In 1902, a British physician, Archibald Garrod, was working with one of the Mendelian geneticists, when he noted that certain diseases he encountered among his patients seemed to be more prevalent in particular families. By examining several generations of these families, he found that some of the diseases behaved as if they were the product of simple recessive alleles. Garrod concluded that these disorders were Mendelian traits and that they had resulted from changes in the heredity information in an ancestor of the affected families.
Garrod investigated this ordeal in greater detail. In alkaptonuria the patients produced urine that contained mogentisic acid (alkapton). This substance oxidized rapidly when exposed to air, turning the urine black. In normal individuals, homogentisic acid is broken down into simpler substances. Garrod concluded that patients suffering from alkaptonuria lacked the enzyme necessary to catalyze this breakdown. He speculated that many other inherited diseases might also reflect enzyme deficiencies.