2017 Benjamin Franklin Medal in Life Science presented to Douglas C. Wallace, Ph.D.

摘要

Mitochondria are tiny energy producing structures within all living cells and contain their own DNA. They were bacteria, similar to Rikettsia, which two to three billion years ago invaded an organism with a nucleus, and formed a symbiosis. There are hundreds to thousands within almost every human cell. Hence there are multiple copies of mitochondrial DNA (mtDNA) within all living cells.There are only two copies of nuclear DNA (nDNA) within each cell. Mitochondria turn the carbohydrates and fats we eat into carbon dioxide (CO2) and adenosine triphosphate (ATP), or useful energy, in a process called oxidative phosphorylation. Oxidative phosphorylation includes the citric acid cycle and both are part of classical biochemistry and are sources of early interest in the mitochondrion. During evolution, mitochondria lost many genes to the host cytoplasm. Human mitochondria now have only 37 genes.Douglas Wallace has said it was the small size of the human mitochondrial genome that inspired him to investigate it, while everyone else in graduate school was hoping to work on an aspect of the Human Genome Project. That project had been proposed in order to completely elucidate the human nuclear genome: a challenge of approximately 20,000 genes versus only 37.Moreover, as he studied and worked, it was becoming more clear to him that the one-gene-one-disease theory regarding the nuclear genome was failing to meet expectations. Some investigators said it might be interactions of two or more gene mutations that explained intransigent human diseases. However, Wallace was convinced that nuclear genes, singly or in concert with others, were unlikely to explain the diseases that concern us most in the developed world, the diseases of aging such as Parkinson's disease, Alzheimer's disease, and cancers. After all, his thinking was apparently, your nuclear genome defines the body you are born with. Something else appears to be involved when debilitating change takes over in middle age.In his career of, now, approximately four decades, Wallace has devoted his research to discovering the precise causes and possible cures of mitochondrial disease. Early in his career, he built a department devoted to the study of genetics and molecular medicine at Emory University in Georgia where he began on the faculty by teaching biochemistry. Subsequently, he moved to the University of California at Irvine where he built up an institute devoted to studying mitochondrial disease. Ultimately, he was invited to Philadelphia to build and lead the Center for Mitochondrial and Epigenomic Medicine at the Children's Hospital of Philadelphia.