History Nature of the Gene

The tremendous successes of the Morgan group often overshadow a simultaneous tradition of exploring the nature of gene action. The problem of how genes produce their effects was the domain of physiological genetics. As early as 1911, A. L. and A. C. Hagedoorn had proposed that genes acted as chemical catalysts. In 1916 Richard Goldschmidt interpreted genes as George W. Beadle, colleague of Edward Tatum. enzymes, while Sewall Wright explained coat-color patterns in terms of genetic regulation of enzymes in pigment-formation pathways. Many different geneticists sought to understand the action of genes in terms of their regulation of the rates of chemical reaction, the production of specific chemical products, and the induction of developmental processes. The incredible biochemical complexity of developmental and physiological processes, however, meant that physiological genetics made relatively slow progress.

The gap between genetics and biochemistry was narrowed in 1941, when George Beadle and Edward Tatum began to use the microorganism Neurospora to dissect biochemical processes. By growing Neurospora on media with different chemical compositions, Beadle and Tatum were able to devise a system for detecting specific changes in the biochemical abilities of their organism. Careful study of biochemical mutants led the two researchers to propose the "one gene-one enzyme" theory, linking genes to specific enzymes and the chemical reactions they catalyzed. Although this association was not new, Beadle and Tatum's work invigorated the field and encouraged the creation of biochemical genetics as a field of study.

Later it was discovered that many proteins are not enzymes, but instead may be signaling molecules or receptors, or may play structural roles. Thus "one gene-one enzyme" was modified to "one gene-one protein." It was also discovered that many functional proteins are composed of several distinct amino acid chains (polypeptides) whose corresponding DNA sequences were not necessarily close together or even on the same chromosome, leading to the "one gene-one polypeptide" formulation of the gene definition.

Like the study of gene action, the nature of the gene itself was understood as a biochemical problem early in the twentieth century. Because chromosomes were known to be composed of proteins and nucleic acids, many geneticists proposed specific molecular mechanisms to explain genetic changes or mutations. In 1919 Carl Correns had proposed that the gene was a large molecule with a number of side chains. Mutations were caused by changes in these side chains. Hermann Muller's pioneering work on the ability of X rays to induce mutations led Nikolay Timofeeff-Ressovsky, Karl Zimmer, and Max Delbrück to investigate the relationship between dose and mutability. The resulting model of mutation, published in 1935, provided a quantum mechanical mechanism for the molecular effects of the ionizing energy of X rays. As the nature and causes of mutation became a more prominent part of genetics, the importance of understanding the molecular basis of the gene also became widely recognized.