Sir

Hubert P. Yockey in Correspondence (Nature 415, 833; 2002) claims that Stanley L. Miller's classical synthesis of amino acids and other organic compounds with electric discharges using possible prebiotic conditions (Science 117, 528; 1953) was a mere repetition of several previous electrochemical syntheses performed by Walther Löb and others in the early twentieth century. This is not a fair assessment of the significance of Miller's experiment.

Although some of Löb's results may have some bearing on our understanding of prebiotic syntheses, part of the significance of Miller's experiment lies not only in the production of amino acids and other compounds, but in their synthesis under what was viewed at the time as plausible primitive Earth conditions. Few, if any, scientific ideas are the product of spontaneous thoughts — most theories, experiments and interpretations have been preceded by many others, and the same is true of Miller's experiment. Even if one disagrees with the assumptions underlying the simulation by Miller and Harold Urey of the primitive Earth, it deserves recognition not only because of its intrinsic merits, but also because it opened new avenues of empirical research into the origin of life.

Löb did indeed report the synthesis of glycine by exposing wet formamide to a silent discharge (Ber. Dtsch Chem. Ges. 46, 684; 1913). He suggested that because of either the ultraviolet light or the electrical field generated by the silent discharge, formamide is first converted to oxamic acid, which in turn is reduced to glycine. He also claimed that glycine is produced when wet carbon monoxide and ammonia are subjected to the silent discharge; he proposed formamide as the intermediate in this synthesis. Löb theorized that glycine might also be produced from wet carbon dioxide and ammonia in a pathway wherein formamide was again the intermediate, but he did not demonstrate this directly.

Although Löb apparently did produce glycine from formamide, this cannot be considered a prebiotic reaction because formamide would not have been present on the primitive Earth in any significant concentrations. It is also possible that the wet carbon monoxide and ammonia led to HCN synthesis, which would have produced glycine on polymerization and hydrolysis.

From a careful reading of Löb's 1913 paper (in early twentieth-century German!) it is clear that his motivation for doing the experiment was to try to understand the assimilation of carbon dioxide and nitrogen in plants. There is no indication that he had any interest in the question of how life began on Earth, or in the synthesis of organic compounds under possible prebiotic conditions. Neither Aleksander Oparin, J. B. S. Haldane nor Urey made any mention of Löb's work, which given Oparin's extensive review of early relevant literature suggests it was considered unimportant. To the best of our knowledge, Löb's work was first discussed within the context of prebiotic chemistry by Miller (J. Am. Chem. Soc. 77, 2351; 1955).