Sunday, May 14, 2006

Re: origin of life `chicken and egg problem' : What about the RNA World?

AN

Thanks for your message, which as is my normal practice with questions on a creation/ evolution/ design topic, I am copying to my blog CED, minus your identifying information.

[Graphic: RNA ribozyme ribbon diagram, "Exploring the New RNA World," by Thomas R. Cech.]

I have a long-standing policy not to get involved in private discussions on creation/evolution/design issues, so please don't interpret the comprehensiveness of this response as being an invitation to debate, because it is not. The fullness of my response is mainly for readers of my blog.

----- Original Message -----
From: AN
To: Stephen E. Jones
Sent: Friday, May 12, 2006 7:08 PM
Subject: RNA world

AN>Dear Mr Jones,
>
I have read your article on one of your sites, namely Creation/Evolution Quotes: Origin of Life #1: "... raises a question which is as yet unanswerable"

That page, "Creation/Evolution Quotes: Origin of Life #1" was last updated in 10 December, 2003. I had always intended to classify my quotes as I posted them, but due to completing a biology degree from 2000-2004, I was unable to do so. Most of my 6+ megabytes of quotes online are under Unclassified quotes.

However, I recently announced that I have decided to publish my quotes in an `Evolution Quotes Book' which will probably be a self-published eBook. As of yesterday I had added 881 quotes in 262 pages. On current projections my book will be 8,939 quotes in 2,658 pages, so after a little more than a month I am 10% there! But I expect (and hope!) that after eliminating duplicates and less important quotes as I get to them, that the eBook will end up being less than half that, i.e. ~4,000 quotes in ~1,200 pages, which will be over 3 or 4 volumes.

AN>I do not think the "chicken and egg problem" is still valid according to the present knowledge about origin of life. What about RNA World hypothesis?

To make the heading more informative, I have turned your question into a statement, using as many of your words as I could. I don't have time to answer your question in detail, so I will just post quotes that I have classified to date relevant to the "RNA World hypothesis" under rough headings in Chapter 19, "Origin of Life"

19.16.8. Nucleic acids (RNA & DNA)
a. Sugars
i. Ribose sugar is unstable and so would not have been sufficiently prevalent under prebiotic conditions

"The origin of sugars, including ribose, seems readily explicable by the prebiotic functioning of the formose reaction ... In fact we are dealing here with a complex network of reactions, producing sugars from pre-existing sugars and formaldehyde ... There are two problems with this network that should be mentioned. First, the sugars formed are rather unstable, so, if they are to be present in significant amounts, this can only be in a steady state of formation and decay. It is imperative, therefore, that the end products of sugar decay be recycled to formaldehyde. Second, it is not at all obvious how ribose, among the more than 40 sugars could have been sufficiently prevalent under prebiotic conditions." (Maynard Smith, J. & Szathmáry, E., "The Major Transitions in Evolution," W.H. Freeman: Oxford UK, 1995, pp.30-31).

ii. Precursors have to be far more concentrated than would have been likely in primordial oceans
(1) Interfering cross-reactions with other sugars formed and amino acids

"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, A.G., "Seven Clues to the Origin of Life: A Scientific Detective Story," Cambridge University Press: Cambridge UK, 1993, reprint, p.44).

b. Nucleotides
i. Synthesis of nucleosides (base and sugar linked) also poses problems
(1) Purines react with ribose to yield the corresponding nucleosides in small amounts, and the analogous reaction with pyrimidines seems hopeless

"Setting aside the problem of the origin of ribose, the synthesis of nucleosides (base and sugar linked together as in present-day nucleotides) also poses problems. Purines react with ribose to yield the corresponding nucleosides in small amounts. The analogous reaction with pyrimidines seems hopeless. The phosphorylation of nucleosides to nucleotides can be done in dry-phase with relatively good yield, but all sorts of isomers with varying degrees of phosphorylation emerge. This lack of purity is important because accurate replication of a polymer depends on chemical purity." (Maynard Smith, J. & Szathmáry, E., "The Major Transitions in Evolution," W.H. Freeman: Oxford UK, 1995, pp.31-32).

ii. Phosphorus
(1) No one has yet come up with a satisfactory explanation of how phosphorus, which is a relatively rare substance in nature, became such a crucial ingredient in RNA (and DNA)

"But as researchers continue to examine the RNA-world concept closely, more problems emerge. How did RNA arise initially? RNA and its components are difficult to synthesize in a laboratory under the best of conditions, much less under plausible prebiotic ones. For example, the process by which one creates the sugar ribose, a key ingredient of RNA, also yields a host of other sugars that would inhibit RNA synthesis. Moreover, no one has yet come up with a satisfactory explanation of how phosphorus, which is a relatively rare substance in nature, became such a crucial ingredient in RNA (and DNA)." (Horgan, J., "In The Beginning...," Scientific American, February 1991, p.103. Ellipses original).

[...]

19.18.6. Nucleic acid (RNA/DNA) first (including RNA world)
a. RNA synthesis

i. How did RNA arise initially?
(1) RNA and its components are difficult to synthesize in a laboratory under the best of conditions, much less under plausible prebiotic ones

"But as researchers continue to examine the RNA-world concept closely, more problems emerge. How did RNA arise initially? RNA and its components are difficult to synthesize in a laboratory under the best of conditions, much less under plausible prebiotic ones. For example, the process by which one creates the sugar ribose, a key ingredient of RNA, also yields a host of other sugars that would inhibit RNA synthesis. Moreover, no one has yet come up With a satisfactory explanation of how phosphorus, which is a relatively rare substance in nature, became such a crucial ingredient in RNA (and DNA)." (Horgan, J., "In The Beginning...," Scientific American, February 1991, p.103. Ellipses original).

ii. Routes too artificial

(1) Unlikely that they ever took place on the early Earth

"At first glance, this doesn't really seem to be too much of a problem. An RNA nucleotide is made up of a phosphorylated ribose sugar linked to one of the four RNA bases, and a variety of plausible prebiotic synthetic routes for creating all of these have been suggested. For instance, one of the simplest prebiotic methods for creating ribose is the polymerisation of formaldehyde. Adenine can be formed from ammonia and hydrogen cyanide, as can guanine. Cytosine can be formed by reacting cyanoacetylene with cyanate, cyanogen or urea, and uracil can be produced by the hydrolysis of cytosine. But would these kinds of reactions have been plausible on the early Earth? One scientist who thinks not is Robert Shapiro at New York University, US. He argues that many of the prebiotic routes suggested for the synthesis of nucleotide bases are so artificial that it is unlikely that they ever took place on the early Earth, and that, even if they did, any yields from the reactions would have been so small and the products would have decayed so rapidly that there would have been little chance of them getting together to form nucleotides." (Evans, J., "It's alive - isn't it? ," Chemistry in Britain, Vol. 36, No. 5, May 2000, pp.44-47, p.46).

iii. Yields too small and would have decayed too rapidly
(1) Little chance of them getting together to form nucleotides

Same quote above "At first glance ...".

b. RNA chains too short

i. Only a few nucleotides have joined together before the RNA chain snaps

"If early life was based on RNA, then the first ribozymes must initially have formed abiotically on the early Earth before going on to help form the first lifeforms. Researchers propose that these first RNA sequences must have been produced by the gradual stringing together of individual nucleotide building blocks of RNA that arose naturally in the environment. When this has been attempted in the laboratory, only a few nucleotides have joined together before the RNA chain snaps - far short of the 50 nucleotides that would be needed before a sequence could show any kind of catalytic activity." (Evans, J., "It's alive - isn't it?" Chemistry in Britain, Vol. 36, No. 5, May 2000, pp.44-47, p.46).

c. RNA replication

i. Can make copies of itself only with a great deal of help from the scientist
(1) Experiments simulating the RNA world are too complicated to be plausible scenarios

"Once RNA is synthesized, it can make new copies of itself only with a great deal of help from the scientist, says Joyce of the Scripps Clinic, an RNA specialist. `It is an inept molecule,' he explains, `especially when compared with proteins.' Leslie E. Orgel of the Salk Institute for Biological Studies, who has probably done more research exploring the RNA-world scenario than any other scientist, concurs with Joyce. Experiments simulating the early stages of the RNA world are too complicated to represent plausible scenarios for the origin of life, Orgel says. `You have to get an awful lot of things right and nothing wrong,' he adds." (Horgan, J., "In The Beginning...," Scientific American, February 1991, p.103. Ellipses original).

d. RNA ribozymes
i. Make only minor changes

"Exactly what form that self-replicating enzyme might have taken was first suggested 30 years ago, when RNA was put forward as the precursor to DNA and proteins in early lifeforms. In cells today, RNA is the go-between for DNA and proteins: a protein is manufactured from an RNA template, which has itself been created from a DNA template. The idea remained purely speculative until the early 1980s when Thomas Cech at the University of Colorado and Sydney Altman at Yale University independently discovered RNA molecules with catalytic ability, now known as ribozymes. This discovery immediately put on a much firmer footing the idea that RNA could have been used for both storing information and catalysing reactions in early forms of life, and in 1986 the term 'RNA world' was coined. Nevertheless, despite the fact that most scientists working in this field accept the validity of the idea, the RNA world hypothesis is still far from being proved. For one thing, in almost 20 years only seven types of natural ribozymes have been discovered: two remove introns (parts of RNA that don't code for proteins) from themselves; four cut themselves in two; and one trims off the end of an RNA precursor." (Evans, J., "It's alive - isn't it?," Chemistry in Britain, Vol. 36, No. 5, May 2000, pp.44-47, p.44)

ii. Not one self-replicating RNA has emerged to date

"DNA replication is so error-prone that it needs the prior existence of protein enzymes to improve the copying fidelity of a gene-size piece of DNA. `Catch-22,' say Maynard Smith and Szathmáry. So, wheel on RNA with its now recognized properties of carrying both informational and enzymatic activity, leading the authors to state: `In essence, the first RNA molecules did not need a protein polymerase to replicate them; they replicated themselves.' Is this a fact or a hope? I would have thought it relevant to point out for 'biologists in general' that not one self-replicating RNA has emerged to date from quadrillions (1024) of artificially synthesized, random RNA sequences." (Dover, G.A., "Looping the evolutionary loop," Review of "The Origins of Life: From the Birth of Life to the Origin of Language," by John Maynard Smith and Eörs Szathmáry, Oxford University Press: Oxford UK, 1999. Nature, Vol. 399, 20 May 1999, pp.217-218).

I have many more quotes on the problems of the RNA world (these are only from my quotes of 1999-2001). But as it happened, I found another one yesterday, which I will add to my May 2006 Unclassified Quotes page, the important point being the last line, which is another chicken-and-egg problem, "It also raises an important difficulty for theories of the origin of life. The genome could not become greater than 100 bases in the absence of specific replication enzymes, yet a genome of less than 100 bases could hardly code for such an enzyme" (my emphasis):

The accuracy of replication If the replication process were exact, no new variants would arise, and evolution would slow down and stop. The _in vitro_ experiments work only because enzyme replication of RNA is not exact. However, evolution would also be impossible if the replication process were too inaccurate. Thus although an occasional error in replication, or mutation, may lead to an improvement in adaptation, most will lead to deterioration. Hence, too high an error rate will lead to loss of adaptation. I now try to make this idea quantitative. How accurate must replication be if adaptation is to be maintained? ... Equation 2.13 [Q ~ r/R] gives the critical value of Q, the accuracy of replication, if the adapted sequence, S, is to be maintained by selection against the deterioration caused by mutation. If the replication rate of the mutants is only slightly less than that of the optimal S sequence (i.e. weak selection), then the accuracy Q must be high, because the mutant particles compete with S for resources. What if mutants replicate slowly: in the extreme case, suppose they do not replicate at all? It does not follow that any degree of accuracy, however low, will be sufficient. Thus S particles will not be immortal: there will be some rate of destruction, or `death rate', even in the absence of competition from non-S particles. On average, each S particle must, during its life, produce one perfect S copy. Hence if the average number of copies per S particle before it is destroyed is R, then Q > 1/R is necessary. The critical accuracy, then, depends both on the success of non-S copies, and, if non-S particles have a low replication rate, on the average number of copies produced by an S particle during its lifetime. In practice, it seems unlikely that evolution would be possible if Q < 1/2. The practical implication of this is that it places a limit on the size of the genome, for any given replication accuracy. Thus consider a genome of n nucleotides, and let the probability that an error is made in replication be u per nucleotide. Then Q = (1 - u)n = e-nu. Hence the maintenance of adaptation requires, very approximately, that nu < 1. Three very different error rates exist: the rate for replication in the absence of enzymes, which may have occurred during the origin of life; the rate for replication of RNA, which does not involve a `proof-reading' stage; and the rate for the replication of DNA, with proof-reading. The values are, very approximately, as follows:
   error rate (u)
non-enzymic replication 1/10 - 1/100
RNA replication 10-3 - 10-4
DNA replication 10-9 - 10-10
The requirement that nu < 1 then explains the fact that the genome of RNA viruses is never greater than about 104 bases, and of higher organisms no greater than 109 bases. It also raises an important difficulty for theories of the origin of life. The genome could not become greater than 100 bases in the absence of specific replication enzymes, yet a genome of less than 100 bases could hardly code for such an enzyme: for further discussion of this problem, see Eigen et al. (1981), and Maynard Smith and Szathmary (1995)." (Maynard Smith, J., "Evolutionary Genetics," [1988], Oxford University Press: Oxford UK, 1998, Second edition, 2000, reprint, pp.20-24. Emphasis original)

So, that alone kills "the RNA World hypothesis," not that it ever was alive, according to leading origin of life theorists Joyce and Orgel in a chapter "Another Chicken-and-Egg Paradox" in a book titled "The RNA World":

"In the 1980s a scientist named Thomas Cech showed that some RNA has modest catalytic abilities. Because RNA, unlike proteins, can act as a template and so potentially can catalyze its own replication, it was proposed that RNA-not protein-started earth on the road to life. Since Cech's work was reported, enthusiasts have been visualizing a time when the world was soaked with RNA on its way to life; this model has been dubbed `the RNA world.' Unfortunately, the optimism surrounding the RNA world ignores known chemistry. In many ways the RNA-world fad of the 1990s is reminiscent of the Stanley Miller phenomenon during the 1960s: hope struggling valiantly against experimental data. Imagining a realistic scenario whereby natural processes may have made proteins on a prebiotic earth-although extremely difficult-is a walk in the park compared to imagining the formation of nucleic acids such as RNA. The big problem is that each nucleotide `building block' is itself built up from several components, and the processes that form the components are chemically incompatible. Although a chemist can make nucleotides with ease in a laboratory by synthesizing the components separately, purifying them, and then recombining the components to react with each other, undirected chemical reactions overwhelmingly produce undesired products and shapeless goop on the bottom of the test tube. Gerald Joyce and Leslie Orgel-two scientists who have worked long and hard on the origin of life problem-call RNA `the prebiotic chemist's nightmare.' They are brutally frank: `Scientists interested in the origins of life seem to divide neatly into two classes. The first, usually but not always molecular biologists, believe that RNA must have been the first replicating molecule and that chemists are exaggerating the difficulties of nucleotide synthesis.... The second group of scientists are much more pessimistic. They believe that the de novo appearance of oligonucleotides on the primitive earth would have been a near miracle. (The authors subscribe to this latter view). Time will tell which is correct. [Joyce G.F. & Orgel L.E., "Prospects for Understanding the Origin of the RNA World," in "The RNA World," Gesteland R.F. & Atkins J.F., eds. Cold Spring Harbor Laboratory Press, Cold Spring Harbor NY, 1993, p.19] Even if the miracle-like coincidence should occur and RNA be produced, however, Joyce and Orgel see nothing but obstacles ahead. In an article section entitled "Another Chicken-and-Egg Paradox" they write the following: `This discussion ... has, in a sense, focused on a straw man: the myth of a self-replicating RNA molecule that arose de novo from a soup of random polynucleotides. Not only is such a notion unrealistic in light of our current understanding of prebiotic chemistry, but it should strain the credulity of even an optimist's view of RNA s catalytic potential.... Without evolution it appears unlikely that a self-replicating ribozyme could arise, but without some form of self-replication there is no way to conduct an evolutionary search for the first, primitive self-replicating ribozyme. [Joyce & Orgel, 1993, p.13] In other words, the miracle that produced chemically intact RNA would not be enough. Since the vast majority of RNAs do not have useful catalytic properties, a second miraculous coincidence would be needed to get just the right chemically intact RNA." (Behe M.J., "Darwin's Black Box: The Biochemical Challenge to Evolution," Free Press: New York NY, 1996, pp.171-172)

The above quote is one of many in my online database of Unclassified Quotes that I have yet to get to, from 2002-2006.

AN>I will be grateful to hear from you.
Best wishes
>
>AN

But of course if one is a philosophical materialist/naturalist, the problems (indeed the evidence) of the origin of life does not matter. Then, along with the National Academy of Sciences, since: 1) life exists; and 2) unintelligent natural process is the only possibility; 3) "the question is no longer" (indeed never was, is not now, nor ever will be), "whether life could have originated by chemical processes involving nonbiological components", but only "which of many pathways might have been followed to produce the first cells":

"For those who are studying the origin of life, the question is no longer whether life could have originated by chemical processes involving nonbiological components. The question instead has become which of many pathways might have been followed to produce the first cells." ("Science and Creationism: A View from the National Academy of Sciences," National Academy Press: Washington DC, Second Edition, 1999, p.6)

Stephen E. Jones, BSc (Biol)
`Evolution Quotes Book'

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