The Center for the Biology of Chronic Disease

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Kim E. Barrett, PhD

Professor of Medicine and Vice-Chair for Research, Department of Medicine, University of California, San Diego, School of Medicine

REVIEW

Microcompetition with Foreign DNA and the Origin of Chronic Disease by Hanan Polansky is a provocative and challenging contribution to our understanding of a large number of hitherto mostly unconnected disease states. It rests on a single basic premise – that the existence in the body of specific viral gene sequences competes for an important transcription factor, and by doing so, alters expression of genes that are both positively and negatively regulated by this factor. This so-called "microcompetition" thereby gradually leads to a new steady state for a variety of biological processes that we recognize eventually as disease.

Many diseases that were not previously suspected as being due to infectious processes are emerging as being caused by bacteria and viruses. Thus, the guiding hypothesis in this book is perhaps not wholly novel. However, what is new is the massive extent of the dataset that Dr. Polansky has marshaled to support his arguments, and the rigorous quantitative analyses and modeling he has applied. Likewise, the concept that we should think about chronic viral infections in terms of their protein independent effects represents a paradigm shift that may have important implications for understanding such disease states. These effects also imply a potential ability of viral pathogens to alter host biology in such a way as to cause disease, while yet evading host immune defenses that are directed predominantly towards the protein products of the virus.

The most powerful aspect of this book is that it establishes a series of testable hypotheses. Even if only a portion of the author's thesis is correct, it would establish wholly new insights into the pathogenesis of chronic disease states, and would have significant implications for treatment and/or prevention. At the very least, the author's constructs do raise a note of caution for molecular biologists in assessing the results of transfection experiments. Thus, transfection with an 'empty' vector may not be the innocuous control condition that is commonly assumed if the concepts of microcompetition are validated.

BIOGRAPHY

Dr. Kim Barrett received her PhD from University College London in 1982, for studies that elucidated the extent of functional heterogeneity among mast cell populations in different organs. Following postdoctoral training at the National Institutes of Health, she joined the faculty of the University of California, San Diego, School of Medicine, in 1985, where she is now Professor of Medicine and Vice-Chair for Research in the Department of Medicine. Her research interests have centered on the intestinal epithelium as a critical interface between the host and environment, and implications of epithelial signal transduction for the control of transport and barrier functions. Her work has been supported by continuous funding from the National Institutes of Health, and she has also received funding from the Crohn’s and Colitis Foundation of America. Her findings have shed light on pathogenetic mechanisms underlying infectious diarrheal diseases, cystic fibrosis, and inflammatory bowel diseases, as well as the mechanism underlying beneficial effects of probiotic microorganisms. Her accomplishments have been recognized with several prestigious awards, including the Bowditch Lectureship of the American Physiological Society, the Young Investigator Award of the American Gastroenterological Association and the Gastroenterology Research Group, and the McKenna lectureship of the Canadian Association for Gastroenterology. She has also been the recipient of awards for her contributions to medical and graduate education. Finally, she served a six-year term as Editor-in-Chief of the American Journal of Physiology – Cell Physiology, and is a current member of several additional editorial boards worldwide.

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