At a time when his colleagues were searching for genes in the nuclear genome, Douglas Wallace set himself apart by initiating a research program on mitochondrial genes. The mitochondrion is an organelle in the cytoplasm of all human cells that is known as the "powerhouse" of the cell since it is the primary source of the cell's energy. It contains a circular piece of DNA that is actually a second human genome. Although it is quite small and contains only genes that are specifically associated with the functions of the mitochondrion itself, this DNA has proven to be very important since mutations in the genes located there have been implicated in a variety of different human diseases. Wallace realized quite early that elucidation of the mitochondrial genome would be as critical to the complete understanding of the human body as were the studies on the nuclear genes.

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