Not long after Christopher Reeve broke his neck in a 1995 equestrian accident and became paralyzed, the handsome actor who starred in Superman declared that he would walk by his 50th birthday.
Though Reeve won't reach that goal - he turns 50 next week and remains a quadriplegic - the world took notice when a doctor reported that Reeve had made startling progress in the three years since he started exercising on a stationary bicycle with the aid of electrical charges that triggered his muscles.
Reeve, says Dr. John W. McDonald of Washington University in St. Louis, can move his right wrist and some of his fingers and toes. He can feel a pin prick practically anywhere on his body. He can detect degrees of hot and cold. He can straighten his arms and legs when floating in water, and can spend up to an hour off his ventilator.
Such gains might seem modest to anyone who hasn't spent years in an electric wheelchair, braced to sit upright and dependent on others for care.
But to Reeve, his gains are far from trivial. Just recovering some ability to feel the hugs of family members has given him a stronger connection to the world around him.
"What is so important about sensation is contact with other people," Reeve says in remarks accompanying McDonald's report in Journal of Neurosurgery: Spine. "It makes a huge difference if someone touches you on the hand, and you can feel it."
To Reeve and doctors trying to cure paralysis, his case hints at the exciting possibility that a spinal cord that shut downs after a devastating injury can be coaxed back into action by hard, relentless exercise.
"What he's been able to achieve illustrates the promise and the limitations of such exercises," says Dr. Wise Young, a spinal injury researcher who heads the neuroscience department at Rutgers University.
"The promise is that, indeed, somebody as severely injured as he can get back some function. The limitation is that the function he has is not sufficient. Moving a finger or toe is not the same as walking or being able to use his body."
For years, patients have been told that any significant recovery usually occurs in the first six months after an injury and is usually complete in the first two years. But in the past decade, doctors have been intrigued by the idea that activity - rigorous exercise in a physical therapy setting - can cause nerves to regrow or form new connections.
In 1999, McDonald designed a program for Reeve. Three times a week, Reeve was placed on a stationary bicycle. Six wires streaming from a computer were connected to muscles on his legs and buttocks. Electrical current stimulated the muscles in a rhythmic sequence and set his legs in motion. The exercise continued for an hour a day.
Reeve's progress was charted on an index developed by the American Spinal Injury Association. Patients placed in category A have no sensation and those rating an E are considered normal. Over the course of three years, Reeve rose from A to C.
"There hasn't been a single reported case of someone who had substantial recovery sufficient to move him up two classifications more than two years out from an injury," McDonald said in an interview.
What actually happened in Reeve's injured spinal cord remains a mystery, but McDonald proposes three possibilities.
Reeve's injury broke the circuitry that sends messages up and down the cord. McDonald says it is likely that a slender connection survived but wasn't functioning, and was "retrained" to transmit some information.
Another possibility is that neurons on either side of the injury site reached out and connected with each other - in effect, bridging the injury. Or, perhaps, new cells might have grown in the area.
"We have no idea what role activity had in this," McDonald says. But he hopes to find answers by examining the spinal cords of paralyzed animals whose muscles were electrically stimulated.
To see if Reeve's gains were a fluke, McDonald is also comparing 20 paralyzed patients who were placed on heavy exercise with 20 others.
Dr. Peter Gorman, director of the spinal cord injury program at Baltimore's Kernan Hospital, says Reeve's progress is highly unusual, but the cause remains open to question. "There haven't been reports of such spontaneous recovery," he says. "The question is whether his neurologic recovery was directly caused by the intervention."
For scientists, there is always the possibility of another cause that hasn't been considered.
At the Veterans Affairs Hospital in Cleveland, Dr. Hunter Peckham has used electrical stimulation to help stroke patients open their hands and move other parts of their body more vigorously. The treatment seems to prod the injured brain into remembering how to instruct the body to do such things. Perhaps, in a similar way, Reeve's treatment has prodded the spinal cord into turning up the volume on signals that were flowing - albeit weakly - even after the injury.
Although Young shares the excitement about the potential of electrical stimulation, he notes that Reeve has been exercising for years on state-of-the-art equipment in his Bedford, N.Y., home gym. His routine has included treadmill exercises in which he was supported in a parachute-like harness while three attendants moved his legs.
And Young, who befriended Reeve shortly after the injury, says the actor started feeling some faint sensations a few years after he was paralyzed, so the recovery did not happen as suddenly or as belatedly as reports might suggest. It is possible that Reeve is now realizing the cumulative gains of many years of hard work.
Many doctors have noted that Reeve has probably exercised more and received better care than anyone else so severely injured. Even if exercise prompted his recovery, it cannot be assumed that the average patient could accomplish what he has.
Perhaps more important than Reeve's ability to wiggle some fingers and toes are the remarkable gains he has made in his overall health. Exercise is widely credited with reversing the osteoporosis that made his bones prone to fracture. He has suffered fewer bladder or lung infections and, since 1999, has not been hospitalized for a medical complication.
Exercise might also keep Reeve healthy enough to benefit from the new drugs or treatments such as stem cell and nerve transplants that are on the horizon. Young says he is optimistic that physical activity will become one of several weapons that will be combined to repair the injured spinal cord.
Young is also encouraged by research that shows the spinal cord needs only a small portion of its connections to function well; a paralysis victim might retain 5 percent, and just doubling the complement might be enough. And some experimental treatments have enabled lab animals with crushed spinal cords to walk again.
"If you said five or six years ago that the spinal cord can regenerate, people would say, 'I don't believe you,'" says Young. "Now, you can walk into an audience and say the spinal cord can regenerate, and you can see two-thirds of the audience nodding their heads."