Cox, C.B. & Moore, P.D., 1993, "Biogeography: An Ecological and Evolutionary Approach," [1973], Blackwell Science: London, Fifth edition, Reprinted, 1995.
Craig, W.L., 1994, "Reasonable Faith: Christian Truth and Apologetics," [1984],Crossway Books: Wheaton IL, Revised edition.
Crawford, M. & Marsh, D., 1989, "The Driving Force: Food, Evolution and the Future," Heinemann: London.
Cremo, M.A. & Thompson, R.L., 1994, "The Hidden History of the Human Race: Major Scientific Coverup Exposed," Govardhan Hill: Badger CA.
Crick, F.H.C., 1966, "Of molecules and Men," University of Washington Press: Seattle WA.
Crick, F.H.C., 1981, "Life Itself: Its Origin and Nature," Simon & Schuster: New York NY.
Crick, F.H.C., 1988, "What Mad Pursuit: A Personal View of Scientific Discovery," Penguin: London, Reprinted, 1990.
Crick, F.H.C., 1994, "The Astonishing Hypothesis: The Scientific Search for the Soul," Touchstone: New York NY, Reprinted, 1995.
Croft, L.R., 1988, "How Life Began," Evangelical Press: Durham UK.
Cromer, A., 1993, "Uncommon Sense: The Heretical Nature of Science," Oxford University Press: New York NY.
Croswell, K., 1995, "The Alchemy of the Heavens: Searching for Meaning in the Milky Way," Anchor: New York NY.
Cronin, H., 1991, "The Ant and the Peacock: Altruism and Sexual Selection From Darwin to Today," Cambridge University Press: Cambridge UK, Reprinted, 1993.
Croswell, K., 1997, "Planet Quest: The Epic Discovery of Alien Solar Systems, "Free Press: New York NY.
Crystal, D., 1997, "The Cambridge Encyclopedia of Language," [1987], Cambridge University Press: Cambridge UK, Second edition, Second printing, 2000.
Currey, J.D., 2002, "Bones: Structure and Mechanics," Princeton University Press: Princeton NJ.
Cutler, A., 2003, "The Seashell on the Mountaintop: A Story of Science, Sainthood and the Humble Genius Who Discovered a New History of the Earth," Heinemann: London, Reprinted, 2004.
Cziko, G., 1995, "Without Miracles: Universal Selection Theory and the Second Darwinian Revolution," MIT Press: Cambridge MA.
Stephen E. Jones, BSc. (Biology).
My other blog: TheShroudofTurin
"There is no difficulty in principle in accounting for the existence of many different kinds of proteins. A chain of 150 amino acid units represents quite a small protein; but with 20 alternative possibilities for each link the total number of different chain sequences that are possible is 20150, i.e. 10195-far more than `the number of electrons in the universe'-and most proteins are far longer than 150 units. But the central problem remains: how can diversity of sequence give rise to such a rich diversity of function? Why is it, for example, that the sequence ... corresponds to a molecule that can store oxygen, while ... , although quite incompetent as a one-molecule oxygen cylinder, is very good at breaking up RNA molecules by splitting just one kind of bond in the main chain in just one way? Then again, how is it that ... lacks any appetite for RNA but has a neat way of destroying bacteria by unstitching their overcoats? How can specific complex functions be carried out by such molecular cryptograms? The broad answer seems to be this: the 'cryptogram'- the primary structure-determines in detail the way in which the chain will collapse on itself, its tertiary structure. The `cryptogram' may thus determine accurately the form of a piece of machinery about a millionth of a centimetre across." (Cairns-Smith, A.G., "The Life Puzzle: On Crystals and Organisms and on the Possibility of a Crystal as an Ancestor," University of Toronto Press: Toronto ON, Canada, 1971, pp.34-35).
"Now, how would you go about making a machine which could reproduce itself? ... The mathematician, von Neumann, demonstrated in the 1940s that a self-reproducing machine was in principle quite possible-and he outlined a general design (Taub, 1963; Moore, 1964). Von Neumann imagined some kind of stockroom containing fairly simple mechanical parts-such as screws, metal plates, wire, and so on. The problem was to invent a machine that could move about such a stockroom selecting the pieces required to make another machine like itself, and then proceed to do so. The centre of von Neumann's design was a set of instructions written, say, on magnetic tape or punched cards, giving an account of how to make the rest of the machine-where to find the parts and how to put them together. The machine would include a manufacturing unit which could follow the instructions and act on them. There is a special point about the instructions themselves, however; they could not be remade by following instructions that were different from themselves. ... At some point it must be the cards themselves that instruct their own formation, i.e. the cards must be replicated. Only in this way can an infinite regression be avoided. So in addition to a manufacturing unit that can make all kinds of things by following instructions, there must be another unit with the more limited task of copying them. ... Von Neumann's machine solves the problem of 'self-reproduction' in much the same way as it is solved in organisms: by separating the system formally into two parts. One part is completely coded in the form of replicable plans for its construction held in the other part. The machine has a phenotype and a genetic material (which may be cardboard) holding a genotype." (Cairns-Smith, 1971, pp.52-53).
"But these processes do not occur in vacuo. DNA, RNA, and protein are made out of units which must either be provided by the environment or synthesised by the cell from molecules which are provided. In the latter case whole teams of enzymes may be required. But even if the units are already available in the general environment, the replication of DNA still needs at least one protein, the synthesis of RNA another, and the synthesis of protein needs yet another polymerising enzyme, together with at least a couple of dozen more proteins in the enzymes which prime the transfer RNAs. To make one protein the cell already has to have dozens of proteins. There is nothing immediately illogical in this situation: a factory for making nuts and bolts can be made with the help of nuts and bolts, but it does mean that a cell must inherit more than a book of instructions from its parent. It must inherit also enough pre-formed equipment to read the book. It must inherit a `minimum phenotype'. A reproducing cell, then, must consist of at least a minimum phenotype together with the instructions required to reproduce it-a minimum genotype. Morowitz (1966) has estimated that for a minimum cell consistent with the current viewpoint of molecular biology one would need at least 45 proteins. ... It is still a gross oversimplification since, among other things, it ignores reactions required to provide energy for the various processes, as well as essential mechanical structures such as cell membranes. The problem of the origin of life is simply that any conceivable such minimum unit would seem to be necessarily far too complex to have arisen by chance-to have `nucleated' spontaneously-under any reasonable circumstances. `Life can only come from life' is no longer a dogma as it was in the immediate post-Pasteur era: but it nevertheless seems that life in fact always does arise this way, and that in nature it must-for any form built on the modern DNA -> protein design." (Cairns-Smith, 1971, pp.60-61).
"Surely there was a radically simpler plan to begin with. What was it like? Von Neumann's 'self-reproducing' machines seem to indicate that quite a complex phenotype, together with a corresponding genotype is essential for any reproducing system. Is there a way out? There must be if life really did originate spontaneously as a reasonably probable physico-chemical event during the history of the Earth." (Cairns-Smith, 1971, pp.61-62. Emphasis original).
"It seems to me that the idea of coupling agents putting together polypeptides on a lifeless Earth adds another dimension of unreality to an already unreal line of thought. Remember that primordial simulations generally give only low yields of amino acids. Remember that the products are tars and that suggestions for prevital work-up procedures are usually absent. Remember the difficulties anyway in building up concentrations of solutions of amino acids or of the cyanide or phosphate to make a coupling agent. Remember that even from laboratory bottles the agents in question do not work very well. Remembering all that, now add the thought that coupling agents are rather unspecific. If a well chosen coupling agent under well chosen laboratory conditions can effectively join the acyl group A to the nucleophile B that is because among the choices exercised by the experimenter was the crucial one of only putting A and B into a flask for the coupling agent to couple. Compared with such carefully arranged marriages the affairs of a primordial soup would have been grossly promiscuous." (Cairns-Smith, A.G., 1982, "Genetic Takeover and the Mineral Origins of Life," Cambridge University Press: Cambridge UK, Reprinted, 1987, pp.52-53).
"One can get an impression of what is needed in practice for the synthesis of peptides by considering the machinery that is used in automated procedures. One such piece of equipment is shown in figure 1.11. Merrifield, Stewart & Jernberg (1966) describe its construction and operation in nine close pages of diagrams and descriptions. I quote (more or less at random) from the middle of their paper: `... the rear disk contains a center port and one circumferential port which are joined by a 1.5 mm hole within the disk. As this disk is turned it connects one at a time the 12 inlet ports to the central outlet port. A leak-free seal between the two teflon disks of the valve ...' And that is one of the less terse passages. Not shown in figure 1.11 is a programmer, like a musical box drum, that puts appropriate operations (mixings, rinsings, shakings, etc.) in sequence. There have to be many pegs on the drum because one cycle of the automatic synthetic procedure that extends the peptide chain by one unit requires nearly 90 steps. Now I am not saying that for peptide synthesis without human intervention there has to be something physically like Merrifield's machine. There does not have to be that particular piece of engineering. But I think there has to be engineering. Another example of automatic peptide synthesis is the synthesis by the ribosome in the modern cell. ... There are no tubes or valves or metering pumps here: but in the design of the ribosome, the adaptor RNA molecules and their activating enzymes; in the whole system, with its message tapes and its code, there is surely at least as much engineering as in Merrifield's machine. ... Perhaps there is some other way of making peptides with more or less specified amino acid sequences; and perhaps this way does not need detailed control. Perhaps it could then have operated before there was life on Earth, before that engineer, natural selection, appeared on the scene. But it is difficult to see how this could have been so. I think we would know by now if there was some much easier way." (Cairns-Smith, 1982, pp.53,55).
"The implausibility of prevital nucleic acid If it is hard to imagine polypeptides or polysaccharides in primordial waters it is harder still to imagine polynucleotides. But so powerful has been the effect of Miller's experiment on the scientific imagination that to read some of the literature on the origin of life (including many elementary texts) you might think that it had been well demonstrated that nucleotides were probable constituents of a primordial soup and hence that prevital nucleic acid replication was a plausible speculation based on the results of experiments. There have indeed been many interesting and detailed experiments in this area. But the importance of this work lies, to my mind, not in demonstrating how nucleotides could have formed on the primitive Earth, but in precisely the opposite: these experiments allow us to see, in much greater detail than would otherwise have been possible, just why prevital nucleic acids are highly implausible. Let us consider some of the difficulties. First, as we have seen, it is not even clear that the primitive Earth would have generated and maintained organic molecules. All that we can say is that there might have been prevital organic chemistry going on, at least in special locations. Second, high-energy precursors of purines and pyrimidines had to be produced in a sufficiently concentrated form (for example at least 0.01 M HCN). Third, the conditions must now have been right for reactions to give perceptible yields of at least two bases that could pair with each other. Fourth, these bases must then have been separated from the confusing jumble of similar molecules that would also have been made, and the solutions must have been sufficiently concentrated. Fifth, in some other location a formaldehyde concentration of above 0.01 M must have built up. Sixth, this accumulated formaldehyde had to oligomerise to sugars. Seventh, somehow the sugars must have been separated and resolved, so as to give a moderately good concentration of, for example, D-ribose. Eighth, bases and sugars must now have come together. Ninth, they must have been induced to react to make nucleosides. (There are no known ways of bringing about this thermodynamically uphill reaction in aqueous solution: purine nucleosides have been made by dry-phase synthesis, but not even this method has been successful for condensing pyrimidine bases and ribose to give nucleosides (Orgel & Lohrmann, 1974).) Tenth, whatever the mode of joining base and sugar it had to be between the correct nitrogen atom of the base and the correct carbon atom of the sugar. This junction will fix the pentose sugar as either the α- or ß-anomer of either the furanose or pyranose forms ... For nucleic acids it has to be the ß-furanose. (In the dry-phase purine nucleoside syntheses referred to above, all four of these isomers were present with never more than 8 % of the correct structure.) Eleventh, phosphate must have been, or must now come to have been, present at reasonable concentrations. (The concentrations in the oceans would have been very low, so we must think about special situations - evaporating lagoons and such things (Ponnamperuma, 1978).) Twelfth, the phosphate must be activated in some way - for example as a linear or cyclic polyphosphate - so that (energetically uphill) phosphorylation of the nucleoside is possible. Thirteenth, to make standard nucleotides only the 5'-hydroxyl of the ribose should be phosphorylated. (In solid-state reactions with urea and inorganic phosphates as a phosphorylating agent, this was the dominant species to begin with (Lohrmann & Orgel, 1971). Longer heating gave the nucleoside cyclic 2',3'-phosphate as the major product although various dinucleotide derivatives and nucleoside polyphosphates are also formed (Osterberg, Orgel & Lohrmann, 1973).) Fourteenth, if not already activated - for example as the cyclic 2',3'- phosphate - the nucleotides must now be activated (for example with polyphosphate; Lohrmann, 1976) and a reasonably pure solution of these species created of reasonable concentration. Alternatively, a suitable coupling agent must now have been fed into the system. Fifteenth, the activated nucleotides (or the nucleotides with coupling agent) must now have polymerised. Initially this must have happened without a pre-existing polynucleotide template (this has proved very difficult to simulate (Orgel & Lohrmann, 1974)); but more important, it must have come to take place on pre-existing polynucleotides if the key function of transmitting information to daughter molecules was to be achieved by abiotic means. This has proved difficult too. ...Sixteenth, the physical and chemical environment must at all times have been suitable - for example the pH, the temperature, the M2+ concentrations. Seventeenth, all reactions must have taken place well out of the ultraviolet sunlight; that is, not only away from its direct, highly destructive effects on nucleic acid-like molecules, but away too from the radicals produced by the sunlight, and from the various longer lived reactive species produced by these radicals. Eighteenth, unlike polypeptides, where you can easily imagine functions for imprecisely made products (for capsules, ion-exchange materials, etc.), a genetic material must work rather well to be any use at all - otherwise it will quickly let slip any information that it has managed to accumulate. Nineteenth, what is required here is not some wild one-off freak of an event: it is not true to say `it only had to happen once'. A whole set-up had to be maintained for perhaps millions of years: a reliable means of production of activated nucleotides at the least. Now you may say that there are alternative ways of building up nucleotides, and perhaps there was some geochemical way on the early Earth. But what we know of the experimental difficulties in nucleotide synthesis speaks strongly against any such supposition. However it is to be put together, a nucleotide is too complex and metastable a molecule for there to be any reason to expect an easy synthesis. You might want to argue about the nineteen problems that I chose: and I agree that there is a certain arbitrariness in the sequence of operations chosen. But if in the compounding of improbabilities nineteen is wrong as a number that would be mainly because it is much too small a number. If you were to consider in more detail a process such as the purification of an intermediate you would find many subsidiary operations - washings, pH changes and so on. (Remember Merrifield's machine: for one overall reaction, making one peptide bond, there were about 90 distinct operations required.)." (Cairns-Smith, 1982, p.56-59. Emphasis original).
"Problems for primitive heterotrophs Let us suppose that all the difficulties that we have been discussing were somehow overcome, and let us now consider how the very first organisms might have fared. According to the doctrine of chemical evolution these organisms were heterotrophs, that is to say they depended on organic foods. The diet of primordial soup was so adequate, it is said, that these organisms had no need for metabolic pathways to begin with. Such pathways could evolve gradually as the foods ran out (by the mechanism proposed by Horowitz in 1945; see figure 1.12). A -> B -> C -> D .... According to Horowitz (1945 [Horowitz, N.H., "On the Evolution of Biochemical Syntheses," Proc. Natl Acad. Sci. USA, Vol. 31, No. 6, June 1945, pp.153-157]), a metabolic pathway would have evolved backwards. D was at first a vital molecule available in the environment. D gradually ran out, giving organisms time to evolve an internal source - by converting C, some simpler precursor, that was still in the environment. As C ran out there would then be selection pressures to find some other environmental molecule, B, and the means to convert it to C. Hence complex molecules that were originally provided by a primordial soup came to be made instead from simple commonly available molecules such as CO2 and N2. To have one's food provided sounds like an easy sort of life, but in reality there would be great difficulties with such an idea. There are problems of assimilation. To be a heterotroph implies an ability to recognise molecules, or at the very least to distinguish between classes of them. For the eventual evolution of metabolic pathways, specific recognition devices would be required. Thinking along the lines of current means of biomolecular control, some kind of structure would seem to be needed that could form specific sockets corresponding to the molecules in the environment. But until you have the ability to recognise at least some molecular units, how do you reach the point of being able to manufacture such specific devices? ... The trouble is that a socket (such as that in an enzyme or a transport protein) that can recognise another molecule is much more difficult to engineer than the molecule itself. ... So what were the control techniques? How was tarry chaos avoided? If the enzymes in today's cells can cope so well this is partly because the molecules that they come across belong to a quite limited set. An enzyme may distinguish between D- glucose and D-fructose, because these are among the relatively few kinds of molecules that it encounters: but it can easily be confused by molecules from a larger range. ... A primitive organism, lacking such customs control and living in a tarry `broth' that contained for every `correct' molecule a myriad of similar `incorrect' ones would have to have far more accurate enzymes to bring about any particular sequence of reactions. So that is the problem: how to evolve accurate recognising structures from a molecular technology that probably could not tell glycine from alanine, let alone D from L. Until you know one molecule from another how do you start to do the kind of sophisticated chemistry needed to make the membranes, the active centres and so on, on which molecular discrimination depends?" (Cairns-Smith, 1982, pp.59-60).
"Was 'chemical evolution' the connection? I do not think so. The building up of a primordial soup, if such a thing ever happened, would have been part of environmental evolution. The oceans would have accumulated organic molecules in much the same way as any other geochemical process would have taken place. Unless you take a religious or mystical view there was no guiding hand to contrive an outcome suitable for the origin of life. Mountains were made and worn down, the wind blew, the sun shone - and a soup did or did not form: all such processes were on an equal footing; it would only have been with an eye to the future that some of these processes might have been given a special label and called 'chemical evolution'. Biological evolution, on the other hand, is special, as discussed in the opening pages of this book. Above all what makes it special is heredity. This is the great divide: either there is a long-term hereditary mechanism working or there is not. If there is not then there is no accumulation of 'know-how' as Kuhn (1976) put it: the survival or non-survival of some putative half-organism will not be 'remembered' in the distant future to have any effect. Things would change, systems such as coacervates would come and go, but you could not expect them to become more efficient: you would not expect them to become more efficient at organic chemical operations, for example. Only evolving organisms can progress in that sort of way. Suppose that by chance some particular coacervate droplet in a primordial ocean happened to have a set of catalysts, etc. that could convert carbon dioxide into D- glucose. Would this have been a major step forward towards life? Probably not. Sooner or later the droplet would have sunk to the bottom of the ocean and never have been heard of again. It would not have mattered how ingenious or life-like some early system was; if it lacked the ability to pass on to offspring the secret of its success then it might as well never have existed." (Cairns-Smith, 1982, pp.69-70).
"There are two counter-intuitive aspects here. Using higher animals as models we would be much more inclined to see the organism as dynamic and the environment as static. But the only bit of an organism that is unambiguously not part of the environment is the bit that is static - the genotype. The other counter-intuitive idea is that, in computer jargon, it is software in organisms that lasts, while hardware is being perpetually replaced. Consider, for example, the instructions about how to make cytochrome c molecules: that software has remained little altered in essentials while mountain ranges have risen and been worn away many times. Yet the hardware, the actual individual protein molecules, individual DNA molecules, and so on, have been quite evanescent, flickering in and out of existence on a geological time scale. And this is very close to the heart of the problem ... we might say that life can begin to appear when mechanisms exist for retaining and propagating a kind of software - genetic information - indefinitely." (Cairns-Smith, 1982, p.80).
"Perhaps the simplest kinds of organisms would be hardly more than pieces of unencumbered information-printing machinery - `naked genes' as they have been called (Muller, 1929). To have the potential for indefinite evolution into the future, the potential information capacity of these naked genes would have to be very high. ... the idea of a 'naked gene', as the simplest and first kind of organism, has a long history. It is somewhat out of favour now mainly on account of two kinds of argument that are put up against it. First, there is a practical argument. Even if it could evolve in principle, it is said, such a structure would be too improbable in practice: it would be exceedingly unlikely to form, and the Earth would be exceedingly unlikely to continue to provide the highly specialised components needed to keep it replicating. If we think about a naked nucleic acid molecule such an attitude seems justified. Second, there is a formal argument. To evolve, a system must have both a genotype and a phenotype. Pure information is no use: it is the phenotype on which selection operates to give genetic information a meaning. Formally this argument is impeccable, but it is largely irrelevant. A `naked gene' would not be - could not be - pure genotype. Clearly what is meant by a gene, in this context at least, is some sort of structure that is holding information - something analogous to a DNA molecule or a punched card. Such a thing is not pure software as it includes the structure that is holding the information, and that is hardware. And at least some aspects of hardware could very well be phenotype." (Cairns-Smith, 1982, p.81).
"All such speculations that I have come across are evolutionary - they talk of the gradual perfection of this and that subsystem. But there is only one engine for the evolution of ingenious competence that I know of and that is natural selection. To evolve, the subsystems have to be part of an organism of some sort. Now there might be no need to postulate an earlier kind of life if some minimum nucleic acid-protein system could be conceived of as having formed spontaneously on the primitive Earth. But I do not see such a system as conceivable. You say yourself that naked nucleic acid genes are no good, and anything else would be more complicated - nucleic acid plus something else. I see no alternative to postulating some other kind of starter life to provide the milieu within which our kind of life system began its evolution." (Cairns-Smith, 1982, p.130).
"Biology has become, quite simply, the study of the causes and effects of evolution, and the question of the origin of life is, first, the question of the origin of evolution." (Cairns-Smith A.G., 1985, "Seven Clues to the Origin of Life: A Scientific Detective Story," Cambridge University Press: Cambridge UK, 1993, Reprinted, p.1).
"The optimism persists in many elementary textbooks. There is even, sometimes, a certain boredom with the question; as if it was now merely difficult because of an obscurity of view, a difficulty of knowing now the details of distant historical events. What a pity if the problem had really become like that! Fortunately it hasn't. It remains a singular case (Sherlock Holmes' favourite kind): far from there being a million ways in detail in which evolution could have got under way, there seems now to have been no obvious way at all. The singular feature is in the gap between the simplest conceivable version of organisms as we know them, and components that the Earth might reasonably have been able to generate. This gap can be seen more clearly now. It is enormous." (Cairns-Smith, 1985, p.4).
"Now I cannot deny all these possibilities: life on the Earth may be a miracle, or a freak, or an alien infection. And I agree that the confidence was misplaced that supposed in the fifties that the answer to the origin of life would appear in some footnote to the answer to the question of how organisms work. Something much more will be needed. Something odd." (Cairns-Smith, 1985, p.8).
"So please respect the humble bacterium that is playing this game. It can reproduce, it can evolve. E. coli must have some sort of long-term memory about how to make itself that can outlast its substance. That means that an E. coli must be an automatic factory containing something analogous to control tapes and automatic manufacturing equipment. And that is only part of it. All the equipment must be contained, organised, fed. Pieces for it to work on, energy to drive it, must be provided by the E. coli cell. Apart from the manufacturing machinery that can follow instructions, there has also to be another kind of machinery that instead reprints them - something analogous to a Xerox machine or a tape copier. All these things have to be contrived through the manufacturing machinery duly instructed by appropriate bits of the Library tape. It may seem hardly surprising that no one has ever actually made a self-reproducing machine, even though Von Neumann laid down the design principles more than 40 years ago. You can imagine a clanking robot moving around a stock-room of raw components (wire, metal plates, blank tapes and so on) choosing the pieces to make another robot like itself. You can show that there is nothing logically impossible about such an idea: that tomorrow morning there could be two clanking robots in the stock-room...(I leave it as a reader' home project to make the detailed engineering drawings.) There is nothing clanking about E. coli; yet it is such a robot, and it can operate in a stock-room that is furnished with only the simples raw components. Is it any wonder that E. coli's message tape is long? (... about 10 kilometres long.) Is it any wonder that no free-living organisms have been discovered with message tapes below '2 kilometres'? Is it any wonder that Von Neumann himself, and many others, have found the origin of life to be utterly perplexing?'" (Cairns-Smith, 1985, pp.14-15. Emphasis original).
"There are many thoughtful and knowledgeable people, nowadays, who don't understand the origin of life. This is in spite of a 'big picture' provided by a theory known as 'chemical evolution'. Like the phlogiston theory, 'chemical evolution' looks good from a distance, and there is a common-sense about it. But, to my mind, like the phlogiston theory, it fails to carry through an initial promise: it fails at the more detailed explanations." (Cairns-Smith, 1985, p.34).
"I will grant that the path of chemical evolution seems sensible and in the right direction. There are a few obvious puddles to be avoided and some of the flagstones are a bit uneven, perhaps. but there is the promise of an easy walk up to the foothills of the mountain that we can see straight ahead of us. It is a promise that is unfulfilled. The trouble with this path is that it leads us toward, but it does not lead us to expect, a sudden near-vertical cliff-face. Suddenly in our thinking we are faced with the seemingly unequivocal need for a fully working machine of incredible complexity: a machine that has to be complex, it seems, not just to work well but to work at all." (Cairns-Smith, 1985, p.37).
"It is true that some of the simpler amino acids have been found in complex mixtures generated under conditions simulating those that might have been present on the primitive Earth. Even nucleotide letters have been found in mixtures that are said to be plausible simulations of probiotic products. But all such 'molecules of life' are always minority products and usually no more than trace products. Their detection often owes more to the skill of the experimenter than to any powerful tendency for the 'molecules of life' to form." (Cairns-Smith, 1985, pp.44-45).
"Sugars are particularly trying. While it is true that they form from formaldehyde solutions, these solutions have to be far more concentrated than would have been likely in primordial oceans. And the reaction is quite spoilt in practice by just about every possible sugar being made at the same time - and much else besides. Furthermore the conditions that form sugars also go on to destroy them. Sugars quickly make their own special kind of tar - caramel - and they make still more complicated mixtures if amino acids are around." (Cairns-Smith, 1985, p.44).
"In sum the ease of synthesis of 'the molecules of life' has been greatly exaggerated. It only applies to a few of the simplest and in no case is it at all easy to see how the molecules would have been sufficiently unencumbered by other irrelevant or interfering molecules to have allowed further organisation to higher-order structures of the kinds that would be needed: message tapes, selective control structures, etc. Finally, even if ... primitive geochemistry had shown a precision in organic reaction control quite unlike modern geochemistry; even if it had produced all 'the molecules of life' and nothing but 'the molecules of life' in ample amounts; even then it would still only have reached the edges of the real problem ... Still, somehow, an evolving machine had to be made." (Cairns-Smith, 1985, p.44).
"Nucleotides and lipids have yet to be made under conditions that are realistic simulations of primitive Earth conditions. Nucleotides and lipids are much too complicated and particular for this to be surprising. They have all the appearance of molecules specially contrived for particular purposes. ... Perhaps you still feel that `time, and more time, and the resource of oceans' could have overcome the problems of how the more complex 'molecules of life' were originally made. I will now try to dispel such optimism by considering in more detail the most critical of all 'the molecules of life'. ... The Sigma Company is one of several that compete to supply biochemicals for research purposes. Looking through their catalogue I find that I can buy a gram of ATP - a primed ('wound-up') RNA nucleotide - for about £5. ATP is only as cheap as this because it is relatively easy to extract from bulk biological materials - horse meat to be more specific.The other three primed RNA nucleotides are about ten times the price, and the primed DNA nucleotides cost about £300 per gram. But even these are only as cheap as they are because they are derived from natural biological materials. As with postage stamps the price of nucleotides rises steeply with more abnormal types. The version of ATP with the sugar arabinose in the connector piece in place of ribose comes in at about £6000 a gram. But even such abnormal nucleotides, if they are synthetic (man-made) at all, are never wholly synthetic. Their manufacture will have started with components such as ribose obtained from biological sources. ... So £6000 a gram (or if you prefer £6M a kilogram) is a low estimate for the cost of a primed nucleotide 'in the open Universe' as it were. What would these materials cost if it were not for the horses (and others) that do most of the hard work? What would it actually cost to manufacture primed nucleotides from methane, ammonia and phosphate rock? I hate to think. Contrast glycine and alanine, the two simplest amino acids. These really can be said to be easily made-they have been detected frequently in complex mixtures from sparking experiments, in meteorites, etc. Glycine comes in at about 1p a gram, and alanine (as a mixture of 'left-handed' and 'right-handed' forms) about 8p. (I may say that at these prices you get 99% pure material; thunderstorm simulations give you 99% impure material.) Not only are they difficult to make, but primed nucleotides are rather unstable. Sigma recommend that the DNA primed nucleotides should be shipped in dry ice to avoid decomposition in transit, and nucleotides generally should be stored at below freezing point. Expensive and fragile, primed nucleotides (or unprimed ones for that matter) are, I think, implausible as significant geochemical products - as minerals - at any time." (Cairns-Smith, 1985, pp.45-46. Emphasis original).
"In Genetic Takeover I listed 14 major hurdles that would have to be overcome for primed nucleotides to have been made on the primitive Earth - from the build-up of sufficient and separate concentrations of formaldehyde and cyanide to the final 'winding-up' of the nucleotides. In practice each of these processes would be subdivided into separate unit operations that would have to be suitably sequenced. In carrying out an organic synthesis in the laboratory there are tens or hundreds of little events: lifting, pouring, mixing, stirring, topping-up, decanting, adjusting etc., etc. There may not be much to these unit operations in themselves, but their sequencing has to be right. There is a manufacturing procedure that has to be followed, and when such a procedure is at all prolonged it becomes absurd to imagine it being carried out by chance. That is why simple amino acids are plausible probiotic products, primed nucleotides are not. It is not that one cannot imagine plausible unit processes on the primitive Earth that, taken together, might have yielded primed nucleotides - as one can imagine a coin falling heads a thousand times in a row. Yes, you can imagine the primitive Earth doing the kinds of things that the practical organic chemist does. You can see a pool evaporating in the sun to concentrate a solution, or two solutions happening to mix because a stream overflows, or a catalytic mineral dust being blown in by the wind. you can imagine filtrations, decantations, beatings, acidifications: you can imagine many such operations taking place through little geological and meteorological accidents. But to show that each step in a sequence is plausible is not to show that the sequence itself is plausible. But, you may say, with all the time in the world, and so much world, the right combinations of circumstances would happen some time? Is that not plausible? The answer is no: there was not enough time, and there was not enough world. Let me try to justify this. It would be a safe oversimplification, I think, to say that on average the 14 hurdles that I referred to in the making of primed nucleotides would each take 10 unit operations - that at least 140 little events would have to be appropriately sequenced. (If you doubt this, go and watch an organic chemist at work; look at all the things he actually does in bringing about what he would describe as 'one step' in an organic synthesis.) And it is surely on the optimistic side to suppose that, unguided, the appropriate thing happened at each point on one occasion in six. But if we take this as the kind of chance that we are talking about, then we can say that the odds against a successful unguided synthesis of a batch of primed nucleotide on the primitive Earth are similar to the odds against a six coming up every time with 140 throws of a dice. Is that sort of thing too much of a coincidence or not? There are 6 possible outcomes from throwing a dice once; 6 x 6 from a double throw; 6 x 6 x 6 from a triple throw; and 6 multiplied by itself 140 times from 140 throws. This is a huge number, represented approximately by a 1 followed by 109 zeros (i.e. ~ 10109). This is the sort of number of trials that you would have to make to have a reasonable chance of hitting on the one outcome that represents success. Throwing one dice once a second for the period of the Earth's history would only let you get through about 1015 trials: so you would need about 1094 dice. That is far more than the number of electrons in the observed Universe (estimated at around 1080). Of course you might argue that in practice a synthesis might be carried through in different ways, and that is true, but remember what generous allowances we made in cutting down the actual amount of sheer skill that organic synthesis requires. And remember too that a manufacturing procedure is not usually very forgiving about arbitrary modifications: it all too easily goes off the rails never to recover. This is especially true of chemical processes, where it is usually not good enough to add the acid at the wrong time or throw away the wrong solution, or even use an ultraviolet lamp of the wrong sort. Careless organic synthesis only works when the product that is wanted belongs to that inevitably small set of molecules that are especially stable - molecules like carbon dioxide and water, even perhaps glycine and adenine in a much more limited way. But nucleotides are not like that to judge from the price. One's intuition can lead one astray when thinking of the role of vast times and spaces in generating improbable structures. The moral is that vast times and spaces do not make all that much difference to the level of competence that pure chance can simulate. Even to get 14 sixes in a row (with one dice following the rules of our game) you should put aside some tens of thousands of years. But for 7 sixes a few weeks should do, and for 3 sixes a few minutes. This is all an indication of the steepness of that cliff-face that we were thinking about: a three-step process may be easily attributable to chance while a similar thirty-step process is quite absurd." (Cairns-Smith, 1985, pp.46-48).
"In one way the eye is eminently understandable. It is so like a camera that you wonder why there is not a law suit going on somewhere for breach of patent. The dark box, the lens, the iris diaphragm, the light-sensitive surface - each of these components is there in each case. At deeper levels there are certainly patentable differences in design. The light-sensitive area at the back of the eye is not actually much like a film. It, and many other things about the eye, are not by any means fully understood. But what is eminently understandable about the eye is that it should consist of rather definite components working in collaboration: as remarked ... this is what really efficient pieces of machinery are usually like. The bit that is not so clear about the eye -and a favourite challenge to Darwin - is how its components evolved when the whole machine will only work when all the components are there in place and working. Not that this problem is peculiar to the eye. Organisms are full of such machinery, and it is a widely held view that this appearance of having been designed is the key feature of living things." (Cairns-Smith, 1985, p.58).
"Evolution started with 'low-tech' organisms that did not have to be, and probably were not made from 'the molecules of life'. The first part of this statement might seem rather obvious were it not for the baleful conclusion ... that the design of any conceivable organism is inevitably very very complicated - with robot machines that can make other machines (including ones like themselves) under instructions held in an information store that can be replicated by means of yet more machinery whose construction is also specified in the information store and can be executed by the robot machines... But that was another Big Red Herring. It arose from the unstated assumption that you actually need any machinery at all in an organism. Once you think you will need any, then you will think that you need a lot. If, for example, the organism has to have some kind's of printing machinery in it, so that it can replicate its genetic information, then it will need manufacturing machinery also to make this printing machinery. And then this manufacturing machinery, some sort of robot, must also be able to make other machines exactly like itself. The circle closes eventually, but not until after a long journey - too long to be a practicable piece of engineering even for us, and much too long for Nature before its engineer, natural selection, had come on the scene." (Cairns-Smith, 1985, pp.65-66. Emphasis original).
"So why start on such a journey? Only the messages are in principle essential for evolution, although in practice there has to be a material to hold the messages and physical means for their replication. But the components for making the genetic material can be provided by the environment and so can any machinery that is needed to work with these components to bring about the replication of the messages. An organism need be no more than a naked gene if the environment is kind enough. ... But does this not simply shift the difficulty from the organism to the environment? Certainly it shifts the difficulty, but it does not simply shift the difficulty. The difficulty changes, and it becomes much less severe. There do not have to be robots anywhere. The environment might possibly have to provide some sort of printing or replicating machinery, but it would not have to provide another instructable machine to make such machinery. Indeed it is a matter to be decided whether the environment would even have to provide anything that could be called replicating machinery, or machinery of any sort. There would be but three things that an environment would have to provide for 'naked genes': (i) material units out of which new genes could be made (by template replication); (ii) conditions that would allow this to happen (whether or not these conditions included any sort of replication machinery); and (iii) reasons why some genes should do better than others (what are called selection pressures). It is true that now for RNA, the material units are probably too complex as primitive Earth products; and it looks as if a big enzyme has indeed to be included under (ii). But these are incidental features, not vital. They are specific objections to RNA. They depend on particular attributes of RNA molecules - and, anyway, we had decided in the last chapter that neither RNA nor DNA was the original genetic material." (Cairns-Smith, 1985, pp.66-67. Emphasis original).
"A particular trouble with organic molecules is that they only self-assemble properly when they are fairly large. Only then will there be a sufficient overall cohesion between the molecules, or between the parts of a foldable molecule. (A soap molecule needs to have a long tail; a protein chain has to have some twenty units in it before it will start to fold up coherently.) But large molecules are difficult to come by, especially at the kinds of concentration and purity needed for precise self-assembly processes. The massive objections that there are to the idea that good supplies of nucleotides could have been pre-arranged by the primitive Earth ... apply with a similar force to almost any organic molecule of that sort of size - the sort of minimum size needed for organic molecules to be able to self-assemble in water into higher-order structures." (Cairns-Smith, 1985, pp.72-73).
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