Scientific American Molecular Neurology

From The New England Journal of MedicineMolecular biology began as a scientific discipline with the discovery of the double helical structure of DNA by Watson and Crick in 1953 and the establishment of the complete genetic code by Nirenberg in 1966. In rapid succession came the discoveries of the first sequence-specific restriction endonucleases, recombinant DNA molecules, plasmid vectors for cloning, identification of specific DNA sequences by the Southern blot technique, DNA-sequencing methods, genetic-linkage analysis, positional cloning, and the polymerase chain reaction. These molecular methods have entered the clinical arena with great success and have provided molecular insights into the mechanisms of disease that were undreamed of just 35 years ago.Molecular neurology as a discipline owes its birth and existence to these molecular approaches. Francis Collins, the director of the Human Genome Project at the National Institutes of Health, estimates that 3 to 4 percent of the 3 billion nucleotides in the human genome have been sequenced. Thus, we have detailed information on a limited number of the 70,000 to 80,000 genes expressed in a human cell, including the neurons and glia of the brain. Despite the relatively small amount of genetic information at our disposal, enormous progress has been made in deciphering several major neurologic diseases with the use of these methods.Great credit must be given to Joseph B. Martin among a small group of neurologist-neuroscientists who recognized in the late 1970s and early 1980s the importance of molecular biology for elucidating the mechanisms of neurologic disease. His enormous influence in bringing the field of molecular neurology into being in a rather short period is evidenced in his organizing and editing of Molecular Neurology. Every area of molecular analysis of neurologic disease included in this well-written and beautifully illustrated book provides evidence of his positive and catalytic efforts at Harvard and the University of California at San Francisco.The book contains 15 chapters by 21 authors, 15 of whom are faculty members at Harvard or the University of California at San Francisco and have worked closely with Martin for many years. The clarity and immediacy of the exposition of theory and data throughout the book are testimony, in my view, of Martin's excellent editing and personal knowledge of the authors' fields and qualities.The editor enhances the book by including a foreword and an epilogue, which outline his orientation and rationale for the book and ideas for future research. These features unite the central theme and give the book added cohesion. James Gusella and Joseph Martin begin the book with a clearly worded chapter on the principles of neurogenetics that provides the definitions and explanations of technical advances needed by the reader. The chapters "Huntington's Disease and Other Trinucleotide Repeat Disorders" by Anne Young, "The Molecular Genetics of Alzheimer's Disease" by Rudolph E. Tanzi, "Genetics of Epilepsy" by James McNamara, "Molecular Genetics of Brain Tumors" by Mark Israel, "Molecular Neurology of Prion Diseases" by Stanley Prusiner, "The Molecular Pathogenesis of Multiple Sclerosis" by Jorge Oksenberg and Stephen Hauser, "Amyotrophic Lateral Sclerosis and Inherited Motor Neuron Diseases" by Robert Brown, and "Molecular Genetics of Peripheral Neuropathies" by James Lupski stand out as brilliant expositions in which the molecular data are clearly and succinctly expressed and future directions of investigation become real and understandable.The descriptions of potential pathologic mechanisms as suggested by the molecular data are important features, because they make clear to the reader the way in which the author conceives the molecular pathogenesis of disease, giving an unexpected but very welcome insight. I found Anne Young's discussions of protein-protein interactions very compelling explanations of the way in which the CAG-