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Mighty Mitochondria

Published on
May 31, 2013

What causes disease? Why do we get sick? Douglas Wallace’s answer could spark a revolution in medical thinking.

For thousands of years, practitioners of Eastern medicine have linked human health to the concept of energy, or “qi” — its presence, absence and flow through our bodies affecting everything from heart disease to mental clarity. Ironically, Douglas Wallace, PhD, one of CHOP’s most internationally renowned experts in Western medicine, has spent his career proving that they just might be right.

Wallace studies mitochondria, tiny structures that serve as our cells’ “power plants,” converting food and oxygen into energy. Mitochondria are actually symbiotic bacteria that invaded our cells more than 2 billion years ago. Each of the body’s 100 trillion cells contains hundreds, or even thousands, of mitochondria, and each generates about 0.2 volts of potential energy — accounting for 90 percent of the energy the body needs. The health of our mitochondria, Wallace hypothesizes, is our health.

In fact, Wallace passionately believes a whole spectrum of human disease — everything from diabetes to autism to obesity — is caused or influenced by the mitochondria. It is nothing short of a revolution in medical thinking, and as the evidence mounts, the world is taking note.

“I really believe that life is about the interplay between anatomy and energy. Without energy, everything stops, so why shouldn’t that be the most important thing?” asks Wallace, who came to CHOP in 2010 as the director of the newly created Center for Mitochondrial and Epigenomic Medicine. “This is the vital force that people have been wondering about for probably three to 5,000 years. And it’s a straightforward biophysical process.”

Wallace founded the field of human mitochondrial genetics in the late 1970s when he and his team made a fundamental discovery: Mitochondria, which have their own unique DNA (often abbreviated mtDNA) that is separate from the DNA in the nucleus of our cells, are inherited only from our mothers. Completely unchanged from mother to child, your mtDNA is the same as your mother’s mother’s mother. This remarkable discovery allowed Wallace to trace 200,000 years of human migration patterns around the world.

In November, the Gruber Foundation awarded Wallace its prestigious Genetics Prize for his work in mitochondrial genetics, but for decades, he worked under a cloud of skepticism from the scientific community. That began to turn around about 20 years ago when he published two landmark papers demonstrating that glitches in mtDNA cause disease.

Even the smallest variation in mtDNA can cause a subtle change in mitochondrial energy output. Multiplied by trillions of mitochondria, this can have a tremendous impact on the body, particularly the brain, which requires more mitochondrial energy than any other organ. Leigh syndrome, for example, is a severe neurological disorder caused by a mutation in mtDNA.

While diseases like Leigh syndrome are rare, a stunning paper published in Cell in October indicates that even common neurological conditions, even something as simple as learning disabilities, may connect to the mitochondria. Wallace’s study showed that by combining two normal mitochondrial DNAs in the laboratory mouse resulted in neurological disorders and learning problems.

This finding may shed new light on one of the most common and most mysterious childhood disorders, autism, which affects 1 in 88 American children. Wallace says autism fits the profile of mitochondrial diseases: It is a subtle neurological problem in brain function that disproportionately affects boys more than girls and is sometimes accompanied by gastrointestinal problems, immunological problems and other issues that might result from a lack of mitochondrial energy.

“We might have a real window into helping a lot of kids that have trouble in school or have problems with behavior,” Wallace says.

Wallace and his team are currently developing diagnostic tests that can more easily detect mitochondrial defects, using nothing more than the patient’s breath blown into a can. He feels a strong sense of mission to change the way people think about medicine because the resulting treatments for disease could be game-changing for human health. He sees connections to mitochondria in everything from heart disease to obesity to diabetes to Alzheimer’s disease.

“We’re on the verge of a major revolution of medicine,” Wallace says. “We’re going to change from an anatomically based medicine to an energetically based medicine, and more than half of all the complex diseases that we’re worried about right now may be solved that way.”

From the latest issue of Children’s View.