email - April 2001

Orgel and Eigen

Several months ago we received the email message below. We saved it until now because it fits well with our “Wizard of Ooze” parody. It gives us a chance to explore the problems of life evolving from slime.

Subject: The origin of life
Date: Tue, 09 Jan 2001 12:46:17 +0100
From: Claudio

Hello, I'm Claudio from Rome (Italy) and, first of all, forgive my bad English.

I'm fond of scientific debate, especially referred to the origin of life and the appearance of mankind on our planet. Unfortunately, in Italy, the theory of evolution is fully dominant in the schoolbooks and in the common thought of people too. But let's go to my question, arisen from a polemical exchange of messages in a newsgroup dedicated to scientific and religious discussion.

Responding to my sentence ("there is not any scientific evidence that life came spontaneously and, until now, abiogenesis is to be considered impossible") two opponents, evolutionists, answered by quoting the studies of Orgel and Eigen. Particularly, they underlined important discoveries in the fields of "redondance of genetic information" and "prebiotic chemistry" that, in their opinion, demonstrate the validity of evolution, perfectly according to the darwinian theory.

I do not know anything about these discoveries and texts, because they are difficult to find in my country. Could you help me, if it is possible, describing the summary of these items and, mostly, your point of view about them?

With many thanks and my best wishes for your life and your wonderful web site



Let’s start with Orgel. Leslie E. Orgel works at the Chemical Evolution Laboratory, Salk Institute for Biological Studies, La Jolla, California. Here is a summary of his work, which we found on his web page.

The long-term goal of the research in my laboratory is to understand how a genetic system composed of nucleic acids could have come into existence on the primitive earth. We accept the "RNA World" hypothesis that states that our present DNA/RNA/PROTEIN world was preceded by a "biological" world in which RNA alone functioned both as a genetic material and as a source of functional enzymes (ribozymes). We are interested in studying a variety of polymerization reactions that may have played a role in the evolution of the RNA world.

We begin by stating the obvious. Orgel works at a Chemical Evolution Laboratory, where they certainly have made more than a casual investigation of possible ways that inanimate matter could have combined all by itself into something living. They do not claim to have found the answer. As we will see shortly, scientists have found “many scientific challenges1” that prevent dead matter from coming to life.

In our world, DNA contains instructions which the RNA reads to build the proteins that make up DNA and RNA. Clearly there is a “chicken or egg” circular dependency. Just as eggs come from chickens, and chickens come from eggs, proteins come from RNA, and RNA comes from proteins. Therefore, they are trying to prove the hypothesis that once upon a time RNA was able to reproduce itself without proteins.

Here is how the evolutionists describe the problem.

The first challenge on the path to a synthetic life form is to imagine a collection of molecules that is simple enough to form by self-assembly, yet sufficiently complex to take on the essential properties of a living organism. Any "stripping-down" of a present-day bacterium to its minimum essential components still leaves hundreds of genes and thousands of different proteins and other molecules. We must look to simpler systems if we hope either to synthesize a cell de novo or understand the origin of life on Earth. The search for simpler forms of life led to the "RNA world" hypothesis in which primordial cells lacking protein synthesis use RNA both as the repository of "genetic" information and as enzymes that catalyse metabolism. … Although there is considerable debate about the nature of the first genetic polymers, there is no doubt that RNA and DNA are the only currently practicable genetic materials for directed evolution in vitro. … But a replicase molecule by itself is not living, for two reasons. First, a single molecule could not actually replicate, as it cannot be both template and polymerase at the same time. Replication requires two RNA molecules--a replicase that acts as the polymerase, and another molecule, which could be either an unfolded replicase or an RNA complementary in sequence to the replicase, to act as a template. 2

The first experimental challenge is the evolution or design of an RNA replicase. Early attempts to derive an RNA replicase from the natural group I self-splicing introns produced ribozymes that could direct the assembly of oligonucleotide substrates on a template, and even the assembly of full-length RNA strands complementary to the ribozyme itself. The low efficiency of the reaction, however, even when driven by vast substrate excess, suggested that it was probably essential to use activated nucleotides, such as nucleoside triphosphates, to provide an energetic driving force for polymerization. The use of oligonucleotide substrates would also make it difficult or impossible to maintain a high concentration of all the different substrates needed for the replicase to mutate and evolve. No natural ribozymes are known that can catalyse the required chemistry and use nucleoside triphosphates as substrates. 3 [emphasis supplied]

It is impossible to foresee all the problems, but some are already clear. Most obviously, both replication cycles must operate under a single consistent set of conditions. Many ribozymes have optimal activity in the presence of high concentrations of divalent metal ions. In such conditions, vesicles composed of acidic phospholipids would aggregate, possibly interfering with growth and division. … These experimental possibilities could provide fascinating insights into what is now a complete black box of early evolution.4 [emphasis supplied]

As you can see from the quotes above, evolutionists find themselves up against a brick wall when it comes to figuring out a way that RNA molecules could reproduce all by themselves. So, despite what Orgel says on his web page, he is looking at molecules other than RNA that might have been the first self-reproducing molecules. Specifically, he is looking at threose-based nucleic acid (TNA). He has

explored in a systematic way the chemistry of DNA and RNA analogs with a modified backbone that, at least in principle, might be alternative genetic material for Earth's earliest organisms. Identification of nucleic acid analogs that could have been synthesized under the chemical (prebiotic) conditions on Earth that preceded the appearance of the earliest life forms may shed light on the origin of life. To this end, Eschenmoser and his co-workers (1) report on page 1347 of this issue the synthesis of an RNA analog that, in principle, could be an alternative genetic material for primitive life forms. 5

In other words, he is looking at molecules that are similar to DNA and RNA that might have been the first self-reproducing molecule. Since it is unquestionably true that life cannot originate in the current environment on Earth, he postulates the usual “soup on the primitive Earth.6” Remember that there is no evidence that such a soup ever existed, except for the belief that life evolved, and would have needed such an environment to evolve. Given these presumed conditions, Orgel believes that TNA would be more likely to form spontaneously.

Tetrose sugars with their four-carbon ring structure could be more readily synthesized in a prebiotic world than the pentose sugars of DNA and RNA because they can be assembled directly from two identical two-carbon fragments-for example, from two glycolaldehyde molecules. Pentose sugars are assembled in a more complicated way by combining two- and three-carbon fragments and would have been formed in complex mixtures along with tetroses and hexoses.7

So, it would have been easier for these molecules to form, if those conditions had actually existed. Interestingly, his very next sentence makes it seem irrelevant even if they did. He says,

Nucleotides containing a tetrose sugar have not been considered likely components of an early genetic polymer because they cannot be joined together by phosphate groups to give a backbone with a six-atom repeat.8

In other words, if a self-replicating four-atom molecule had formed first, there is no known way that it could change into RNA. Then, in his very next sentence, Orgel tries to wiggle out of this difficulty.

However, the discovery that a six-atom repeat is not an essential feature of early genetic material led to the realization that one of the tetrose sugars, threose, might form the basis for polymers with a five-atom repeat and a stereochemistry compatible with that of RNA.9

Later, however, he admits,

In the alternative gradualist scenario, ribonucleotides were at first substituted a few at a time and at random in TNA sequences. The proportion of RNA components increased over time from almost zero to 100%. The information present originally in the TNA sequence was, at least in part, preserved in the final RNA sequence. This attractive theory suffers from one major drawback. Introduction of a substantial number of ribonucleotides at random might not prevent replication of TNA, but it would almost certainly destroy the catalytic function of any particular TNA sequence and thus would render evolved TNA sequences useless when rewritten accurately as RNA.10 [emphasis supplied]

In other words, there are no life forms existing today that contain any TNA. Therefore, all of the TNA had to evolve into RNA and DNA. This seems remarkable to us. Think about it. The molecules that originally created life are completely absent from life today.

Furthermore, from what Orgel knows about organic chemistry, he believes that if TNA did mutate into RNA, the sequences would be “useless.” Despite this, his scientific observation is replaced by wishful thinking in his very next statement.

This flaw may not be fatal. The power of natural selection is easily underestimated, and it is possible that selection could find a "continuous" pathway from TNA to RNA in which the catalytic function of TNA was maintained.11

The problem, he says, is that we underestimate the power of natural selection. If we just believed more, then we would have the faith to accept the idea that mutation and natural selection can find a way to convert TNA to RNA. It is true that twenty-first century scientists aren’t smart enough to figure out how it could possibly happen, but natural selection is smarter than we are. Not only that, natural selection is even smart enough to “cover its tracks” by causing all the original TNA life forms, and all the intermediate TNA/RNA life forms to become extinct without a trace.


Eigen has developed some “glass bead games” that allegedly show how populations evolve. But our “six page newsletter” is already twelve pages long this month, so we will have to address that part of Claudio's email next month.

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1 Szostak, et al., Nature, Vol. 409, 18 January 2001, “Synthesizing Life” page 387 (Ev)
2 Ibid. page 387
3 Ibid. page 388
4 Ibid. page 390
5 Orgel, Science, 2000 Nov. 17, 290: 1306-1307 “ORIGIN OF LIFE: Enhanced: A Simpler Nucleic Acid” (Ev)
6 Ibid.
7 Ibid.
8 Ibid.
9 Ibid.
10 Ibid.
11 Ibid.