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Howard A. Young, PhD

Section Head, Cellular and Molecular Immunology Section, Laboratory of Experimental Immunology, National Cancer Institute, NIH

REVIEW

Dr. Hanan Polansky has taken theoretical biology to a new level with his book, Microcompetition with Foreign DNA and the Origin of Chronic Disease. In this book, Dr. Polansky develops his hypothesis that through the introduction of foreign DNA into cells via viruses, there is competition within the cell for specific transcription factors. This competition significantly alters gene expression, especially of the Tissue Factor gene, resulting in the triggering of many chronic diseases, including cancer. The hypothesis is of significant interest and will not
be foreign to today's molecular biologists, as most scientists that have performed transfection experiments in tissue culture realize that competition for transcription factors may occur when two or more plasmids are co-transfected. Indeed, the rapidly growing use of interfering RNAs is in itself a form of microcompetition resulting in inhibition of specific targets. Thus the basic theory put forward by Dr. Polansky will have champions in the experimental biology community. Throughout the book, Dr. Polansky does a good job of demonstrating how existing data supports his theories. In the chapter on cancer, I found particularly interesting, Dr. Polansky's explanation that data obtained in transfection experiments with "empty" vectors in comparison to non-transfected cells, showing higher growth rates and tumor volumes, is due to the microcompetition from foreign DNA (i.e. the empty vector) through sequestering of p300 and resulting in decreased transcription of the Rb gene.

While the idea of microcompetition with foreign DNA as an explanation for all chronic diseases is intriguing, it does not address all aspects of chronic disease (e.g. why some diseases are more prevalent in females) and may be overly reductionistic in nature. Nevertheless, Dr. Polansky presents his theories in a manner that provides bench scientists with ways to test his theories experimentally, and this book will be thought-provoking for all those who read it. However, the book itself is not an "easy" read and probably is best-suited for an advanced graduate level course. Chapters need to be read a number of times for more thorough appreciation of the theories and the inclusion of numerous biological 'equations' tends to make it a bit hard to sometimes grasp the bigger picture. The book could be improved by having more simplified pathways in the beginning of each chapter to better illustrate the major hypotheses being presented.

In summary, Dr. Polansky is to be applauded for his attempt to provide a unifying basis for chronic diseases. His theories are stimulating and offer a basis for experimental testing and possible treatment. It is worth the time for the experimental biologists to consider his ideas by reading this book and determine if the theories presented will hold up to carefully designed laboratory experiments.

BIOGRAPHY

Howard A. Young received a B.S. in Microbiology from the University of
Massachusetts and his PhD from the Department of Microbiology, University
of Washington. He joined the National Cancer Institute in 1983 as a Cancer
Expert in the Laboratory of Molecular Immunoregulation and in 1989 became
Head, Cellular and Molecular Immunology Section, Laboratory of Experimental
Immunology. He is the President-elect of the International Society of Interferon and Cytokine Research (term 2004-2005) and is a member of the American Association of Immunologists, the American Association for the Advancement of Science, the American Society for Biochemistry and Molecular Biology, the American Society for Microbiology and the DNA Methylation Society. He has received an NIH Merit Award for his efforts in support of the Werner Kirsten Student Intern Program, the NCI Quality of Worklife Award (1999) and the NIH Director's Award for Mentoring (2000). He has chaired the NIH Cytokine Interest Group, the NCI-Frederick-Ft. Detrick Spring Research Festival and the Immunology Division of the American Society for Microbiology (1997-1998) and currently co-chairs the NIH Immunology Interest Group. His research focuses on the regulation of gene expression in the immune system with a special emphasis on Natural Killer cells.

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