Researcher says cancers, other illnesses stem from structures that provide cells energy. The Orange County Register (Santa Ana, Calif.) (via Knight-Ridder/Tribune News Service); 2/6/2005 Byline: Mayrav Saar SANTA ANA, Calif. _ Doug Wallace's pants are too big. They're held up by suspenders that peek out from beneath his oversized jacket. His hair is too long, falling on top of his too-big glasses. He is not a large man, but his gestures are so grand, his charisma so great, he seems to fill the big space he's created. What he's saying right now is pretty odd, pretty fringe. But Wallace is used to being fringe. He's made a career out of the fringe. If he's right, Wallace could change the way we understand, prevent and treat cancer. His work has the potential to slow or stop Alzheimer's disease and Parkinson's. If he's wrong, Wallace would have spent 30 years studying tiny structures at the outer edges of cells that do little more than serve as the catering service to the nucleus. But he's pretty sure he's right. "I think the world is on the wrong track," said Wallace, 58, a self-described missionary of mitochondrial DNA research. The room full of scientists and students at UC San Diego consider him with genuine interest. But if this is Wallace's revival tent, it's not clear how many converts he has. For nearly two hours, the UC Irvine professor tells the crowd that the genes inside a mitochondrion are the real predictors of disease, as opposed to the nuclear DNA that most researchers evaluate. Whether a person is predisposed to develop Alzheimer's disease or Parkinson's or other age-related ailments, as long as that mitochondria is healthy, we'll stay healthy. Hands shoot up after his lecture. The assembled scientists and medical students at UCSD want to know the particulars about what the small man with the big ideas has been talking about. Does mitochondrial damage accumulate in human eggs? Is each generation getting sicker? How does this play out in a clinical setting? After a handful of questions, Immo Scheffler takes the stage. Scheffler, a professor of biology at UC San Diego who has also studied mitochondrial mutations, invited Wallace to speak. He'll say later that the lecture was interesting, but not entirely convincing. Now, though, he tells the crowd that Wallace can only take only one more question before being whisked off to prepare for a second lecture later that evening. "Oh! I love it!" Wallace says, like a kid begging to stay longer at a friend's house. "Anytime I can proselytize about the mitochondria, I'll do it!" And he does do it. In disease research, in biological evolution, in anthropology. There are few places Wallace hasn't been able to find the magic of the mitochondria. In each of these fields Wallace is regarded like the mitochondria he studies: A powerhouse whose work is either inordinately important or not much more than interesting, depending on whom you ask. There are, after all, only 37 genes in the mitochondria, which isn't much. The nucleus has 20,000 genes. That's 20,000 genes that could mutate and cause a cell to die or run amok with cancer. If the nucleus has 20,000 genes, it's where scientists should be looking to find the causes _ and it is hoped cures _ to every human disease. Except it's not. Or, at least, it's not to Wallace. It's quite obvious to Wallace: The mitochondria work like power plants. The nucleus might be the center of the city, but the power plants, operating outside, allow the city to run. If the blueprints are sound and the contractors built them well, all will be fine. But if the contractors were lazy or sloppy, the power plants would spew smoke into the air, sputter and fail. The city would go dark, and all would collapse into chaos. Wallace gives this analogy, speaking with such certainty you come away believing he's either completely right or completely crazy. He knows that he gives off those two impressions. But, again, he's pretty sure he's right. And if the majority never sees it his way? Well, Wallace and his wife, Betty, 57, are Unitarians, so Betty says they're used to being on the fringe. Their son, David, has high-functioning autism. And when their daughter, Lisa, was found to have a slight learning disability, Betty said she and Doug comforted her by saying, "If you were mainstream, we'd have to do a DNA test to make sure you were ours." Dr. Sue Bryant, dean of UC Irvine's school of biological sciences, who helped recruit Wallace to UCI from Emory University in 2002, describes him as "one of a kind." "We're just coming out of that place where everything is focused on the structure of DNA. It's all been focused on the nucleus and on nuclear genes," she said. "So it's so interesting that he didn't follow that paradigm." Wallace began studying the mitochondria in 1970, when, as a graduate student at Yale, he realized nuclear DNA was terrifically boring stuff. Who cares about mapping a gene on a chromosome? He wanted to study something that actually did something. He figured the mitochondria were a good bet: Anything that produced 90 percent of the body's energy and contained complicated genes had to be significant. Right? At the time virtually no one studied the importance of mitochondrial DNA mutations. Now, 30 years later, after Wallace and his colleagues found mitchondrial DNA can mutate, after he found those mutations can cause diabetes and heart disease, after tracing mitochondria's thumbprints all over tissue cancers ... virtually no one studies the importance of mitochondrial DNA mutations. Wallace chalks up the spotty interest to mitochondrial DNA being more complicated to study than the much-longer DNA chains of the nucleus. Other researchers, though, say their colleague is simply overstating the significance of his work. "Doug rubs some people the wrong way by claiming to have found the solutions when really there are more questions out there we need to solve," Scheffler said. "Until 10 years ago, people definitely ignored mitochondrial DNA in human health and disease. "Now they realize that paying attention to that small DNA is important, but the fact that we should pay so much more attention to it is something I don't agree with." This could change. When UCI hired Wallace, it started the Center for Molecular and Mitochondrial Medicine and Genetics and named him director. His research is cited in fields as far-flung as anthropology and evolutionary biology. A recent study of his, published in the Proceedings of the National Academy of Sciences last month, shows a link between mitochondrial DNA mutations and prostate cancer. He's using that link now to test non-toxic drugs to kill prostate cancer in mice. "People generally agree that he is a world leader in mitochondrial DNA issues," said Bill Parker, dean of graduate studies at UCI. "Should that field at some point, be considered for a Nobel Prize, he'll be right in the center of it." The center? What an odd place for Wallace to be. ___ (c) 2005, The Orange County Register (Santa Ana, Calif.). Visit the Register on the World Wide Web at http://www.ocregister.com/ Distributed by Knight Ridder/Tribune Information Services. _____ PHOTO (from KRT Photo Service, 202-383-6099): For information on republishing this content, contact us at (800) 661-2511 (U.S.), (213) 237-4914 (worldwide), fax (213) 237-6515, or e-mail reprints@krtinfo.com. COPYRIGHT 2005 The Orange County Register