Thermal proteins are synthetic polypeptides, previously referred to as 'proteinoids,' made by heating certain mixtures of amino acids. In proteins, amino acids are linked by peptide bonds which form as a result of the loss of water. Following the much-publicized success of the Milller-Urey experiment (1953), it was hoped that by heating amino acids to a sufficiently high temperature, to drive off water, the next great step in retracing the chemical evolution of life-the synthesis of proteins-might be achieved in the laboratory. However, early work in this direction was discouraging and resulted only in the production of tarry materials. A breakthrough came in 1956 following the observation by Sydney Fox and his colleagues that of the 20 amino acids found in proteins, two, aspartic acid and glutamic acid, were especially prevalent, accounting for between a quarter and a half of the amino acid content of protein molecules in general. It was also known that aspartic and glutamic acids play key roles in certain biological processes. Therefore, in their experiments in prebiological synthesis, Fox and his group tried heating a mixture of amino acids in which aspartic and glutamic acids were present in excess. After three hours of heating at about 180°C, they obtained an amber-colored liquid in which they discovered a complex polymer with a structure like that of a protein. Further experiments revealed that these "proteinoids," which later became known as thermal proteins, had molecular weights from 3,000 to 10,000 and always contained some of each of the amino acids present in the starting mixtures.1 Moreover, against all expectations, the particular arrangements of amino acids making up thermal proteins turned out not to be random, but orderly and reproducible: the same mixture of amino acids would always combine in the same way.
Fox pointed out that the reactions in heated amino acid mixtures were not confined to the solid phase because, at the temperatures used, glutamic acid becomes a liquid. Also, the inclusion of phosphoric acid, which facilitated some of the reactions, served to provide a liquid environment. Fox quoted features of the proteinoid thermal synthesis reactions which were only discovered afterward in the biochemical mechanisms of living organisms. Most interesting of all were the later studies, conducted by Fox, Harada, and Kendrick which resulted in the production of rudimentary, cell-like structures known as microspheres.2
Until 1979, it was thought that the thermal proteins produced by heating amino acids were entirely synthetic and without counterparts in the biological world. Then the German biochemist Klaus Dose and his associates succeeded in showing that one of the products of Fox's experiments was flavin, a naturally-occurring protein. Indeed, flavins play a significant role in the energy metabolism of cells, and riboflavin, in particular, is a standard component of the human diet.
1. Fox, S. W. "Evolution of Protein Molecules and Thermal Synthesis of
Biochemical Substances." American Scientist, 44, 347 (1956).
2. Fox, S. W., Harada, K., and Kendrick, J. "Production of Spherules fro, Synthetic Proteinoid and Hot Water." Science, 129, 1221 (1959).