Science Discovers God

Science Discovers God

The failure of demonstrating the prebiotic formation of a molecular system

Science Discovers God

An expose of the sustained failure of the world’s best chemists to demonstrate

the prebiotic formation of a molecular system capable of evolving into the

sophisticated nucleic acids of modern cells

14 June 2003

Madhavendra Puri das

Introduction

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 fusion 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 (Hollis J. et al Astrophysical Journal, 2000, 540, L107-L110; Irvine W. Space Science Review, 1999, 90, 203-218; Page 242 of Cronin J, Chang S. “Organic matter in meteorites: molecular and isotopic analysis of the Murchison meteorite.” In The Chemistry of Life’s Origins, editor J. Greenberg, Kluwer Publishers, 1993). Another guide to the kinds of organic molecules existing when the earth formed are carbonaceous chondrites, which have been found to contain various organic molecules, including amino acids, hydroxy acids, monocarboxylic acids, dicarboxylic acids, amines, amides, aliphatic hydrocarbons, aromatic hydrocarbons, aldehydes, ketones and nitrogen heterocycles (Sephton M. Nature Product Report, 2002, 19, 292-311; Cooper G, et al. Nature, 2001, 414, 879-882; Cronin J, Chang S. “Organic matter in meteorites: molecular and isotopic analysis of the Murchison meteorite.” In The Chemistry of Life’s Origins, editor J. Greenberg, Kluwer Publishers, 1993, pages 209-258; Cronin J. et al. in Meteorites and the early solar system, editor J. Kerridge, University of Arizona Press, 1988, pages 819-857). None of these simple primordial molecules (or any combination of them) has been shown to be capable of evolving into the sophisticated nucleic acids of even the simplest bacterium.

What is meant by “capable of evolving”? Self-replication without mutations does not allow evolution, since all the copies are the same as the original. Self-replication with mutations generates variation, which leads to differential survival rates due to natural selection. This means that evolution could not start until simple primordial molecules achieved the power of self-replication with mutations. Not only that, but these molecules must have been able to evolve into sophisticated nucleic acids. No such molecules have been discovered despite intense search for them during the last fifty years at the best universities in the world. This will be shown in detail below. Nucleic acids are most rationally viewed as the products of design. A specific design hypothesis will be described.

I apologize for the technical nature of this discussion, but it is unavoidable. A video with helpful diagrams will soon be available on my website (http://my.tele2.ee/svs/).

The RNA Dream World

RNA is a chain of beta-D-ribo-furanosyl-nucleotides, each of which is composed of phosphate, the sugar ribose, and one of four nucleobases: adenine, guanine, cytosine and uracil. The first two nucleobases are called purine nucleobases, and the second two are called pyrimidine nucleobases. DNA is the same except that the sugar deoxyribose replaces ribose. Since both of these sugars possess five carbon atoms, they are called pentoses. The only difference between them is that ribose possesses a hydroxyl group attached to the 2’ carbon atom, whereas deoxyribose does not. We use the term “nucleic acid” only for RNA and DNA; if some sugar other than deoxyribose or ribose is present, or if other nucleobases are present, we will call it a “nucleic acid analog” (Page 69 of Joyce G, Orgel L. in The RNA World, Second Edition, 1999, editor R. Gesteland, New York: Cold Spring Harbor Lab).

Since there are reports describing a potentially prebiotic (four billion years old or older) synthesis of ribose (see below), our discussion of nucleic acids will focus on RNA. The pyranosyl form of ribose has all five carbon atoms in the pyranose ring, whereas the furanosyl form of ribose has the 5’ carbon atom cis to the furanose ring. When we say RNA we mean ribose in its furanosyl form. The pyranosyl form of RNA is called p-RNA. Beta means that the nucleobase is cis to the furanose ring. L-ribose means that the hydroxyls at the 2’ and 3’ carbon atoms are cis to the furanose ring, whereas these hydroxyls are trans to the furanose ring in D-ribose. When we use the term “nucleotide” without any other qualifying adjectives, it is understood to mean a beta-D-ribo-furanosyl- nucleotide. A nucleotide without phosphate is called a nucleoside.

Non-chemists, especially biologists, often “dream” (Page 50 of Joyce G, Orgel L. in The RNA World, Second Edition, 1999, editor R. Gesteland, New York: Cold Spring Harbor Lab) that four billion years ago there were pools containing a high enough concentration of nucleotides to start evolution and keep it running. This dream is shattered by chemistry professors at the best universities in the world who have spent decades studying the formation of nucleic acids under the conditions existing four billion years ago. Professor Stanley Miller achieved world-wide fame in 1953 by being the first to perform the spark-discharge experiment for the abiotic production of amino acids and other organic compounds; he has been working steadily in this field for fifty years. Professor Miller and his colleagues at the University of California at San Diego wrote that plausible processes for the formation of nucleotides or nucleosides four billion years ago have never been demonstrated (Page 3868 of Nelson K, Levy M, Miller S. Proceedings of the National Academy of Sciences USA, 2000, 97, 3868–3871).

Regarding the formation of nucleic acids four billion years ago, 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” (Page 186 of Shapiro R. Origins: a Skeptic’s Guide to the Creation of Life on Earth, 1986, New York: Summit Books). Professor Shapiro has consistently maintained this position in a series of publications in scientific journals (Shapiro R. Origins of Life and Evolution of the Biosphere, 1995, 25, 83-95; Shapiro R. Proceedings of the National Academy of Sciences USA, 1999, 96, 4396-4401; Shapiro R. IUBMB Life, 2000, 49, 173-176; Shapiro R. Origins of Life and Evolution of the Biosphere, 2002, 32, 275-278).

He wrote to me in a letter in May 2003 that there is no reason to believe that there were nucleotides four billion years ago. 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 four billion years ago. He called such statements “mythology”. (Shapiro R. Origins: a Skeptic’s Guide to the Creation of Life on Earth, 1986, New York: Summit Books). Another chemistry professor who revealed this mythology is Professor Bruno Vollmert of the University of Karlsruhe in Germany (Das Molekül und das Leben, 1985, Hamburg: Rowohlt).

Professor Leslie Orgel of the Salk Institute and Professor Gerald Joyce of the Scripps Institute are internationally renowned as leading experts in this field. 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 (Page 68 of Joyce G, Orgel L. in The RNA World, Second Edition, 1999, editor R. Gesteland, New York: Cold Spring Harbor Lab).

The oligomerization (binding together) of nucleotides to produce nucleic acids in the presence of water is a problem. In the 1960s Professor Orgel and coworkers at the Salk Institute performed numerous experiments on this. They wrote that nucleotide oligomerization is catalyzed by the water-soluble condensing agent 1-ethyl-3-(3-dimethyl- amino)-propyl)-carbodiimide hydrochloride, but this condensing agent was not available in prebiotic times (Weimann B, Lohrmann R, Orgel L, Schneider-Bernloehr H, Sulston J. Science, 1968, 161, 387). This is confirmed by consulting the process for synthesizing this condensing agent given in chemistry textbooks, such as page 972 of Professor Jerald March, Advanced Organic Chemistry, 4th edition, 1992, New York: John Wiley. Orgel and coworkers wrote: “We have attempted these same reactions using ´prebiotic´ condensing agents, but without success” (Weimann B, Lohrmann R, Orgel L, Schneider-Bernloehr H, Sulston J. Science, 1968, 161, 387). They noted: “Adenosine triphosphate forms a stable helix with polyuridylic acid but then undergoes hydrolysis without forming appreciable amounts of oligonucleotides” (Weimann B, Lohrmann R, Orgel L, Schneider-Bernloehr H, Sulston J. Science, 1968, 161, 387). This observation of the failure of nucleoside triphosphates to oligomerize in aqueous solution is still being cited thirty years later (Page 4330 of Prabahar K, Ferris J. Journal of the American Chemical Society, 1997, 119, 4330-4337), 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 (Professor Bruno Vollmert, University of Karlsruhe, Germany, Das Molekül und das Leben, 1985, Hamburg: Rowohlt; Professor Robert Shapiro, New York University, Personal Communication, April 2003; Professor Ronald Breaker, Yale University, Personal Communication, April 2003; Professor Gerald Joyce, May 2003, Personal Communication). Amines attached to the polyphosphates increase the rate of nucleotide oligomerization, but this attachment only occurs in the absence of water (Lohrmann R. Journal of Molecular Evolution, 1977, 10, 137-154) or in the presence of condensing agents that were not available four billion years ago. For example, a published procedure for attaching the compound 1-methyladenine to a nucleotide involves the condensing agent 1-ethyl-3-(3-(dimethylamino)-propyl)-carbodi- imide hydrochloride which, as discussed above, was not available in prebiotic times. The published procedure is as follows: “A mixture of 5’-NMP-H2O (free acid) (0.33 mmol) and 1-methyladenine (0.049, 0.33 mmol) was dissolved in water (2 mL), and the pH of the solution was adjusted to 5. 1-Ethyl-3-(3-(dimethylamino)-propyl)-carbodiimide hydro- chloride (EDAC) (0.191 g, 1 mmol) was added to this reaction mixture with stirring. Two additional portions of EDAC (2 x 0.0636 g, 2 x 0.33 mmol) were added at 1 h intervals, and the reaction was allowed to proceed for 4 h. During the reaction, the EDAC was hydrolyzed to the corresponding urea which was separated from the activated nucleotide by passing the reaction mixture through a DOWEX 50 W-X8 cation exchange column and elution with water (150 mL)” (Page 4331 of Prabahar K, Ferris J. Journal of the American Chemical Society, 1997, 119, 4330-4337).