Sidney W. Fox

Thermal polymerization of amino acids and a theory of biochemical origins

Bei Überschuss von Glutaminsäure und Asparaginsäure werden zahlreiche Aminosäuren thermisch kopolymerisiert. Das Studium der Reaktionen und Nebenreaktionen führt zu einer Theorie über den thermischen Ursprung biochemischer Systeme.

Thermal synthesis of amino acids and the origin of life

The recent review by Marshall (1994) of the production of amino acids from the interstellar components, formaldehyde and ammonia, is placed in the larger context of the origin of life. Thermal energy, being ubiquitous in the Earth, emerges as the sole necessary form of energy. To appreciate the overview of the natural evolutionary sequence it is necessary to recognize stepwiseness in evolution, a principle that has however been often ignored. Since self organization of thermal protein to cells is instantaneous, but only one step in a geochemical ladder, individual steps may be regarded as instantaneous, while the sequence requires measurable time. Two steps indicated are extrusion of a hot, dry organic magma of amino acids --> peptides into an aqueous environment in which occurs a second step of self organization. In this paper, spinoffs of the defensible theory for the origin of life have been briefly reviewed as a fundamental consequence of nonrandom thermal copolymerization of amino acids.

Experimental retracement of the origins of a protocell

Although Oparin used coacervate droplets from two or more types of polymer to model the first cell, he hypothesized homacervation from protein, consistent with Pasteur and Darwin. Herrera made two amino acids and numerous cell-like structures (“sulfobes”) in the laboratory, which probably arose from intermediate polymers. Our experiments have conformed with a homoacervation of thermal proteinoid, in which amino acid sequences are determined by the reacting amino acids themselves. All proteinoids that have been tested assemble themselves alone in water to protocells. The protocells have characteristics of life defined by Websters Dictionary: metabolism, growth, reproduction and response to stimuli in the environment. The protocells are able also to evolve to more modern cells including the initiation of a nucleic acid coding system.Principal spinoffs from the results are revised evolutionary theory, models for protoneurons and networks thereof, and numerous industrial applications of thermal polyamino acids. Life itself has thus been reaffirmed to be rooted in protein, not in DNA nor RNA, which are however crucial to inheritance in modern life as “instruction manual” (Kornberg).Recognition of the advances have been considerably delayed by the deeply held assumption that life began by chance from random polymerization of amino acids, in contrast to the experimental findings. The concepts of DNA/RNA-first and protein-first are reconciled by a rise-and-fall progression as often seen in biochemical and biological evolution.The fact that amino acids order themselves explains in turn that thermal copolyamino acids are finding numerous applications. The entire sequence of processes in the proteinoid origins theory is now seen to be highly deterministic, in close accord with Einstein.

Self-organization of the protocell was a forward process

Yockeys (1981) interpretation of information theory relative to concepts of self-organization in the origin of life is criticized on the ground that it assumes that each amino acid residue type in a given sequence is an unaided information carrier throughout evolution. It is argued that more than one amino acid residue can act as a unit information carrier, and that this was the case in prebiotic protein evolution. Forward-extrapolation should be used to study prebiotic evolution, not backward-extrapolation. Transposing the near-random internal order of modern proteins to primitive proteins, as Yockey has done, is an unsupported assumption and disagrees with the results of experimental models of the primordial type. Studies indicate that early primary information carriers in evolution were mixtures of free alpha amino acids which necessarily had the capability of sequencing themselves.

Experimental Retracement of Terrestrial Origin of an Excitable Cell: Was it Predictable?

A largely historical treatment of how the evolutionary sequence to the first synthesis of life under terrestrial conditions, as retraced in the laboratory, is presented. The insights of such pioneers as Pasteur on self-organization of matter to “beings” are related. The recent acknowledgment of fruitless attempts by experts in DNA-first. RNA-first. and in irrelevance of the concept of random beginnings are cited. Updating of origins from amino acid-instructed genetically primary thermal protein is detailed. The essence of the finding of internal nonrandomness is emphasized, as well as the critical nature of studying the initial steps of molecular evolution in a synthetic direction. The total flowsheet for amino acid precursors ➔ protocell = protoneuron is updated. The results of experiments are tested against the characteristics of life as it is usually defined: metabolism, growth, reproduction, and response to stimuli such as light.

Thermal Peptides as the Initial Genetic System

The Thermal Protein-First Paradigm describes activities of protocells and metaprotocells within the Domain Protolife. The biological information that enabled protolife activities was derived by thermal proteins through self-ordering of amino acids during the polymer syntheses: generally by melting amino acids (including aspartic acid, glutamic acid, or both) in a copolymerization reaction. The transfer of information in this activity resulted in the first genetic system when thermal proteins in contact with water self-organized to form protocells, the smallest units of protolife. Polypeptide and polynucleotide syntheses have been demonstrated to occur within photophosphorylating protocells. We infer: coevolution of these products within protocells ultimately yielded informed DNA; and, DNA storage, transfer, and gene expression mechanisms (i.e., Central Dogma for contemporary molecular biology) evolved from DNA that had little biological information. The protocells exhibited traits of the last common ancestor(s) of prokaryotic cells. Without mRNAs to regenerate them in ribosomal protein synthesis, thermal proteins were replaced as information molecules, enzymes, and structural units.

The Origin of Mind and Life

Successful retracement in the laboratory under terrestrial conditions of synthesis of the first cell from progenitor thermal protein has been recorded (Fox et al., 1995; Enger and Ross, 1997). This retracement has benefited from recognition of some reversibility in molecular evolution (Atkinson and Fox, 1951; Fox et al., 1995a; Fox et al., 1995b). A number of other new advances were also required. Sequence analysis of amino acid residues was a method needed early (Fox, 1945). (While the 1945 prospectus preceded analysis of insulin and other related developments by other workers), the evolutionary applications led to recognition of self-sequencing of amino acids into polymers when heated, self-assembly of the resultant thermal proteins to first living cells (Fox, 1971; Fox et al., 1995; Enger and Ross, 1997) and a number of other advances.

Animate Protocells from Inanimate Thermal Proteins

Seven thermal protein complexes and the dialyzed products from one of these produced typical protocells (0.1–10 µm in diameter) on their surfaces when moistened with water. Protocells (about 0.5 µm in diameter) were visualized (800–1200x): almost instantly at 60 C; within a few min at 23 C; and, after about 15 min at 4 C. Protocells of about 3.0 µm diameter were observed associated with the thermal protein surfaces: within 30 sec to a few min at 60 C; after 4–10 min at 23 C; and, after 9 hr at 4 C. In all cases, the small protocells were free or in loose aggregates. The large protocells were often: free; linked in chains (filaments) or dendritic structures (5–15 protocells in the branched structures); or, more rarely, multi-linked protocellular clusters (15 or more protocells). This method of observing protocell formation provides opportunities for the study of factors involved in the self-assembly process and in protocell survival (e. g., effects of nutritional requirements for growth, differentiation, and reproduction).

Visually Retracing the Emergence of the Evolvable Protocell

Seven thermal proteins and two of their dialyzed products were observed (oil-immersion light microscopy l, 000x @ 60° C) as they were moistened with 1.0% aqueous solutions of each of seven salts to yield protocells by self-assembly. The spherical protocells ranged in diameters from 0.1 to 10 µm, but formed two populations most commonly ∼ 0.5 and ∼ 3.0 µm. The small protocellular population was first visible within 30 sec and the larger protocells formed about 30 sec to 4 min. later. Both populations increased slightly in diameter within the following 15–30 min.