One gene-one enzyme hypothesis.

In the early part of the twentieth century, genetics was becoming an established discipline, but the relationship between genes and how they are expressed as phenotypes was not yet understood. Biochemistry was also in its infancy, particularly the study of the enzyme-catalyzed chemical reactions of metabolic pathways. In 1902, a British medical doctor named Archibald Garrod brought genetics and biochemistry together in the discovery that a human disease called alkaptonuria, which causes individuals with the disease to accumulate a black pigment in their urine—was inherited as a recessive trait. Equally important, however, was Garrod’s observation that alkaptonurics were unable to metabolize alkapton, the molecule responsible for the black pigmentation, an intermediate in the degradation of amino acids. Garrod’s conclusion was that people with alkaptonuria lack the enzyme that normally degrades alkapton. Because it thus appeared that a defective gene led to an enzyme deficiency, Garrod predicted that genes form enzymes. This statement was the precursor of what came to be known as the one gene-one enzyme hypothesis.