Microcompetition with Foreign DNA and the Origin of Chronic Disease (reivew)

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.

Bacteria and viruses are emerging as the cause of many diseases that were not previously suspected as being due to infectious processes. Thus, the guiding hypothesis in this book is perhaps not wholly novel. What is new is the massive dataset that 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 book, while provocative, is not for the faint of heart. Even those familiar with the basic concepts of the biomedical sciences, including cell biology, disease pathogenesis, and signal transduction, will find the sheer breadth of topics covered here a challenge to comprehend; this is certainly not a book that will be readily appreciated by a lay audience. In part, the difficulty relates to the style in which the material is presented. The author assumes familiarity with many topics and introduces concepts, and sometimes even abbreviations, with little or no definition. Likewise, the flow of the narrative is frequently interrupted with equations and so-called "sequences of quantitative events." While these may have aided the author in developing his overarching hypotheses, in many cases it seems that the ideas could be presented more clearly in words, and thus the symbols and abbreviations used to stand for various facets of cell signaling became, for this reader, a distraction rather than an aid to comprehension.

As noted above, one strength of the volume is the sheer mass of data that the author has reviewed to support his hypothesis. To some extent, however, this is also a weakness, as it is challenging to keep sight of the global framework when wading through the detailed materials presented in each chapter. Likewise, because the book draws from many areas of modern biology, it may not have been appropriate to use abbreviations so liberally; a standard abbreviation in one field may be totally unknown in another. At the very least, it would have been helpful to have a table of abbreviations either at the beginning or the end of the book.

Furthermore, while the ideas expounded by the author certainly have some attractiveness and merit, I was concerned that hypothetical constructs introduced in one section of the book morph into known facts in others. For example, Polansky presents an analysis showing that microcompetition with viral DNA may account for the development of atherosclerosis in the section on this topic, but in the next sections of the book, this putative causal relationship is presented as an established fact (215). Similarly, the author states that "the cause of obesity is a latent infection with a GABP virus" (268), whereas this is only a putative cause based on the foregoing discussion.

Some of the theoretical constructs also seem to be at odds with data available in the literature. For example, it is unlikely that the association between mutations in the transforming growth factor (TGF)-beta receptor and excessive cell proliferation/cancer are due to decreases in...