The History of a Genetic Disease: Duchenne Muscular Dystrophy or Meryon's Disease (review)

This is an excellent account of both classic and recent advances in the pathogenesis of Duchenne muscular dystrophy. The subtitle of this book, “Duchenne Muscular Dystrophy or Meryon’s Disease,” is a very good indication that Meryon had an essential role to play in the elucidation of the pathology and genetic predisposition of this disease. In Meryon’s work, first published in 1851, the entity that we recognize as Duchenne muscular dystrophy was first described on histopathological grounds, and the definite maternal genetic carrier state was put forward. Concurrent with Meryon’s efforts were those of a French neurologist, Duchenne de Boulogne, whose description in the 1860s was far more detailed. As pointed out by the authors, Duchenne had made many significant contributions to neurology—including the use of electricity in diagnosis, and the descriptions of progressive bulbar palsy and partial brachial plexus palsy—and had provided one of the earliest detailed accounts of tabes dorsalis. With this as a background, it seemed reasonable at the time to give the eponym of Duchenne muscular dystrophy to this disorder.

The recognition of other muscular dystrophies and the resolution of the heterogeneity of these diseases is well characterized in the middle chapters of this book. A number of investigators are cited—specifically, Sir William Gowers (whose clinical description of the disease has not been improved upon since his publication on “pseudo-hypertrophic muscular paralysis” in Lancet in 1879), and Dejerine, Milhorat, Nattrass, and Morton, whose contributions to muscular dystrophy are outlined in a succinct, well-documented fashion. The references in this volume are provided in a chapter-by-chapter series at the end of the volume, and portraits of all those cited are provided in the text.

Following an outline of the biochemical diagnosis and carrier detection of this disorder featuring the use of Bayesian statistics, first introduced by Murphy in 1966, the Emerys then touch on the most recent events in this amazing story, culminating in the description by Louis Kunkel of the isolation of the Duchenne gene in 1985, with a complete description of the cloning of the Duchenne gene in 1987. The authors are very fair in detailing the contribution of another group headed by Ronald Worton in Toronto, whose paper was submitted only months after the submission of the Kunkel manuscript. By reverse genetics, the gene for dystrophin, its molecular weight, and its sequence of 3,685 amino acids were derived; as the Emerys state, it is unlikely to have ever been identified by more conventional biochemical techniques, since dystrophin comprises only 0.002 percent of muscle protein, and thus the complete story is a triumph for reverse genetics. Many of the recent advances have occurred because of the consuming interest of various laboratories, and because of an extraordinary generosity on the part of some of these laboratories to share their data prior to publication, including antibodies and molecular sequences.

This is an exciting book. It grips the reader from the very start and is a superb example of how a study in the history of one disease entity that includes discussion up to the present time can take the reader on a marvelous journey from the first recognition of that disease in the late eighteenth and early nineteenth centuries to the complete description of the gene and gene products responsible for this disorder in the last decade. This book is highly recommended to readers interested in the history of medicine, but especially to those interested in neurology, muscle disease, and the pathophysiology of genetic diseases.