"I thought humanity to be inflicted with enough evils already. I do not congratulate you, sir, upon the new gift you have made it."

This melodramatic pronouncement, made by a colleague of 19th-century French neurologist Guillaume-Benjamin-Amand Duchenne, referred to Duchenne's historic description of a particularly progressive and destructive neuromuscular disorder primarily affecting boys.

For a century, the disorder would be known as pseudohypertrophic dystrophy, after Duchenne's observation of the seeming overdevelopment of calf muscles in boys with the disease. Eventually, the condition would generally be referred to as Duchenne muscular dystrophy (DMD).

Other neuromuscular pioneers, though, had written about the disease or one strikingly similar to it prior to Duchenne. They included Scottish surgeon Charles Bell, born in 1774, who was noted for identifying the facial paralysis Bell's palsy and also for distinguishing between sensory and motor nerves.

English physician Edward Meryon, born circa 1807, also wrote about DMD in great detail, taking pains to conduct post-mortem microscopic examinations of muscle tissue of affected boys. He observed the utter destruction of muscle fibers as well as the breakdown of the surrounding muscle sheath, a feature that Duchenne would fail to note.

Nonetheless, Duchenne's description in 1868 was the fullest and most accurate to date. Duchenne was also notable for placing an emphasis upon the importance of studying the disease in living subjects.

SEASIDE DOCTOR

Born in 1806 in the French seaside town of Boulogne, Duchenne was the son of a line of seafarers. Although he turned his back on family tradition when he chose to become a doctor, there's a definite touch of the maritime in one of his unique contributions to neuromuscular science.

Duchenne fashioned a "harpoon," a small hollowed-out instrument used to penetrate the skin of living subjects and extract samples of muscle tissue for examination. He used the technique -- the forerunner of today's muscle biopsy -- to examine muscle tissues of the same patients at various ages.

Duchenne, a quiet, introspective young man, had begun his medical practice in Boulogne treating fishermen and their families. Then Duchenne's wife died shortly after giving birth to their son; the wife's family blamed Duchenne for her death.

Prone to depression and acting perhaps from an unfounded sense of guilt, Duchenne agreed to let his mother-in-law take over his son's upbringing. As a result, Duchenne would remain estranged from his son for many years.

Although only in his 20s, Duchenne nearly gave in to melancholy at this point. He neglected his patients and virtually abandoned his practice.

But he was revitalized by an odd fascination: his growing interest in the ability of electricity, when applied to a patient's skin, to cause muscles to contract. He resumed his medical practice. Then, at age 36, he moved to Paris. Lacking a formal appointment, he visited hospital wards across the city, seeking out intriguing cases of nerve and muscle disorders.

THE MAN WITH THE BOX

Duchenne continued his use of "faradism," the application of electricity to the skin for diagnostic or therapeutic purposes. He built his own electrical box-like machine and carried it with him on rounds to stimulate the nerves and muscles of patients. This was important in that it allowed him to map the muscles of the body and note their functions.

The eccentric and somewhat socially awkward doctor from the provinces was initially held up for ridicule by some Paris colleagues. Eventually, though, recognition began to reward Duchenne's pursuits. He received a prize for his work mapping the muscles of the face; the "Duchenne smile" referred to his observation that genuine smiles showing real happiness and delight utilize not only the muscles of the mouth but also those of the eyes.

SIGNS AND SYMPTOMS

In 1858, Duchenne documented the case of a 9-year-old boy who was losing the ability to walk due to a muscle-wasting disease. Duchenne sought out additional cases. In 1868, he published an extensive account of DMD based on observations of 13 different cases, listing the disorder's signs and symptoms and even noting the possibility that intellectual impairment might be a facet of the disease.

Duchenne's painstaking observations in the Paris hospitals helped identify other conditions in addition to DMD, including adult spinal muscular atrophy (Aran-Duchenne type), facioscapulohumeral muscular dystrophy (also credited to Landouzy and Dejerine) and locomotor ataxia, an unrelated disorder caused by syphilis.

By observing the history of DMD's presence in families, it was possible for Duchenne and other pioneers to correctly deduce that the disorder was inherited, affecting males predominantly.

DISEASE ORIGIN

It wasn't so easy, however, to figure out the general cause of the disease. Was its origin in the muscle tissue itself or in the nerves? Duchenne held to the view, now known to be incorrect, that the nervous system played an inciting role.

Duchenne may have been swayed by the prevailing wisdom as represented by his friend and Paris' most acclaimed neurologist of the time, Jean-Martin Charcot. A world-famous teacher whose lectures on hypnotism and hysteria were an inspiration to young Sigmund Freud, Charcot attributed nervous system involvement to all muscle-wasting diseases.

Others, though, including German physician Ernst Leyden, would begin to turn the tide away from this type of thinking by suggesting that DMD and other inherited forms of muscular dystrophy should be placed in a category separate from muscle-wasting diseases that were known to be caused by nerve damage.

DUCHENNE'S SUCCESSORS

More diseases such as Charcot-Marie-Tooth disease, Werdnig-Hoffmann disease (a form of SMA) and myasthenia gravis were identified as the century drew to a close; the need for a reliable system of classification became more pronounced.

German professor Wilhelm Erb, one of the discoverers of myasthenia gravis, was the first to make a major attempt to differentiate between what he dubbed the various forms of dystrophia muscularis progressiva, classifying them by age of onset.

Erb theorized that DMD was caused by improper nutrition. The theory, mistaken though it was, at least provided a metaphorical glimmer of the real underlying cause of DMD: the degradation of muscle cells due to lack of a needed protein.

In 1879, English neurologist William Gowers wrote about a leg-grasping maneuver used by boys with DMD while attempting to stand. Also noted by Duchenne, this recognizable manifestation of DMD is remembered as Gowers' sign.

Gowers, who added greatly to clinical understanding of DMD, wrote feelingly of the disorder, saying: "The disease is one of the most interesting and at the same time most sad of all those with which we have to deal: interesting on account of its peculiar features and mysterious nature; sad on account of our powerlessness to influence its course."

MODERN DEVELOPMENTS

Other pioneers carried forward investigation of DMD in the 20th century. In America, ground-breaking studies by Ade T. Milhorat and H.G. Wolff focusing on creatine blood levels opened the door to new diagnostic technology and a more sophisticated understanding of the cellular processes underlying DMD.

The 1950s signaled tumultuous developments, including the founding of the Muscular Dystrophy Association and the establishment of a reliable classification of the various disorders in the muscular dystrophy family. This classification was augmented in 1957 by P.E. Becker's description of the less severe variant of DMD that now bears his name.

Subsequent decades brought a rush of advances in recombinant DNA technology leading to the discovery in 1986 of the gene that, when defective, causes Duchenne and Becker. The identification of the protein missing or diminished in the muscle cells of affected boys, dystrophin, followed quickly in 1987.

At last there were treatment possibilities for DMD, such as the drug predni-sone and current efforts to launch human trials in gene therapy.

A LEGACY OF HOPE

Although never as famous as his friend Charcot, Guillaume Duchenne earned a measure of fame and respect in his later years. But those same years were also touched by sadness and profound depression, due to the death of Duchenne's son, who had eventually become close to his father and followed in his footsteps as a doctor.

Charcot, who recognized Duchenne's importance, stayed at his friend's bedside when Duchenne lay dying of a cerebral hemorrhage in 1875.

The Lancet eulogized Duchenne thus: "His reputation has come out clear and bright as an honest, hard-working, acute and ingenious observer, an original discoverer, a skillful professional man and a kind-hearted, benevolent gentleman."

If, like Gowers and others, Duchenne was dismayed by the seemingly unstoppable nature of DMD, he never let it deter him from making his rounds from one end of Paris to the other, recording minute observations and dreaming up harpoons and strange electrical boxes.

Perhaps Duchenne, despite his melancholy nature, never doubted that the devastating illness he so tellingly described would ultimately be conquered and itself become a part of medical history.