dopamine—an important neurotransmitter—than a normal brain. The basal ganglia are wired into circuits that run all over the brain; they affect a wide range of behaviors: motor control, higher-level thinking, and eye movement, as well as impulse control and enthusiasm.
“People with Lesch-Nyhan have an excess number of involuntary movements,” Jinnah said. “It’s as if they are stepping on the gas too hard when they try to do something. If you ask them to look at a red ball, for instance, their eyes go to everything except the red ball, and they can’t explain why. Then, if you introduce a yellow ball into their field of view but you don’t say anything about it, they watch the yellow ball.” The moment you draw their attention to it, however, they look away. Most Lesch-Nyhan people can’t read, and even watching television may be difficult or impossible for them—their eyes refuse to follow the action on the television screen.
“Lesch-Nyhan is at the far end of a spectrum of self-injurious behavior,” Jinnah went on. “You and I and everyone who is human, we all do things that are bad for us. We’ll sit down in front of the television and eat a quart of ice cream. We all have self-injurious impulses, too. Driving a car, we can have a strange impulse to drive it the wrong way and smash it into something.” People who are afraid of heights can experience the sensation that they may throw themselves from a high place, driven by some impulse they can’t control. Edgar Allan Poe called such promptings “the imp of the perverse.” The imp may be signals coming out of the basal ganglia of the brain. “Many people bite their fingernails,” Jinnah said. “They’ll tell you it’s gross and that they don’t want to do it—‘Sometimes I get nervous and start biting my fingernails,’ they’ll say. There are people who chew their lips nervously. Now let’s turn up the volume a little: some people bite their cuticles. Turn up the volume a little more: some people bite their cuticles until they bleed. Now let’s turn the volume
We can all think of things we’ve done to ourselves that make us cringe. It’s the inexplicable choice that brings about the very thing we feared the most. A shadow of self-sabotage seems to move behind the scenes on the stage of history. Napoleon’s invasion of Russia comes to mind. The mass behavior of much of the German population before and during the Second World War has a Lesch-Nyhanish quality. Israelis and Palestinians fight, neither side seeming able to compromise sufficiently to truly benefit their self-interest; Palestinian factions fight one another, like the hand attacking the face. Wars are about power, control of resources, and unrighted wrongs, to be sure, but they also seem to reveal a glimpse of self-mutilation in the human species. Perhaps there is a little bit of Lesch- Nyhan in each of us.
In a medical sense, Lesch-Nyhan looks like Parkinson’s disease reversed. People with Parkinson’s have trouble starting physical actions. Lesch-Nyhan people start actions too easily and can’t stop an action once it starts. Because Parkinson’s is also associated with a deficiency in the dopamine of the basal ganglia, scientists have looked to each disease for clues to the other.
In 1973, a researcher named George Breese, at the University of North Carolina School of Medicine, was working with rats that modeled Parkinson’s disease. He was treating newborn rats with compounds that changed the dopamine levels in their brains when, to his surprise, the rats started chewing off their paws. He had inadvertently created a Lesch-Nyhan rat. He was absolutely horrified, yet felt he might be tantalizingly close to a cure for Lesch-Nyhan. “I’ll not go further into the details of what the rats were doing. They weren’t biting their mouth tissues the way human patients do,” Breese told me. If he gave the self-injuring rats another compound, they stopped biting their paws—that is, he found a way to reverse the symptoms. “We treated the rat the moment we saw the animal make the first pinprick injury to its paws,” he said. The compound, however, has never been approved for use on humans.
IN APRIL 2000, Takaomi Taira, a neurosurgeon at the Tokyo Women’s Medical University, performed brain surgery on a nineteen-year-old man with Lesch-Nyhan. The young man was living with his parents in a district north of Tokyo. In addition to exhibiting self-injurious behavior, he had the spastic, stiff, thrashing movements of dystonia. “These dystonic movements were getting more severe almost by the day, and his parents were getting desperate,” Taira said to me recently. He decided to perform a procedure called deep-brain stimulation to try to calm down these movements.
Deep-brain stimulation was developed by doctors more than twenty years ago for treating people with Parkinson’s disease. One or more thin wires are carefully navigated through the brain until they stop in a part of the basal ganglia called the globus pallidus (the “pale globe”). The wires are connected to a battery pack, which is implanted under the skin of the patient’s chest, and a faint, pulsed current of electricity runs through them into the globus pallidus, numbing a spot the size of a pea. The patient feels nothing. The procedure often helps calm the tremors in Parkinson’s patients’ hands and limbs, and helps them walk more easily.
“After the surgery, the boy’s dystonic movement completely disappeared,” Taira said. He sent him home with the deep-brain stimulator, feeling that the operation had helped. Several months later, the young man’s parents told Taira that he had stopped biting himself. He was still in a wheelchair, and his uric-acid levels remained high, but he was reading comic books and watching television, and seemed to be enjoying life as never before. “It was completely unexpected, remarkable, almost unbelievable,” Taira said. A few years later, the young man suddenly began biting his hands again, and the parents brought him back. “I checked the device and found that the battery was flat. I replaced the battery, and his symptoms were controlled again,” Taira said.
A group at the Research Group on Movement Disorders in Montpellier, France, led by a neurosurgeon, Philippe Coubes, has given deep-brain-stimulation implants to five Lesch-Nyhan patients. His method involves the insertion of four wires into the brain. “So far, we have three patients who are doing very well and two who are having an intermediate response—the response of one of those is not poor but is not as good as the others,” Coubes said. “I’m not sure we will be able to control all their behaviors over the long term, but we are in the process of getting a better understanding of deep-brain stimulation for these patients.” The imp of the perverse could be put to sleep, but nobody knew how to make it go away.
Scientists aren’t sure why deep-brain stimulation seems to work in some patients. Indeed, the results are a reminder of how obscure the workings of the brain still are. William Nyhan was cautious about the procedure’s potential. “I see these kids as fragile, and they don’t respond very well to surgical invasions,” he said.
At Johns Hopkins, though, Jinnah was anxious to begin a study on a group of Lesch-Nyhan patients using deep-brain stimulation. He still needed to get funding and to receive approval from the federal government. (The procedure has not been specifically approved for Lesch-Nyhan patients.)
Jinnah has never had an easy time getting funding and attention for Lesch-Nyhan research. “People ask me, ‘Why not study more common diseases?’ My answer is that if we neurologists did that we’d all be studying Alzheimer’s disease, Parkinson’s disease, and strokes. There are thousands of other brain diseases out there, and they’re all orphans. But these rare diseases may teach us something new about the brain, something relevant to the common brain diseases that affect so many people.”
I WENT BACK several times to visit James Elrod and Jim Murphy and began helping their staff with daily tasks. Elrod spat in my face a few times, and gave me a left jab to the jaw that made me see stars, for which he apologized afterward. Once, his Kevlar-covered fingers closed on my skin like pliers; he apologized while we both worked to get them loose. Murphy, at his thirty-first birthday party, planted his face in his birthday cake, then punched me in the groin so hard that I collapsed to the floor. Nevertheless, I came to like them a lot.
Murphy had a record of making trouble in shopping malls. Malls put him in a bad mood, especially around Christmastime. “Too many people around. They make me nervous,” he explained to me.
One time, his assistants took him to a mall to do some Christmas shopping. A man dressed as Santa Claus was sitting in a snow scene that day, with children lining up to meet him. Murphy told his assistants that he would like to have his picture taken with Santa (one of them had a camera). They didn’t see how they could refuse the client’s request. They parked Murphy’s wheelchair in the line of children, and Murphy cautioned the children to watch out for his arms and legs. (Neither Murphy nor Elrod had been known to lash out at a child.)
Murphy got to the head of the line. The Santa asked Murphy if he’d like to sit on his lap.
Murphy said yes. The assistants placed him on the Santa’s lap. The assistant with the camera, a young man named Dan Densley, got ready to take a picture.
“Ho, ho, ho! What do you want for Christmas?” Santa asked.
“A woman,” Murphy answered, and delivered a punch to Santa’s jaw. Santa’s beard seemed to explode, and his eyeglasses went flying. The assistants grabbed Murphy and rolled him out of the mall at a dead run.
