Wayne W. Grody - Molecular Diagnostics: Techniques and Applications for the Clinical Laboratory

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Foreword

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Molecular diagnosticsmolecular pathologygenomic medicine: It wasnt all that long ago when these terms were unknown in the medical lexicon, and in fact would have sounded at best unintelligible to most practitioners, or at worst like oxymorons. But the last 20 years have seen, at last, the long-promised marriage of molecular biology with clinical medicine, with a consequent explosion in molecular test volume and variety, and broad awareness of their existence among both physicians and the lay public. It is now unusual to read a paper in any of the major medical journals that does not include some molecular procedure in its Materials and Methods section, while a new generation of journals, books, and professional societies devoted entirely to molecular diagnostics has emerged.

Why, then, the need for another book on this subject? Perhaps it is not so much related to substance as to perspective. At risk of betraying our ages, the editors of this volume have lived through, in their careers, virtually all of the revolutionary advances and discoveries in modern human molecular biology: the discovery of bacterial restriction enzymes and the birth of recombinant DNA technology; the development of the Southern blot and the polymerase chain reaction; the advent of instruments for automated and now next-generation DNA sequencing, along with high-density oligonucleotide microarray hybridization; the discovery, counter to any intuitive logic, that eukaryotic genes are broken up by interspersed noncoding segments that are much longer than the coding sequences; the appearance of a novel human retrovirus that directly attacks the immune cells that are supposed to fight it and has spread worldwide and caused the deaths of tens of millions; the identification of a human-encoded protein that, when misfolded, destroys the brain and propagates like an infectious microorganism even though it contains no nucleic acid; the recognition that cancer can be a genetic disease, and the discovery of cancer predisposition genes that are inherited; the recruitment of human DNA polymorphisms for mapping of disease genes and DNA fingerprinting; the discovery of small noncoding RNAs that may in fact be the master regulators of gene expression; and, last but far from least, the launch and completion of the Human Genome Project.

If nothing else, these discoveries should impart a sense of humility, if not outright anxiety, among all who study and work with them. For it is apparent that the complexity of human molecular biology is many orders of magnitude beyond that of the bacterial operon-promoter-repressor model that many of us were weaned on; and that every question answered only raises a hundred new questions. This provides both the excitement and the challenge of modern molecular diagnostics, and we hope that this book, with its emphasis throughout on the newest and impending approaches and applications, will impart such a sensibility to both novice and seasoned molecular diagnosticians.

Chapter 1. Quantitative PCR

Department of Pathology, Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48201