Friday, October 06, 2006

Origin of life: The molecular biologist's dream (or nightmare?!)

Here is a quote by leading origin of life researcher Leslie Orgel on the ten steps (minimum) to get from non-living chemicals to the first population of living organisms,

[Graphic: double- stranded RNA model, Indigo® Instruments]

from where "natural selection takes over" (step numbers in square brackets are mine):

"THE MOLECULAR BIOLOGISTS' DREAM The RNA-first scenario for the origin of the RNA World that we have described as the `Molecular Biologists' Dream' (Joyce & Orgel, 1999) can be strung together from optimistic extrapolations of the various achievements of prebiotic chemistry and directed RNA evolution described above. First we suppose that [1] nucleoside bases and [2] sugars were formed by prebiotic reactions on the primitive Earth and/or brought to the Earth in meteorites, comets, etc. Next, [3] nucleotides were formed from prebiotic bases, sugars, and inorganic phosphates or polyphosphates, and [4] they accumulated in an adequately pure state [5] in some special little `pool.' [6] A mineral catalyst at the bottom of the pool-for example, montmorillonite-then catalyzed the formation of long single-stranded polynucleotides, some of which were then converted to complementary double strands by template-directed synthesis. In this way [7] a library of double-stranded RNAs accumulated on the primitive Earth. We suppose that among the double-stranded RNAs there was [8] at least one that on melting yielded a (single-stranded) ribozyme capable of copying itself and its complement. Copying the complement would then have produced a second ribozyme molecule, and then repeated copying of the ribozyme and its complement would have lead to an exponentially growing population. In this scenario this is [10] where natural selection takes over. Darwin suggested that all life is descended from one or a few simple organisms that evolved on the Earth long ago. According to the more radical scenario of the Molecular Biologists' Dream, the whole biosphere descends from one or a few replicating polynucleotides that formed on the primitive Earth about four billion years ago. Of course, there are still a few problems in prebiotic chemistry that must be solved before the Dream can be turned into a convincing theory! In addition, [9] a plausible prebiotic mechanism for keeping together ribozymes and the products of their activity, for example, enclosure within a membrane, must be demonstrated ..." (Orgel, L.E., "Prebiotic Chemistry and the Origin of the RNA World," Critical Reviews in Biochemistry and Molecular Biology, Vol. 39, No. 2, pp.99-123. Emphasis original).

Two other leading origin of life theorists, Christopher Wills and Jeffrey L. Bada, comment on this "molecular biologists' dream," i.e. "the ability to self-replicate," that "these evolved" [sic] "ribozymes are still a very long way from the full realization of the molecular biologists' dream" as "Even the cleverest ribozyme yet produced can only copy short stretches of itself" and "It is very unlikely, we suspect, that a molecule can be selected for that could polymerize a copy of itself along its entire length without some kind of help" (my emphasis):

"It is this last function, the ability to self-replicate, that Joyce and Orgel call `the molecular biologists' dream:' If a truly self-replicating molecule could be produced in the laboratory, a huge gap in our understanding of the origin of life would be closed. Joyce is sanguine about this possibility, because he is most impressed by the ability of evolution in the test tube to generate ribozymes with new functions. Remarkable as the results from test-tube-evolution experiments are, these evolved ribozymes are still a very long way from the full realization of the molecular biologists' dream. Even the cleverest ribozyme yet produced can only copy short stretches of itself. It is very unlikely, we suspect, that a molecule can be selected for that could polymerize a copy of itself along its entire length without some kind of help. ... Let us assume for a moment that Orgel is correct and that sometime in the near future a researcher will tease out, from the large array of random RNA sequences lurking in a test tube, the one that has the ability to catalyze its own replication from simple components of the type found in the primordial soup. At this point, many researchers would argue that life has been created in the laboratory. But would this be a reenactment of the origin of life as it might have taken place on the early Earth? Certainly not! A much larger problem will remain: Even if researchers eventually do create such an astonishing molecule in the laboratory, this is no guarantee that a similar molecule would ever have been synthesized in the primordial soup or on rock surfaces early in the history of our planet." (Wills, C.J. & Bada, J.I., "The Spark of Life: Darwin and the Primeval Soup," [2000], Oxford University Press: New York NY, 2001, reprint, pp.129-130)

Moreover, as Wills & Bada point out above, even if "a researcher" does "tease out, from the large array of random RNA sequences lurking in a test tube, the one that has the ability to catalyze its own replication from simple components of the type found in the primordial soup," there is "no guarantee that a similar molecule would ever have been synthesized in the primordial soup or on rock surfaces early in the history of our planet."

Although Wills and Bada do not say why it would not, presumably their reason is the same given by astrobiologist Robert Shapiro, that "The concept that the scientists are illustrating is one of intelligent design" since "No better term can be applied to a quest in which chemists are attempting to prepare a living system in the laboratory, using all the ingenuity and technical resources at their disposal":

"It is probably only a matter of time, to be measured in years rather than decades, before a self-sustained RNA evolving system can be demonstrated in the laboratory. This would be a case in which a DNA-and protein-based life form, namely a human biochemist, gives rise to an RNA-based life form, an interesting reversal of the sequence of events that occurred during the early history of life on Earth.' When that event takes place, the media will probably announce it as the demonstration of a crucial step in the origin of life. I would agree, with one modification. The concept that the scientists are illustrating is one of intelligent design. No better term can be applied to a quest in which chemists are attempting to prepare a living system in the laboratory, using all the ingenuity and technical resources at their disposal. Whether they use synthetic chemicals or materials isolated from nature, we would be justified in calling the living system artificial or human-made life. (Shapiro, R., "Planetary Dreams: The Quest to Discover Life beyond Earth," John Wiley & Sons: New York NY, 1999, pp.102-104. My emphasis)

Another eminent origin of life theorist, A.G. (Graham) Cairns-Smith, listed "14 major hurdles that would have to be overcome for primed nucleotides to have been made on the primitive Earth" (i.e. only for steps 1-3 above) and "In practice each of these processes would be subdivided into separate unit operations that would have to be suitably sequenced" such that "on average the 14 hurdles ... in the making of primed nucleotides would each take 10 unit operations - that at least 140 little events would have to be appropriately sequenced":

"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 A.G., "Seven Clues to the Origin of Life: A Scientific Detective Story," [1985], Cambridge University Press: Cambridge UK, 1993, reprint, pp.46-48).

As Cairns-Smith pointed out above, "to show that each step in a sequence is plausible is not to show that the sequence itself is plausible" (my emphasis), e.g. "a three-step process may be easily attributable to chance while a similar thirty-step process is quite absurd," and that for the equivalent of steps 1-3 above, concluded that "there was not enough time, and there was not enough world" that "the right combinations of circumstances would happen."

That "all of these events be linked together" Shapiro likens to "the idea that the golf ball could play its own way around" "a difficult course at well under par" "without the golfer"!:

"The search for ribozymes evokes the same feeling of achievement and beauty in me that I get when I see a skilled golfer playing a difficult course at well under par. To imagine that related events could take place on their own appears as likely as the idea that the golf ball could play its own way around the course without the golfer. We can, of course imagine that natural forces would lend a helping hand. A hurricane could move the ball down the course, and occasional floods might `putt' the ball into the hole. A small earthquake could then remove it and place it on the next tee. Perhaps each of these events could be simulated if we tried hard enough. But to insist that all of these events be linked together and move in an appropriate direction puts our origin into the realm of Morowitz's odds [10100,000,000,000 to 1]." (Shapiro, Ibid, p.104. My emphasis and parenthesis)

Now I actually agree, on the basis of the evidence of the universal presence of RNA in the most fundamental molecular machinery of life, such as, "ribosomes, the complex assembly of macromolecules which are the actual site of protein synthesis, are made of several structural RNA molecules," "The molecules which act as the interface between the amino acid and the triplet of bases associated with it are also made of RNA ... tRNA (for transfer RNA)" and "the cell ... For working purposes ... makes ... RNA copies of selected parts of the DNA" called "messenger RNA":

"RNA is very similar to DNA. Instead of the sugar deoxyribose, it has just plain ribose (hence the name RiboNucleic Acid), which has an -OH group whose deoxyribose has an -H one. Three of the four bases (A, G and C) are identical to those in DNA. The fourth, Uracil (U), is a close relative of Thymine (T), since thymine is just uracil with a -CH3 group replacing an -H group. This has little effect on the base-pairing. U can pair with A, just as, in DNA, T pairs with A. RNA might be described as using the same language as DNA but with a different accent. RNA can form a double helix, similar but not quite identical to the DNA double helix. It is also possible to form a hybrid double helix which has one chain of RNA and one of DNA. By and large, long RNA double helices are rare, RNA molecules being typically single-stranded, though often folded back on themselves to form short stretches of double helix. In modern organisms we find RNA used for three purposes. For a few small viruses, such as the polio virus, it is used instead of DNA as the genetic material. Some viruses employ single-stranded RNA; a few use it double-stranded. RNA is also used for structural purposes. The ribosomes, the complex assembly of macromolecules which are the actual site of protein synthesis, are made of several structural RNA molecules, assisted by several tens of distinct protein molecules. The molecules which act as the interface between the amino acid and the triplet of bases associated with it are also made of RNA. This family of RNA molecules, called tRNA (for transfer RNA), are used to carry each amino acid to a ribosome, where it will be added to a growing polypeptide chain which will, when complete, become a folded protein. The third and perhaps the most important use the cell makes of RNA is as messenger RNA. The cell does not use the DNA itself for everyday work but instead keeps it as the file copy. For working purposes it makes many RNA copies of selected parts of the DNA. It is these tapes of messenger RNA which direct the process of protein synthesis on the ribosomes, using the genetic code ..." (Crick, F.H.C., "Life Itself: Its Origin and Nature", Simon & Schuster: New York NY, 1981, pp.174-175)

that the origin of life was most probably of double- stranded RNA (see my Yahoo group posts of 24-Mar-05 & 27-Mar-05 and a section of my future book "Progressive Creation"). That is, I accept, on the basis of the biomolecular evidence, that there was an RNA world in which these 10 steps of Orgel's Molecular Biologists Dream (or is that Nightmare?!) which included conservatively hundreds of sub-steps, all in the right sequence, actually occurred.

However, also on the basis of the evidence that not even one of these above ten steps has been shown to occur fully naturalistically in a plausible early Earth scenario (e.g. without the input of human intelligent design) and in fact for steps 1-3 alone "there was not enough time, and there was not enough world" that "the right combinations of circumstances would happen," I therefore conclude that the origin of life via this RNA world was at least what Christian philosopher/ theologian Norman L. Geisler calls a "second class miracle," i.e. a "supernaturally guided event ... whose natural process can be described scientifically (and perhaps even reduplicated by humanly controlled natural means)":

"It may be that some things are so highly unusual and coincidental that, when viewed in connection with the moral or theological context in which they occurred, the label `miracle' is the most appropriate one for the happening. Let us call this kind of supernaturally guided event a second class miracle, that is, one whose natural process can be described scientifically (and perhaps even reduplicated by humanly controlled natural means) but whose end product in the total picture is best explained by invoking the supernatural. Providing that the theist can offer some good reasons (by virtue of the moral or theological context of the event) for not accepting a purely natural explanation, then there is no reason to rule out the evidential value of such unusual natural events." (Geisler, N.L., "Christian Apologetics," [1976], Baker: Grand Rapids MI, Ninth Printing, 1995, p.277)

Stephen E. Jones, BSc (Biol).
Genesis 4:25-26. 25Adam lay with his wife again, and she gave birth to a son and named him Seth, saying, "God has granted me another child in place of Abel, since Cain killed him." 26Seth also had a son, and he named him Enosh. At that time men began to call on the name of the LORD.