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Janice M. LaPlante, PhD

Research Fellow, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital

REVIEW

In his book, Microcompetition with Foreign DNA and the Origin of Chronic Disease, Dr. Hanan Polansky presents a novel theory that links a number of chronic diseases to the presence of foreign DNA in the aging cell. He postulates that DNA sequences that are foreign to the cell, sequences which, in-and-of- themselves may be inert, bind to and titrate transcription factors that are present in limiting quantities in the cell. These foreign sequences include viral promoters, germline or inherited mutations and endogenous sequences that have undergone somatic mutation. All cells are elegantly regulated by transient adjustments in gene expression in response to stress and other stimuli. The initial stimulus leads to the activation of a few key transcription factors, each of which goes on to activate entire regimens of genes whose protein products enable the cellular response. In order to achieve a fine-tuned level of regulation, the response must be proportional to the stimulus. Thus, the key transcription factors must be present in limiting molecular quantities. Polansky's Theory of Microcompetition presupposes that within a given cell, the presence of a few additional sequences capable of binding to these limiting factors will efficiently compete with their endogenous target promoters, thereby disrupting the balance of downstream gene expression. Polansky suggests diverse mechanisms built on the same theme to explain a range of chronic diseases of aging including atherosclerosis, autoimmunity, obesity, osteoarthritis, cancer and alopecia. His extensive supporting arguments, including incidental data and complex mathematical formulae are quite compelling. The mechanisms that he proposes are original, interesting and amenable to testing. Although it is unlikely that scientists will ever discover a single trigger for the onset of "aging," Polansky's theory is notable because it provides a potential basis for the relationship between various aging phenotypes and environmental factors such as viral infection and exposure to mutagens. The theory is especially relevant to phenotypes that manifest gradually or aren't triggered until many years after the initial insult.

In addition to the concepts that Polansky deals with directly, this book provides a unique foray into the intricate mind of a philosopher, continually challenging the reader through an adventure of the intellect.

Although specialists from a number of diverse fields would appreciate sections of the book relevant to their own work, the beauty of this theory is that it crosses many of the self-imposed boundaries that have traditionally limited the creative thought process. This book could make an excellent foundation for a course in "Skills for Creative Thinking" to be offered to upper level undergraduates or graduate students prior to specialization. However, because most students are likely to be novices in at least some of the areas that are covered in the book, I would recommend that the instructor provide a well-rounded introduction to each section, with a vibrant discussion guaranteed to follow.

All in all, this book makes a great read for the scientist with a far-reaching mind, one who is open to new areas of exploration but not afraid of the rigorous journey.

BIOGRAPHY

Dr. Janice M. LaPlante earned her A.B. degree in Biological Sciences from Indiana University in Bloomington, Indiana. After completing her PhD in Biomedical Science from the University of Connecticut Health Center, specializing in the study of intracellular calcium signaling, she was awarded a fellowship from the National Institute of Aging to study the molecular and cellular basis of aging at Harvard Medical School. Dr. LaPlante is currently a Research Fellow in the Division of Endocrinology, Diabetes and Hypertension at the Brigham and Women's Hospital. She is part of a multidisciplinary team of scientists from the Neurogenetics Unit of Massachusetts General Hospital and the Harvard Partners Center for Genetics and Genomics, working to clone genes that regulate intracellular calcium signaling and to study their relationship to disease. She is the Principal Investigator of a project to identify the molecular function and cellular role of Mucolipin-1, a lysosomal TRP ion channel that is involved in intracellular membrane trafficking and is the product of MCOLN1, the gene that underlies the neurological disease Mucolipidosis Type IV.

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