There have been days -- many days -- when Dr. Jeffrey Rothstein has been forced to tell three, even four patients that they had a disease that would paralyze virtually every muscle before it killed them. So when Jenifer Estess, a young theater producer from New York, walked into his office at the Johns Hopkins School of Medicine with all the classic symptoms, he eased into a speech he had given hundreds of times.
Rothstein explained that she was losing the nerve cells that power her muscles. This accounted for the gnawing fatigue that was turning her feet to lead and the odd twitches rippling along her arms and legs. As the disease progressed, she would lose the ability to walk and talk, to lift a hand, even to breathe.
There was little she could do. She could take a medication that might slow her decline. She could enroll in drug trials that might help doctors to find new treatments. And she could enjoy the good days that remain.
Like most of Rothstein's patients, Estess was devastated to hear that she would die one of nature's cruelest deaths. But she was also furious -- and furious at him.
Wasn't there a better drug? asked Jenifer, who had made the trip with her mother and three sisters. Doctors could replace diseased hearts, why not nerve cells?
Crammed inside Rothstein's office, the family peppered him with questions, stretching a one-hour appointment to four.
"The whole thing seemed kind of absurd, like he was in the dark ages," says Estess, an imposing woman with straight, raven-black hair. "Didn't he have anything to offer me? What was going to happen to my romantic life? What was going to happen to my work life?"
Nothing about that visit four years ago suggested that this unlikely pair would become partners in a campaign to reverse a degenerative disease that has long been regarded as incurable.
Estess and her sisters would raise the money, recruit the scientists and provide the emotional fire. "They are the ones who are running the show," Rothstein said. "They are the ones providing the engine to run everything."
Rothstein would direct the science, a controversial effort to harness primitive stem cells -- precursors to every specialized cell in the human body -- to regenerate dying tissues.
"It's the worst thing that can happen to you," Jenifer says of her disease. "But Jeff was the perfect person to turn it around. Now, he's a leader in getting the puzzle solved."
Today, President Bush is wrestling with the question of whether to allow federal funding for stem cell research. Because the cells are derived from fetuses and embryos, opponents say, a federal role would involve the government in the destruction of life in its earliest form.
Advocates, of course, see it differently. Rothstein and the Estess sisters, who have relied on private money, argue that federal sponsorship would get more scientists involved and speed progress toward lifesaving treatments.
Who might benefit is hard to predict. Perhaps, say advocates, the work will bring treatments for Lou Gehrig's disease, the affliction that stalks Jenifer Estess. Perhaps, they say, it will help people with Alzheimer's, Parkinson's, diabetes and spinal cord injuries.
Brimming with optimism, Rothstein admits that his enthusiasm may have produced unrealistic expectations that a cure is close at hand.
"I can't say it's going to happen next year or the year after," he said. "But I'm convinced we're going to get real therapies. I believe in the biology."
An angry patient
Jenifer's odyssey started in 1996 with a strange pop in the back of her arm. She had just finished working out in a Manhattan gymnasium when a muscle twitched, setting off a spasm that quickly passed.
"I thought it was from working out too much in the gym," she says. "You know how you do those inverted pushups? The back of my arm would just be moving, twitching."
But the twitches continued, and at times it looked as if every fiber along her arms and legs was jumping and rippling at random.
Her internist said the problem was in her head; a neurologist said she was fine. But Estess became alarmed when her gait became sluggish and she struggled to climb the stairs of a Broadway theater. Finally, early in 1997, a neurologist at Columbia University would diagnose her problem as Lou Gehrig's disease. She was only 35.
Known technically as amyotrophic lateral sclerosis, the affliction destroys the body's store of motor neurons -- cells of the brain and spinal cord that signal muscles to move.
Lifting a hand or turning one's head becomes impossible. Eventually, so does swallowing and breathing. Once diagnosed, the average patient lives two to five years.
Though she was clearly failing, Estess hardly felt like someone with a terminal disease. She convinced herself that another doctor, perhaps the foremost expert in the world, might find a completely benign reason for her symptoms.
So on a blustery spring day in 1997, Jenifer boarded a train with her mother and three sisters.