The Metabolic And Molecular Bases Of Inherited Disease, 4 Volume Set

The Metabolic and Molecular Bases of Inherited Disease, 4 volume set

From The New England Journal of MedicineThe first impression this book makes is one of hugeness: it is huge in size, huge in scope, and huge in vision. This set of volumes, which weighs in at 16 kg (35 lb) and is too large to carry to one's car without advance planning, is no vade mecum. In the preface to this edition, there is mention of an informal survey of owners of the seventh edition, of whom 70 percent used the book at least weekly. This book has become indispensable to those in the field, as well as to a much broader audience. Does this edition build on the achievements of the previous seven?The first edition, then titled The Metabolic Basis of Inherited Disease, was designed to give clinicians and scientists a foundation in a field that seemed at last to be occupying an important place in medicine. Prefaces to books give insight into the editorial rationale behind them. In this eighth edition, the prefaces to the sixth and seventh editions are reprinted, perhaps because the direction of the book has changed. The editors of the earlier editions were the redoubtable team of Stanbury, Wyngaarden, and Frederickson, who were later joined by Goldstein and Brown. With the sixth edition came a change in editorship and a widening of the scope in recognition of the importance of molecular genetics. Also, for the first time, there were chapters on chromosomal disorders, Down's syndrome, and the fragile X syndrome, which the new editors realized ``might be the thin end of a very big wedge.'' So it has proved. For the seventh edition, the title was changed to The Metabolic and Molecular Bases of Inherited Disease, signaling the inexorable rise of molecular genetics as an important consideration in all aspects of inherited disease. The changes in the current edition are even more striking.Early on in the study of inborn errors of metabolism, we all came to realize what Garrod had known a half century or more before, that such research illuminates normal biochemistry. Now we have a broader field and what the editors call ``the ultimate guidebook for individualized medicine.'' Among the 225 chapters (with more than 500 authors) are, for example, 44 chapters on cancer, composing 10 percent of the whole book, as compared with 6 chapters in the previous edition and none before that. ``Cancer,'' note the authors in the introduction to these chapters, ``is in essence a genetic disease.'' This statement is an indication of the change in direction and the expansion of scope of this great textbook. It has grown from the original notion of inborn errors -- those very rare, arcane aminoacidopathies and organic acidemias with biochemical pathways that ordinary physicians shrank from exploring -- to encompass the whole of medicine that can be related to ``mutation.'' And that really means almost all of medicine. Our susceptibility to many disorders, even some accidents, and certainly infections, is influenced to some extent by our genetic makeup. For example, work in Nepal has identified a genetic background of the susceptibility to reinfection by roundworms. So where should this book go next?There are many new chapters in this edition, apart from the increased coverage of cancer. The general chapters in the first volume are useful and enlightening. The first chapter by the four primary editors is a thoughtful account of the unifying themes of the book -- in particular, its focus on diseases caused by mutations and its emphasis on the pathogenesis of various disorders, which is explored in this and previous editions in satisfying detail. A third unifying theme, therapies for inherited diseases, is developed in an excellent later chapter in which the effectiveness of various treatments is analyzed. In a chapter on pharmacogenetics, the authors use three topics to illustrate the subject and do not pretend to be all-encompassing. The inclusion of a chapter on aging is perhaps slightly surprising, but the presence of one on mouse models of huma