The news broke today that Philadelphia’s own medical pioneer Douglass Wallace will win the $500,000 Gruber Prize for genetics. He’s enlightened the medical world about the importance of a cellular structure that powers cells and makes complex animal life possible. That structure is called the mitochondria, and it’s known to have its own DNA. When that DNA is mutated or damaged, the effects can be deadly.
Wallace holds joint appointments at CHOP, where he directs the Center for Mitochondrial and Epigenomic Medicine, and at Penn. I met him in 1997, when the concept of mitochondrial medicine was just starting to emerge. Here’s an excerpt from my story back then:
Though the first case of a mitochondrial disease was diagnosed in 1962, it was not until the mid-1980s that doctors began to recognize more cases in children. Experts now suspect that many patients are wrongly diagnosed as having cerebral palsy, epilepsy, multiple sclerosis, or ``failure to thrive. '' It may even account for instances of sudden infant death syndrome.
``We need to convince [doctors] these disorders are common and important,'' said Douglas Wallace, an Emory University biologist attending an international meeting on mitochondrial diseases held this month in Philadelphia.
``Until recently, it was considered stupid to look at the mitochondria'' as a cause of disease, says Wallace. The changing attitude took a revolution in scientists' understanding of these tiny cellular power plants.
High school textbooks have long depicted the mitochondrion as a folded ribbon surrounded by an oval-shaped membrane. The snapshot was accurate but the standard definition - an organelle, or tiny organ, with the job of making energy - didn't capture its strangely independent nature.
In 1963 scientists discovered that the mitochondria carried their own set of genes, made from their own DNA. (Before that, scientists thought all human DNA was contained in the 23 pairs of chromosomes inside the cell's nucleus. )
The genes in the mitochondria pass only from mother to offspring - egg cells carry mitochondria, while sperm cells do not. Stranger still, some scientists have come to see the mitochondria not as a standard part of our bodies but as a life form in itself - a benevolent parasite.
The way Wallace explains it, about a billion and a half years ago, a slender, thread-like bacterium slithered inside a larger one-celled organism. Both life forms benefited from the invasion. The bacterium gained the protection and mobility of its much larger host, and the host benefited by absorbing some of the energy that the invader pumped out. The invader used an efficient, oxygen-burning process that the host cell had not evolved.
This mutually beneficial - or symbiotic - partnership worked so well that the two evolved together into fungi, plants and animals. The discovery of the mitochondria's own set of genes backed this scenario of an independent origin, especially after analysis showed that the mitochondria's closest relative is a free-living bacteria.
Wallace argues that, as composite beings, we can die one of two ways - either the body's cells die, or the mitochondria within them die.