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Lloyd E. King, Jr., MD, PhD

Professor of Medicine (Dermatology), Vanderbilt University School of Medicine

REVIEW

The hypotheses put forward by Dr. Hanan Polansky are intriguing once the complexities of the data presented are analyzed by an initial perusal and a subsequent thoughtful review. Connecting biological, genetic and clinical evidence lead him to construct a conceptual framework of how interacting elements regulate susceptibility, severity and sustainability (chronicity) of human diseases. A fundamental law of interacting forces is a critical limiting element and competition for it in a system determines the ultimate direction and speed of the process, the "rate-limiting step." In economic theory the "rate-limiting step" often is the availability of capital or resources as determined by multiple interacting forces. In biochemical reactions the availability of a critical substrate or the enzyme responsible for generating that substrate is a "rate-limiting step."  In molecular genetic terms the availability of a critical binding site in DNA and/or RNA determines the activation or inactivation of a "rate-limiting step." Professor Polansky proposes that "p300/GABP N-box" interactions are such "rate-limiting steps." Competition for these sites determines the susceptibility, severity and sustainability involved in selected human chronic diseases states. He does not extend his analyses of "p300/GABP N-Box" interactions in chronic human diseases to the molecular genetics of embryology per se. However, "rate-limiting steps" are always involved in these processes along with the asymmetric spatial and temporal generation of regulatory signaling molecules. The value of Dr. Polansky's hypothesis is that it can be validated or refuted. "p300/GABP N-box" interactions occur in multiple, experimentally manipulatable single and multiple cell organisms, not just human tissues in vivo and in vitro. How his hypothesis may elucidate the multiple genetic and environmental factors that predispose or make an individual 'susceptible' to chronic diseases such as cancer, alopecia and the aging process is truly speculative at this point. His hypothesis provides a different and simplified perspective to understand Darwin's hypothesis of survival and adaptability. Hopefully Dr. Polansky has found the "Golden Fleece" and not the Siren's song to reduce complex biological systems to permit comprehensible (erroneous?) analyses. Whatever the ultimate outcome, I recommend his book as a thoughtful, in-depth analysis of seemingly unconnected data to provoke thoughtful discussions by an equally diverse audience.

BIOGRAPHY

Dr. Lloyd E. King, Jr. received a B.A. in Math from Vanderbilt University in 1961, and an MD in 1967 and a PhD in 1970 from the University of Tennessee, Memphis, TN. From 1968-1969, he worked as a Postdoctoral Fellow in the Department of Anatomy, University of Tennessee Medical Units; from 1971-1976, Instructor, Department of Anatomy, University of Tennessee Medical Units; from 1972-1974, Clinical Associate, Dermatology, VA Hospital, Memphis, TN; from 1973-1976, Instructor, Department of Internal Medicine (Dermatology), University of Tennessee Medical Units; from 1974-1975, Leon Journey Fellowship in Biomedical Research and NIH Special Postdoctoral Fellowships Biochemistry of Cell Membranes, St. Jude Children's Research Hospital, Memphis, TN; from 1975-1977, Assistant Member (Biochemistry) St Jude Children's Research Hospital; from 1976-1977, Assistant Professor, Departments of Internal Medicine (Dermatology) and Anatomy, University of Tennessee Center for Health Sciences; from 1977-1982, Associate Professor of Medicine, Chairman, Division of Dermatology, Department of Medicine, Vanderbilt University Medical Center; from 1977-1987, Chief of Dermatology, VA Medical Center, Nashville, TN; from 1982-2002, Professor of Medicine, Chair, Dermatology, Vanderbilt University, Nashville, TN; from 1987-2003, Staff Physician, Director, Photopheresis Center DVA Medical Center, Nashville, TN; and from 1997-2003, Director, VA Dermatology Diabetes Foot Care Clinic. Currently, Dr. King is a Professor of Medicine (Dermatology), Vanderbilt Dermatology, Nashville, TN. Dr. King has been a committee member of a number of organizations throughout his career. In addition, he has published 209 papers, 42 chapters, and 112 abstracts. In the late 1970s, Dr. King collaborated with Stanley Cohen, PhD, who went on to win a Nobel Prize in medicine in 1986. 

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