<P> The one gene--one enzyme hypothesis is the idea that genes act through the production of enzymes, with each gene responsible for producing a single enzyme that in turn affects a single step in a metabolic pathway . The concept was proposed by George Beadle and Edward Tatum in an influential 1941 paper on genetic mutations in the mold Neurospora crassa, and subsequently was dubbed the "one gene--one enzyme hypothesis" by their collaborator Norman Horowitz . In 2004 Norman Horowitz reminisced that "these experiments founded the science of what Beadle and Tatum called' biochemical genetics .' In actuality they proved to be the opening gun in what became molecular genetics and all the developments that have followed from that ." The development of the one gene--one enzyme hypothesis is often considered the first significant result in what came to be called molecular biology . Although it has been extremely influential, the hypothesis was recognized soon after its proposal to be an oversimplification . Even the subsequent reformulation of the "one gene--one polypeptide" hypothesis is now considered too simple to describe the relationship between genes and proteins . </P> <P> Although some instances of errors in metabolism following Mendelian inheritance patterns were known earlier, beginning with the 1902 identification by Archibald Garrod of alkaptonuria as a Mendelian recessive trait, for the most part genetics could not be applied to metabolism through the late 1930s . Another of the exceptions was the work of Boris Ephrussi and George Beadle, two geneticists working on the eye color pigments of Drosophila melanogaster fruit flies in the Caltech laboratory of Thomas Hunt Morgan . In the mid-1930s they found that genes affecting eye color appeared to be serially dependent, and that the normal red eyes of Drosophila were the result of pigments that went through a series of transformations; different eye color gene mutations disrupted the transformations at a different points in the series . Thus, Beadle reasoned that each gene was responsible for an enzyme acting in the metabolic pathway of pigment synthesis . However, because it was a relatively superficial pathway rather than one shared widely by diverse organisms, little was known about the biochemical details of fruit fly eye pigment metabolism . Studying that pathway in more detail required isolating pigments from the eyes of flies, an extremely tedious process . </P> <P> After moving to Stanford University in 1937, Beadle began working with biochemist Edward Tatum to isolate the fly eye pigments . After some success with this approach--they identified one of the intermediate pigments shortly after another researcher, Adolf Butenandt, beat them to the discovery--Beadle and Tatum switched their focus to an organism that made genetic studies of biochemical traits much easier: the bread mold Neurospora crassa, which had recently been subjected to genetic research by one of Thomas Hunt Morgan's researchers, Carl C. Lingegren . Neurospora had several advantages: it required a simple growth medium, it grew quickly, and because of the production of ascospores during reproduction it was easy to isolate genetic mutants for analysis . They produced mutations by exposing the fungus to X-rays, and then identified strains that had metabolic defects by varying the growth medium . This work of Beadle and Tatum led almost at once to an important generalization . This was that most mutants unable to grow on minimal medium but able to grow on "complete" medium each require addition of only one particular supplement for growth on minimal medium . If the synthesis of a particular nutrient (such as an amino acid or vitamin) was disrupted by mutation, that mutant strain could be grown by adding the necessary nutrient to the medium . This finding suggested that most mutations affected only a single metabolic pathway . Further evidence obtained soon after the initial findings tended to show that generally only a single step in the pathway is blocked . Following their first report of three such auxotroph mutants in 1941, Beadle and Tatum used this method to create series of related mutants and determined the order in which amino acids and some other metabolites were synthesized in several metabolic pathways . The obvious inference from these experiments was that each gene mutation affects the activity of a single enzyme . This led directly to the one gene--one enzyme hypothesis, which, with certain qualifications and refinements, has remained essentially valid to the present day . As recalled by Horowitz et al., the work of Beadle and Tatum also demonstrated that genes have an essential role in biosyntheses . At the time of the experiments (1941), non-geneticists still generally believed that genes governed only trivial biological traits, such as eye color, and bristle arrangement in fruit flies, while basic biochemistry was determined in the cytoplasm by unknown processes . Also, many respected geneticists thought that gene action was far too complicated to be resolved by any simple experiment . Thus Beadle and Tatum brought about a fundamental revolution in our understanding of genetics . </P>

Beadle and tatum's work was important in that it demonstrated that