The Proteinoid Theory of the Origin of Life And Competing Ideas SIDNEY W. FOX (Nucleic acid-coded) Contemporary cell ATP mechanisms Genetic code Model and theory Downloaded from http://online.ucpress.edu/abt/article-pdf/36/3/161/31762/4444705.pdf by guest on 24 September 2021 complete to this b point by 1967- Protocell (Ultrastructured, selectively permeable, H20 reproductive) THE NUMBER OF REQUESTS I am receiving for photo- Protoprotein (Enzymic, micrographs suggests that we can expect dozens of ordered) new textbooks with passages or chapters on the -H20 origin of life. Dozens of textbooks of biology with a Amino acids such inclusions have indeed already appeared, most of them since 1971. The first textbook of biochemistry to include a chapter on the origin of life was Albert I -H20 Lehninger's, published in 1970. Lehninger has ex- (Amino acid precursors) plained there that armchair speculation was being replaced in the 1960s by serious scientific investiga- I tion. Primordial organic matter (galactic organics, etc.) Late in the 1960s, in fact, we had one relatively Fig. 1. From organic matter to a reproductive protocell and complete theory (and physical model) of the origin beyond. Numerous experimental alternatives are available of a reproducing protocell, derived from geologically up to stage a but not above. Between a and b the steps are compatible sequentially, and the conditions are geologically relevant experiments. During the development of relevant. this theory, alternatives for individual component concepts have appeared. I have recently presented The extensive evidence (Kenyon 1973) for the elsewhere (Fox 1973a) a comparison of some of the proteinoid origin of life has been reviewed elsewhere alternative concepts. In responding to the present (Fox and Dose 1972). The essential features of the invitation, I shall again outline the proteinoid theory theory, derived from the physical model, are seen in and then examine competing or alternative concepts fig. 1. Mixtures of a-amino acids are copolymerized in the light of our sequential experimental model. by heat. The resultant proteinoids contain ordered My view of most of the competing concepts is sequences of amino acids and arrays of enzymelike expressed precisely by Florkin and Stotz (1972): activity. Upon contact with water, the proteinoids Accordingto [John] Northrop,there is a common patternin all ... Sidney W. Fox is professor of chemistry and --- ... controversies "Thereis a compli- director of the Institute for Molecular and cated hypothesis, which usually entails an elemnent .... of mysteryand severalunnecessary assumptions. This Cellular Evolution at the University of a is opposedby a more simple explanation,which con- Miami, Coral Gables, Fla. 33134. His Ph.D. tains no unnecessaryassumptions. The complicated is in biology (biochemistry) from the Cali- fornia Institute of Technology. He has been one is always the popularone at first, but the simpler . one, as a rule, eventuallyis found to be correct.This U.S.-U.S.S.R. interacademy exchange lec- j processfrequently requires 10 to 20 years.The reason turer with A. I. Oparin (1969), and he is for this long time lag was explainedby Max Planck. vice-president of the International Society He remarked that 'scientists never change their for the Study of the Origin of Life. He has received the minds,but eventually die."' Florida Academy of Sciences gold medal, the Priestman lectureship, the Iddles award, and a number of other honors specifically for his advances in the theory of the origin of In the case of the proteinoid theory, as in those life, in addition to recognition for his contributions to bio- cases described by Northrop, we have a relatively chemistry, especially amino acid sequence determination. He simple explanation, with no unnecessary assump- was recently presented with a festschrift; the authors in- tions. The clude Pauling, Szent-Gyorgyi, Calvin, Lipmann, Charles explanation emerged from experiments so Price, and Florkin. Fox is the author or coauthor of more simple that innumerable students at all levels have than 200 technical articles and several books. The present repeated many of them. paper was given at the 1973 NABT convention. 161 Fig. 2 is a view of proteinoid. Proteinoid is what is produced in the laboratory; protoprotein is the term for proteinoid that, according to interpretation, originated spontaneously on the Earth. The theory has emerged from the preparation and properties of proteinoid. These polymers have molecular weights, typically, of 5,000-12,000; they contain some propor- tion of each of the amino acids common to contem- porary protein; and qualitatively they have virtually all of the properties of contemporary protein (Fox and Dose 1972). The polymers are usually produced in substantial yield, such as 20-60%, from amino acids. The most striking feature of the process is its utter simplicity-a simplicity imputable to condi- tions at the surface of the Earth even now. According to our analyses, the principal reasons that our laboratory is the only one to have presented 41,~~~~~~~~~~ a comprehensive physical and conceptual model (in Downloaded from http://online.ucpress.edu/abt/article-pdf/36/3/161/31762/4444705.pdf by guest on 24 September 2021 1967) for the origin of life are the following: 1. Life began in essentially only one way, al- though it may have done so innumerable times. 2. We have studied processes in open systems, comparable to what has occurred in the geologic realm. Closed flasks used in the laboratory by others are far less relevant to the geologic realm. 3. We have discovered for each stage self-ordering phenomena leading to the next stage. 4. The proteinoid microsphere is found to have numerous properties of the contemporary cell and to be evolvable toward the latter. Such emergent functions had to be determined by experiment; they were not predicted. Some of the experiments, however, began as work- ing hypotheses. The organized body of interpretations is referred to as the proteinoid theory of the origin of life (Florida Academy of Sciences 1968); it is a sequentially coherent conceptualization. One of the earliest of the competing concepts is that of the famous chemist Emil Fischer (1906), who said (approximate translation): If today, througha lucky accident,with the help of a brutal reaction,for example, a melting of amino Fig. 2. Left:indiscriminately heated a -amino acids. Right: acids in the presence of a water-removingmedium, a mixture of a-ammno acids containing aspartic acid and there shouldsuccessfully be produceda true protein, glutamic acid, following purification by dialysis-the material and if it were furtherpossible, which is still unlikely, is called proteinoid. to identify the artificial product with the natural material-this would benefit protein chemistry little yield huge numbers of model cells. These lack some and biology not at all. of the properties of contemporary cells, but they possess others. The properties observed include a What was indeed true in 1906 is not true today; content of highly ordered, protometabolically active there is enough additional understanding to produce molecules, ultrastructure, some kinds of selective true significance. Also, if Fischer had recognized the permeability, and the ability to reproduce by four ease with which material resulting from melted physical mechanisms. The properties found are those amino acids would easily form a kind of cell, he essential for further evolution. Up to the stage of might have seen a relationship to what is the first amino acids, many alternative explanations are avail- problem of biology: the origin of life. But his view able (Fox and Dose 1972; Fox et al. 1973). The sub- must have been in part the understandable myopia sequent two steps are without experimentally de- of one early chemist. Charles Darwin, however, veloped alternatives. Those above the upper hori- imagined in a letter to a friend in 1871 "that a pro- zontal line in fig. 1 are based on partial experimental tein compound was chemically formed ready to demonstration (Fox 1974). undergo still more complex changes" (F. Darwin 162 THEAMERICAN BIOLOGY TEACHER, MARCH 1974 1896). Fischer's view and Darwin's earlier view seem Table 1. Principal advances in concept resulting from in- to me to have been truly competitive with each other. vestigation up to an act of spontaneous generation, with However that situation is analyzed, I found, as late inhibitory assumptions. as 1963, a number of chemists and biochemists whose Advance Inhibitory assumption views were much like those of Fischer in 1906; in some cases it seemed to me that I was confronting an 1. Protein(oid) can be pro- Synthesis of protein re- duced acellularly quires a cell emotional as well as a dialectic barrier. The principal advances in the art up to an act of 2. a-Amino acids can be a-Amino acids are decom- spontaneous generation of a (minimal) cell are seen thermally copolymerized posed by heating (Carothers and in table 1. Also included are competing assumptions nylon) that were prevalent at the time the experiments were 3. Heated a-amino acids Disordered polymers would designed. Had these negative assumptions and others order themselves result (E. Fischer, A. I. Oparin, etc.). Nucleic acids been taken seriously, the experiments would not were needed have been performed. The idea that synthesis of protein requires a cell 4. Arrays of enzymic ac- Matter cannot organize it- 3 self is simply one of the later battles with vitalism, this tivity result from contest having often to be refought. The experimental 5. Proteinoids aggregate to advance number 1 is one modern equivalent of form minimal cells upon Downloaded from http://online.ucpress.edu/abt/article-pdf/36/3/161/31762/4444705.pdf by guest on 24 September 2021 contact with water Wohler's synthesis of urea in the absence of a cell. Ml 2 0 B1 B1 e 3 4 a t-2 ,B1 B2 U t , o~~~~~~~~~~~~~~ Fig.