Genetic Cartography

The idea of being able to map out mitochondrial lineage in order to find the best mtDNA donors for therapeutic cloning is a heady one. UC Irvine's Center for Molecular and Mitochondrial Medicine and Genetics has spent the last three decades mapping out the genetics of the mitochondrial DNA. In essence, it's acted as a sort of a Human Genome Project for mtDNA.

The underlying direction of the research is to determine the causes of many of the common age-related degenerative diseases, which could be alleviated by therapies developed from stem cell technology. Up until now, these causes have been extremely difficult to resolve.

Wallace is adamant that this difficulty is simply the result of the fact that researchers were only looking at the DNA of a cell's nucleus. They did not, or not sufficiently, look at the contents of the mitochondrial DNA, he insists. "Since the mitochondrial DNA has a totally different inheritance system, a totally different interaction because it makes thousands of copies, and because it has a key function of providing energy, they may have missed the very factor that they were looking for."

Wallace's views may again be simply ahead of the curve. The evidence in his favor is slowly accumulating. One of his latest studies, which was published by the National Academy of Sciences, shows a distinct correlation between mutations in a cell's mito-chondrial DNA mutations and the development of prostate cancer.

Despite this development, there is a strange reluctance in the wider scientific community to pursue this line of research further. For all the effort spent on genetic research, it is strange that this second set of cellular blueprints is relatively ignored as candidates for possible cures—or causes—of serious illness.

Doug Wallace attributes the lack of interest to a phenomenon discussed in the book Structure of Scientific Revolutions by Thomas Kuhn. In it, Kuhn argues that scientific advancement is not evolutionary, but rather is a "series of peaceful interludes punctuated by intellectually violent revolutions." In each revolution, one conceptual world view is simply replaced by another. In astronomy, it could be argued that the transition took place when the scientific community broke from the Aristotelian way of looking at things to the Copernican view. In biology, it was the acceptance of the germ theory as the cause of disease and infection. And in physics, it was the shift from Newton to Einstein.

Additionally, Kuhn's book makes the point that people are predisposed to developing paradigms as a way of structuring information, even though the paradigms are potentially incomplete. Unfortunately, once enough people have agreed upon a paradigm and it has predictive value, they come to believe that it is, in fact, complete. It becomes exceedingly difficult to ask a question outside the accepted framework.

In the case of genetic research, the prevailing paradigm is that all important information is in the nucleus. However, should stem cells yield the potential for creating new tissues and organs to allow spinal-cord patients to walk again or to replace failing kidneys, then the mitochondrial barrier—and how to surmount it—will take center stage. Bill Parker, dean of graduate studies at UC Irvine, puts it very aptly. "Should that field at some point be considered for a Nobel Prize, [Doug Wallace] will be right in the center of it."

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