The British biochemist and physician Archibald Garrod had mentioned in his book named "Inborn errors of metabolism" that there are inherited genetic disorders such as phenylketonuria and alkaptonuria which are caused by the absence of particular enzymes.

Beadle and Tatum working with the mutants of the fungus Neurospora showed that the absence of a gene in a mutant leads to absence of an enzyme in a metabolic pathway (chain of biochemical reactions) midway. Thus was proposed that one gene was responsible for the production of one enzyme and this was called the one gene one enzyme hypothesis.

Later, it was found that an enzyme (a protein) may be made of more than one polypeptide and one gene controlled production of one polypeptide (chain of amino acids in a protein).