Myasthenia gravis is almost sublime in its simplicity, at least in the context of autoimmune disorders.
Those with the disease produce antibodies which, acting as a nerve impulse's worst nightmare, attack acetylcholine receptors at neuromuscular junctions. Since these receptors are in essence the conduit for the nerve impulse, myasthenia gravis, left untreated, causes double vision, weakness and fatigue in muscles and joints, and, in severe cases, sufferers may be unable to swallow, move their arms and legs or breathe on their own.
Fortunately for those afflicted with myasthenia, today it is a very treatable disorder because it is considered the most thoroughly understood of all autoimmune diseases. Ask 20 medical students about the disease on an exam, and you're likely to get 20 correct responses.
Both myasthenia patients and med students have Daniel Drachman to thank.
Drachman, a professor of neurology and neuroscience at the School of Medicine, has been a seminal figure in the history of myasthenia gravis. For nearly 40 years he has worked to unravel the mysterious mechanisms underlying this disease and, in doing so, has spurred the advancement of treatments that have drastically improved the quality of life for patients and reduced the mortality associated with this disease.
Drachman is certainly no one-hit wonder, however. His basic and clinical research have advanced the understanding of other neuromuscular diseases as well, bringing forth new therapies to improve treatment for patients with disorders ranging from muscular dystrophies to motor neuron disease. Among his historical accomplishments are interpreting the mechanism behind arthrogryposis and explaining the critical role of neuromuscular transmission in muscle trophism. He also has more than 200 scientific publications to his credit and has trained over 50 clinical scientists and basic researchers.
On June 16, the Department of Neurology celebrated its 2000 Kroc Neuroscience Symposium in his honor. The full-day event drew renowned neurologists, many of whom had studied under Drachman, from around the world to pay a fitting tribute to this swami of the synapse who is stepping down as director of the Neuromuscular Program he began 30 years ago.
In his symposium introduction, John Griffin, professor and director of Neurology, pointed to a list on the blackboard behind him containing the names of those currently associated with the Neuromuscular Program.
"I would submit that this is certainly the largest and probably the finest neuromuscular group that has ever been assembled," Griffin said. "They are collectively Dan's kids."
Griffin also used his opening to offer reassurances that Drachman is neither retiring nor slowing down but is, in fact, "more active then ever."
Evidence of this is Drachman's continued dogged pursuit of more effective therapies and a cure for myasthenia gravis.
In the "bad old days," as Drachman describes them, 20 to 30 percent of people inflicted with myasthenia would die. Today, the promise of gene therapy, the study of which Drachman is intimately involved in, has the implication of effectively treating the disease without the side effects typically caused by immunosuppression, which is currently the most effective treatment for myasthenia.
"Gene therapy will target the specific abnormal immune response and leave everything else alone," Drachman says with the enthusiasm of a first-year resident. "It will act like a guided missile."
Drachman came to Hopkins in 1969 with five other new faculty, and under the leadership of Guy McKhann started the Department of Neurology. Drachman then and now views Hopkins as a "very fertile place" and says the opportunity to be part of a department's inception was a dream come true.
A graduate, along with his twin brother David, of New York University College of Medicine, Drachman can trace his interest in neuromuscular diseases to his days as a resident at the Boston City Hospital. He recalls a child he came across who was diagnosed with arthrogryposis multiplex congenita--commonly known as clubbed joints--and who subsequently died.
Drachman figured out that the child's condition likely was a result of a viral infection the mother had sustained during her pregnancy that paralyzed the fetus. Any event that could paralyze the fetus prior to birth, he concluded, would result in the failure of joint development. He spent the next three years at the National Institutes of Health testing his hypothesis. One of his tests involved injecting a paralyzing agent into chicken embryos inside an egg.
"I realized when I did that, not only were the joints abnormal but the muscles atrophied," Drachman says. "I said, 'Aha, this has to tell us that the transmission from nerve to muscle plays a role in maintaining muscle bulk, not just the movement of the muscle.' "
This discovery eventually led him in 1972, alongside Douglas Fambrough, now a professor of biology in the School of Arts and Sciences, to first describe the receptor effect in myasthenia gravis.
Neurology director Griffin describes this momentous discovery as propelling the "golden decade of research" for neurology. "He changed the thinking about this disease," Griffin says. "It was a stunning breakthrough for autoimmune diseases in general."
Drachman says he owes it all to his persistence. "Basically I followed my nose from one area of research to another," Drachman says. "What you can conclude is that what really happens in research is, the more you find out, the more questions there are."
You can also conclude, in Drachman's case, the egg came before the chicken.
Andrea Corse, assistant professor of neurology and a former fellow of Drachman, says Drachman is the embodiment of the "Hopkins triple threat," being equally adept at research, clinical care and teaching.
"He is not just a pure scientist," Corse says. "He teaches by example and makes himself very accessible to his patients. If they need him, they can reach him in his office very late into the night. He is also proficient at taking what he learns in the lab and in the clinic and then turning that into effective therapies for his patients."
Corse, who coordinated the symposium, said the event was not just a celebration of Drachman's medical work but "a tribute to him as a person."
When Drachman is not in the classroom, lab or clinic, you might find this Renaissance man bicycling up a mountain trail, fly fishing in a stream somewhere or diligently practicing his clarinet, an instrument he first picked up when he was 13 years old. His love of fishing is quite apparent from the mounted tarpon and picture of a salmon run in Alaska hanging on his office wall.
"I try to go fishing once a year somewhere interesting," Drachman says, mentioning his plans to go trout fishing in Montana later this year. "The thing about fishing is that it drags you to beautiful places."
Drachman was able to visit many "beautiful places" in 1990, when he and his wife, Jephta, director of the Shriver Hall Concert Series, traveled cross-country on bike to Seattle to visit one of their three sons. The two trained for months for a trip that would eventually take three months to complete.
Drachman says it was a "once in lifetime experience" that allowed him to explore middle America.
"I see patients from all over, but here, I am dressed in my white coat, seated behind my desk; there, I was simply a biker," Drachman says. "I saw it all from a different perspective. What a wonderful trip that was."
Drachman says he almost didn't take the trip because he was reluctant to take months off from his work and his patients. "Then Jephta told me, if I don't do it now, the next wheeled vehicle I'll be going in will be a wheelchair," Drachman says with a smile.
Asked what keeps him going, Drachman says it has a lot to do with a New York Times article about one of his medical discoveries, which ran several years ago. A classroom of fifth-graders, he said, apparently was told to write to someone "famous," and one student wrote a letter to him about his recent discovery.
"The student's parting citation was, 'Keep up the good work in helping to cure deadly diseases,' " Drachman says. "That is why I do it."