The Search for Molecules Capable of Starting Evolution and Forming under Prebiotic Conditions:
Evidence for the Existence of God

Madhavendra Puri das
May 2005



Physicists believe that after the origin of the universe from the Big Bang, the most complicated configurations of matter were hydrogen atoms. After these hydrogen atoms condensed into stars, nuclear reactions generated larger atoms including carbon, nitrogen, oxygen, sulfur, and phosphorus. Before the formation of our solar system 4.5 billion years ago, these atoms combined to form simple molecules, such as formic acid, formaldehyde and glycolaldehyde, which are observed today in interstellar space by spectroscopy (1). (Throughout this article, a number in parenthesis represents a report in a scientific journal, which is listed in the bibliography at the end.) Another guide to the kinds of organic molecules existing when the earth formed is a class of meteorites called carbonaceous chondrites, which have been found to contain various categories of organic molecules, including amino acids, sulfonic acids, phosphonic acids, hydroxy acids, carboxylic acids, amines, amides, aliphatic hydrocarbons, aromatic hydrocarbons, sugars, alcohols, aldehydes, ketones, sulfur heterocycles and nitrogen heterocycles (2). Spark discharge or UV irradiation of simulated primordial atmospheres produces, at best, the same kinds of simple primordial molecules. The following websites show the structures of these molecules:

http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookCHEM2.html
http://www.sigmaaldrich.com/Area_of_Interest/The_Americas/United_States.html


No terrestrial or extraterrestrial path from these simple primordial molecules to the nucleic acids RNA or DNA has been discovered in fifty years of intense research at the world’s best universities. This is shown in detail below. Aside from nucleic acids, no one has succeeded in demonstrating under prebiotic conditions the formation of any kind of molecular system capable of starting evolution. Evolution in this beginning stage required self-replicating molecular systems that are able to undergo mutations. Without mutations, there is no variation upon which natural selection can work. A further constraint on evolution is that these mutable self-replicating systems were able to form under prebiotic conditions, which means conditions that existed before the first appearance of life.

Let us first examine nucleic acids. Since they are, in principle, able to form complementary copies of themselves, they are the natural first choice for mutable self-replicating systems. In order to understand complementarity, we need some background in the chemistry of nucleic acids. There are many websites on this, some of which have very good illustrations:

http://www.worldofmolecules.com/life/
http://www.answers.com/topic/nucleobase
http://prion.bchs.uh.edu/bp_type/bp_structure.html

http://www.imb-jena.de/IMAGE_BPDIR.html
http://www.accessexcellence.org/RC/VL/GG/basePair2.html
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/B/BasePairing.html
h
ttp://ndbserver.rutgers.edu/NDB/structure-finder/index.html

As described in these websites, ribonucleic acid (RNA) is a chain of ribonucleotides, each of which is composed of phosphate, the sugar ribose, and one of four nucleobases: adenine (A), guanine (G), cytosine (C) and uracil (U). The first two nucleobases are called purine nucleobases and the second two are called pyrimidine nucleobases. In deoxyribonucleic acid (DNA) the sugar deoxyribose replaces ribose, and the nucleobase thymine replaces uracil. Since both of these sugars possess five carbon atoms, they are called pentoses. A nucleotide without phosphate is called a nucleoside. A molecule consisting of a few nucleotides hooked together is called an oligonucleotide. An RNA oligonucleotide can be represented as a short chain of ribonucleotides: ACGAUUGCCG. The complement of this oligonucleotide is UGCUAACGGC. The complement is formed by replacing each A with a U and each G with a C. A is attracted to U and G is attracted to C. This means that, under ideal conditions, free nucleotides floating in a solution are attracted to their complements on an oligonucleotide. The complement of the complement of an oligonucleotide is the original oligonucleotide itself. In practice, as shown below, there are many impediments to nucleic acid replication by this process. The first major problem is synthesizing oligonucleotides under prebiotic conditions. This is discussed in detail in the next section.

Forces opposing prebiotic oligonucleotide formation

Chemist Stanley Miller, who achieved world-wide fame in the 1950s by performing spark-discharge experiments for the prebiotic production of organic compounds, has worked steadily in the field of prebiotic chemistry for fifty years and has published more than a hundred articles in professional peer-reviewed journals. Professor Miller and his colleagues at the University of California at San Diego wrote recently that plausible processes for the prebiotic formation of nucleotides or nucleosides have never been demonstrated (3).

Regarding the prebiotic formation of nucleic acids, Professor Robert Shapiro of New York University wrote: “Many steps would be required which need different conditions, and therefore different geological locations. The chemicals needed for one step may be ruinous to others. The yields are poor, with many undesired products constituting the bulk of the mixture. It would be necessary to invoke some imagined processes to concentrate the important substances and eliminate the contaminants. The total sequence would challenge our credibility, regardless of the time allotted for the process” (4). Professor Shapiro has consistently maintained this position in a series of articles in professional peer-reviewed journals (5). He wrote to me in a letter in May 2003 that there is no reason to believe that there were nucleotides in prebiotic times. He also wrote that popular presentations and biology textbooks on many levels, even up to university level, often make misleading statements that nucleotides in concentrations needed for evolution were easily available in prebiotic times. He called such statements “mythology” (6). Another chemistry professor who revealed this mythology is Professor Bruno Vollmert of the University of Karlsruhe in Germany (7).

Professor Leslie Orgel of the Salk Institute in San Diego, California, who has published more than two hundred articles on prebiotic chemistry in peer-reviewed professional journals, and Professor Gerald Joyce of the Scripps Research Institute in La Jolla, California, who has published dozens of articles on prebiotic chemistry in professional journals, are internationally renowned as leading experts in the field of prebiotic chemistry. They have worked for decades in this field. They wrote that the binding of purine nucleobases to ribose occurs “in relatively low yield,” and the binding of pyrimidine nucleobases to ribose “in reasonable yield” has not been achieved (8).

The prebiotic oligomerization (binding together) of nucleotides to produce oligonucleotides is opposed by water. A common scenario for prebiotic oligomerization is the drying out of a pond containing nucleotides. As water is removed from the pond by evaporation, the concentration of nucleotides increases to the point where oligonucleotides are formed. This is of course reasonable, but the problem is that oligonucleotides will be broken back down (hydrolyzed) to nucleotides when water is reintroduced. Water must be reintroduced to mediate the next step in evolution, which is the replication of the oligonucleotides by alignment of complementary nucleotides. Water is needed to bring in the individual nucleotides and align them next to the complementary nucleotides of the already-existing oligonucleotide (A with U and C with G).

In the 1960s Professor Orgel and coworkers at the Salk Institute performed numerous experiments on nucleotide oligomerization. They wrote that nucleotide oligomerization is catalyzed by the water-soluble condensing agent 1-ethyl-3-(3-(dimethyl-amino)-propyl)-carbodiimide, but this condensing agent was not available in prebiotic times (9). This is confirmed by consulting the process for synthesizing this condensing agent given in chemistry textbooks (10). Orgel and coworkers wrote: “We have attempted these same reactions using ´prebiotic´ condensing agents, but without success” (11). They noted: “Adenosine triphosphate forms a stable helix with polyuridylic acid but then undergoes hydrolysis without forming appreciable amounts of oligonucleotides” (12). This observation of the failure of nucleoside triphosphates to oligomerize in aqueous solution is still being cited thirty years later (13), and recent studies support it: in the presence of even small amounts of water, the rate of oligomerization of nucleoside 5´-triphosphates is much smaller than the spontaneous rate of hydrolysis of RNA (14).

In April 2003, I requested Professor Ronald Breaker of Yale University to refer me to technical papers giving the rate of formation of oligonucleotides from monoribonucleotides in aqueous (watery) solution as a function of the concentration of the monoribonucleotides, the concentration of various amines, and the concentration of various metal ions. He wrote back to me: “There is no simple answer for this question and, most likely, the data is not available. The rate of spontaneous coupling of monomers to form a dinucleotide will depend upon the form of the monomer. For example, a nucleoside monophosphate will never couple to another nucleoside monophosphate without activation. A triphosphate form is activated, but the rate of coupling should be far slower than that of spontaneous hydrolysis. In contrast, a monophosphate that has been activated by imidazole groups will be far faster but, again, much slower than if they are templated, as done by Orgel's group.” As discussed below, no one has published a prebioticly-plausible scenario for this activation, and templating has other fatal difficulties. (A template is an already-existing oligonucleotide).

Amines attached to the polyphosphates increase the rate of nucleotide oligomerization, but the process of attachment is inefficient in the presence of water (15).



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