Genes act by controlling cellular chemistry. Early in the twentieth century, Archibald Garrod, an English physician, made the first observation supporting this insight. Garrod noted that several recessive human diseases show defects in what is called metabolism, the general set of chemical reactions taking place in an organism. This observation led to the notion that such genetic diseases are “inborn errors of metabolism.”
Alkaptonuria
Garrod worked on a disease called alkaptonuria (AKU), or black urine disease. He discovered that the substance responsible for black urine was homogentisic acid, which is present in high amounts and secreted into the urine in AKU patients. He knew that, in unaffected people, homogentisic acid is converted into maleylacetoacetic acid; so he proposed that, in AKU, there is a defect in this conversion. Consequently, homogentisic acid builds up and is excreted. Garrod’s observations raised the possibility that the cell’s chemical pathways were under the control of a large set of interacting genes.
| Alkaptonuria is an inherited condition that causes urine to turn black when exposed to air. Ochronosis, a buildup of dark pigment in connective tissues such as cartilage and skin, is also characteristic of the disorder. This blue-black pigmentation usually appears after age 30. People with alkaptonuria typically develop arthritis, particularly in the spine and large joints, beginning in early adulthood. Other features of this condition can include heart problems, kidney stones, and prostate stones. |
However, the direct demonstration of this control was provided by the later work of Beadle and Tatum on the fungus Neurospora.