Panic in Level 4

The Self-Cannibals

ONE DAY IN SEPTEMBER 1962, a woman who here will be called Deborah Morlen showed up at the pediatric emergency room of the Johns Hopkins Hospital, in Baltimore, carrying her four-and-a-half-year-old son, Matthew. He was spastic and couldn’t walk or sit up. As an infant, he had been diagnosed with cerebral palsy and developmental retardation. The hospital’s pediatric emergency room was in the Harriet Lane Home for Invalid Children, an old brick building that stood in the center of the Johns Hopkins complex. Deborah Morlen sat down on a wooden bench in the waiting room. Her son lay stretched across her lap. He couldn’t hold his head up, and his arms and legs thrashed around. His eyes were bright and restless. He was wearing mittens, though it was a hot day. Deborah Morlen had fastened the mittens tightly around his wrists with string, to keep them from falling off.

Eventually, a resident named Nancy Esterly saw Matthew in an examination booth, where she asked Deborah Morlen what was wrong.

Mattey was putting out strange-colored urine, Morlen told Esterly. “And there’s, like, sand in his diaper,” she said.

Nan Esterly removed the boy’s diaper. It was stained a deep, bright orange, with a pink tinge. She touched the cloth and felt grit. She had no idea what this was, except that the pink looked like blood.

She began asking questions of Deborah Morlen, getting the boy’s history. She eventually learned that Matthew had an older brother, Harold, who was also spastic and retarded, and also had had orange sand in his diapers. Harold was living at the Rosewood State Hospital, an institution for disabled children, outside Baltimore, while Matthew was living at home.

Since both brothers seemed to have the same condition, Nan Esterly thought it was likely that they had a genetic disease. A genetic disease is an inherited condition that runs in families, passing from parents to their offspring in their DNA. The human DNA, or human genome, is stored in the chromosomes, small elongated bodies in the nucleus of cells. Human cells contain two sets of twenty-three chromosomes (for a total of forty-six chromosomes in each human cell). The human genome contains a bit more than three billion letters of genetic code—enough letters to fill roughly a thousand complete editions of Edward Gibbon’s The Decline and Fall of the Roman Empire. A gene is a stretch of DNA that holds the recipe for making a protein or group of proteins in the body.

In 1962, not a whole lot was known about genes and the human DNA. Even so, by that time Johns Hopkins pediatricians had begun discovering many previously unrecognized genetic diseases. Some of the doctors, perhaps not very kindly, would occasionally refer to children with genetic diseases as FLKs, or funny-looking kids. The story around Johns Hopkins was that every time a kid with an unusual appearance showed up in the emergency room, a new genetic disease would be found. Nan Esterly noticed that Matthew Morlen was wearing mittens, even though it was a warm day. She admitted the little boy to the hospital.

ESTERLY TOOK a sample of the boy’s urine, and both she and an intern looked at it under a microscope. They saw that it was filled with crystals. They were beautiful—the crystals were clear as glass, and they looked like bundles of needles or like fireworks going off. They were sharp, and it was obvious that they were tearing up the boy’s urinary tract, causing bleeding. Esterly and the intern pored over photographs of various kinds of crystals in a medical textbook, trying to identify them by their shape. The intern asked if the crystals might be uric acid, a waste product excreted by the kidneys; however, cystine, an amino acid that can form kidney stones, seemed the more likely candidate. Esterly needed a confirmation of the diagnosis, so she carried the test tube upstairs to the top floor of the Harriet Lane Home, where William L. Nyhan, a pediatrician and research scientist, had a laboratory. “Bill Nyhan was the guru of metabolism,” Esterly told me.

Nyhan, who was then in his thirties, had built some equipment that he was using to identify amino acids. He had been identifying amino acids in cancer cells while trying to find ways to cure cancer in children. “It was one of my impossible projects in cancer research,” he told me. Nyhan later became a professor of pediatrics at the U.C. San Diego School of Medicine. “I love working with kids, but dealing with pediatric cancer was depressing, saddening, and, in truth, maddening,” he said. Nyhan ran some tests on Matthew’s urine, using the equipment he had designed. The crystals weren’t cystine or any sort of amino acid. They proved to be uric acid.

A high concentration of uric acid in a person’s blood can lead to gout, a painful disease in which crystals of uric acid grow in the joints and extremities, particularly in the big toe. Gout has been known since the time of Hippocrates, when ancient doctors recognized that it occurs mainly in older men. Yet the patient here was a little boy. Nyhan had a medical student named Michael Lesch working in his lab, and together they went downstairs to have a look at the boy with “gout.”

Matthew lay in a bed in an open ward on the second floor of the Harriet Lane Home. The ward was filled with beds, and most of them were occupied by sick children. Matthew was a spot of energy in the ward, a bright-eyed child with a body that seemed out of control. The staff had tied his arms and legs to the bed frame with strips of gauze, to keep him from thrashing, and they had wrapped his hands in many layers of gauze. They looked like white clubs. Nurses hovered around the boy. “He knew I was a doctor and he knew where he was. He was alert,” Nyhan recalled. Matthew greeted Nyhan and Lesch in a friendly way, but his speech was almost unintelligible: he had dysarthria, an inability to control the muscles that make speech. They noticed scarring and fresh cuts around his mouth.

They inspected Matthew’s feet. No sign of gout. Then the boy’s arms and legs were freed, and Lesch and Nyhan saw a complex pattern of stiff and involuntary movements, a condition called dystonia. Nyhan had the gauze unwrapped from the boy’s hands.

Matthew looked frightened. He asked Nyhan to stop, and then he began crying. When the last layer was removed, they saw that the tips of several of the boy’s fingers were missing. Matthew started screaming, and thrust his hands toward his mouth. With a sense of shock, Nyhan realized that the boy had bitten off parts of his fingers. He also seemed to have bitten off parts of his lips.

“The kid really blew my mind,” Nyhan said. “The minute I saw him, I knew that this was a syndrome, and that somehow all of these things we were seeing were related.”

Lesch and Nyhan began to make regular visits to the ward. Sometimes Matthew would reach out and snatch Nyhan’s eyeglasses and throw them across the room. He had a powerful throw, apparently perfectly controlled, and it seemed malicious. “Sorry! I’m sorry!” Matthew would call, as Nyhan went to fetch his glasses.

The doctors persuaded Deborah Morlen to bring her older son to the hospital. Harold, it turned out, had bitten his fingers even more severely than Matthew and had chewed off his lower lip down into his chin, at the limit of the reach of his upper teeth. Both boys were terrified of their hands and screamed for help even as they bit them. The Morlen brothers, the doctors found, had several times more uric acid in their blood than normal children do.

Nyhan and Lesch visited the Morlen home, a row house in a working-class neighborhood in East Baltimore, where Matthew had been living with his mother and grandmother. “He was a well-accepted member of his little household, and they were very casual about his condition,” Nyhan said. The women had devised a contraption to keep him from biting his hands, a padded broomstick that they placed across his shoulders, and they tied his arms to it like a scarecrow. The family called it “the stringlyjack.” Matthew often asked to wear it.

Nyhan and Lesch also discovered that they liked the Morlen brothers. Lesch, who became the chairman of the department of medicine at St. Luke’s–Roosevelt Hospital, in New York City, said, “Michael and Harold were really engaging kids. I really enjoyed being around them. I got beat up once by Matthew.” He had leaned over the boy and asked him how he was feeling, and Matthew had slugged him in the nose. Lesch had staggered backward holding his nose while Matthew said, “Sorry! I’m sorry!”

TWO YEARS AFTER meeting Matthew Morlen, Nyhan and Lesch published the first paper describing the disease, which came to be called the Lesch-Nyhan syndrome. Almost immediately, doctors began sending patients they suspected of having the disease to Nyhan. Very few doctors had ever seen a person with Lesch-Nyhan syndrome, and boys with the disease were, and are, frequently misdiagnosed as having cerebral palsy. (Girls virtually never get it.) Nyhan himself found a number of Lesch-Nyhan boys while visiting state institutions for developmentally disabled people. When I asked him how long it took him to diagnose a case, he said, “Seconds.” He went on, “You walk into a big room, and you’re looking at a sea of blank faces. All of a sudden you notice this kid staring at you. He’s highly aware of you. He relates readily to strangers. He’s usually off in a corner, where he’s the pet of the nurses. And you see the injuries around his lips.”

WILLIAM NYHAN was eighty-one, a tall, fit-looking man with sandy-gray hair and blue eyes. He ran marathons until he was about seventy, half marathons after that; he was now the top-seeded tennis champion in his age class in southern California. He had a laboratory overlooking a wild canyon near the U.C. San Diego Medical Center. One day when I visited him, the Santa Ana wind was blowing in from the desert, and the air had an edgy feel. Two red-tailed hawks were soaring over the canyon, tracing circles in the air. The distinct movements of the hawks revealed a pattern of flight engraved in the birds’ genetic code.

In the years since he had identified Lesch-Nyhan, William Nyhan had discovered or codiscovered a number of other inherited metabolic diseases, and he had developed effective treatments for some of them. He had figured out how to essentially cure a rare genetic disorder called multiple carboxylase deficiency, which could kill babies within hours of birth, by administering small doses of biotin, a B vitamin. Lesch-Nyhan, however, had proved to be more intractable.

Decades after the discovery of Lesch-Nyhan syndrome, it is still mysterious. It is perhaps the clearest example of a change in the human DNA that leads to a striking, comprehensive change in behavior. In 1971, William Nyhan coined the term “behavioral phenotype” to describe the nature of diseases like Lesch-Nyhan syndrome. A phenotype is an outward trait, or a collection of outward traits, that arises from a gene or genes—for example, brown eyes. Someone who has a behavioral phenotype shows a pattern of characteristic actions that can be linked to the genetic code. Lesch-Nyhan syndrome seems to be a window onto the deepest parts of the human mind, offering glimpses of the genetic code operating on thought and personality.

H. A. JINNAH, a neurologist at Johns Hopkins Hospital, has been studying Lesch-Nyhan syndrome for more than fifteen years. “This is a very horrible disease, and a very complex brain problem,” he said to me one day in his office. “It is also one of the best models we have for trying to trace the action of one gene on complex human behavior.”

A child born with Lesch-Nyhan syndrome seems normal at first, but by the age of three months has become a so-called floppy baby, and can’t hold up his head or sit up. His diapers may have orange sand in them, and his body begins a pattern of writhing. When the boy cuts his first teeth, he starts using them to bite himself, especially at night, and he screams in terror and pain during these bouts of self-mutilation. “I get calls in the middle of the night from parents, saying, ‘My kid’s chewing himself to bits, what do I do?’” Nyhan said. The boy ends up in a wheelchair, because he can’t learn to walk. As he grows older, his self-injurious behaviors become subtle and more elaborate, more devious. He seems to be possessed by a demon that forever seeks new ways to hurt him. He spits, strikes, and curses at people he likes the most—one way to tell if a Lesch-Nyhan patient doesn’t care for you is if he’s being very nice. (He wishes you would go away, so the Lesch-Nyhan part of him tries to keep you near him.) He eats foods he can’t stand; he vomits on himself; he says yes when he means no. This is self-sabotage.

A few hundred boys and men alive in the United States today have been diagnosed as having Lesch-Nyhan syndrome. “I think I know most of them,” Nyhan said. A boy known as J.J. whom Nyhan found in a state institution, where he’d been considered spastic and mentally retarded, ended up living in Nyhan’s research unit for a year. He was a lively, gregarious child whose hands seemed to hate him with a demonic precision. Over time, his fingers had gotten into his mouth and nose, and had broken out and removed the bones of his upper palate and parts of his sinuses, leaving a cavern in his face. He had also bitten off several fingers. J.J. seemed happy most of the time, except when he was injuring himself.

J.J. died in his late teens; in the past many Lesch-Nyhan patients died in childhood or their teens, often from kidney failure. (Both Morlen brothers died young.) Nowadays they may live into their thirties and forties, but they often die from infections like pneumonia. Occasionally, a man with the disease flings his head backward with such force that his neck is broken, and he dies almost instantly.

A Lesch-Nyhan person may be fine for hours or days, until suddenly his hands jump into his mouth with the suddeness of a cobra strike, and he cries for help. People with Lesch-Nyhan feel pain as acutely as anyone else does, and they are horrified by the idea of their fingers or lips being severed. They feel as if their hands and mouths don’t belong to them, and are under the control of something else. Some Lesch-Nyhan people have bitten off their tongues, and some have a record of self-enucleation—they have pulled out an eyeball or stabbed their eye with a sharp object such as a knife or a needle. (The eye is a soft target for the hand of a Lesch-Nyhan person.) When the Lesch-Nyhan demon is dozing, they enjoy being around people, they like being at the center of attention, and they make friends easily. “They really are great people, and I think that’s part of the disease, too,” Nyhan said. Some Lesch-Nyhan people are cognitively impaired and others are clearly bright, but their intelligence can’t be measured easily. “How do you measure someone’s intelligence if, when you put a book in front of him, he has an irresistable urge to tear out the pages?” Nyhan said.

IN 1967, J. EDWIN SEEGMILLER, a scientist at the National Institutes of Health, and two colleagues discovered that in Lesch-Nyhan patients a protein called hypoxanthine-guanine phosphoribosyl transferase, or HPRT, which is present in all normal cells, doesn’t seem to work. The enzyme is especially concentrated in deep areas of the brain, around the brain stem. The job of this enzyme is to help recycle DNA. Cells are constantly breaking DNA down into its four basic building blocks (represented by the letters A, T, C, and G, for adenine, thymine, cytosine, and guanine). This process produces compounds called purines, which can be used to form new code. When HPRT is absent or doesn’t work, purines build up in a person’s cells, where they are eventually broken down into uric acid, which saturates the blood and crystallizes in the urine.

In the early 1980s, two groups of researchers, one led by Douglas J. Jolly and Theodore Friedmann, decoded the sequence of letters in the human gene that contains the instructions for making HPRT. It includes 657 letters that code for the protein. Researchers also began sequencing this gene in people who had Lesch-Nyhan. Each had a mutation in the gene, but, remarkably, nearly everyone had a different one; there was no single mutation that caused Lesch-Nyhan. The mutations had apparently appeared spontaneously in each affected family. And in the majority of cases, the defect consisted of just one misspelling in the code. For example, an American boy known as D.G. had a single G replaced by an A—one out of over three billion letters of code in the human genome. As a result, he was tearing himself apart.

The HPRT gene is found on the X chromosome, which is the female sex chromosome and carries information that makes the person female. Women have two X chromosomes in each cell, and men have an XY pair. Lesch-Nyhan is an X-linked recessive disorder. This means that if a bad HPRT gene on one X chromosome is paired with a normal gene on the other X chromosome, the disease will not develop. A woman who has the Lesch-Nyhan mutation but carries it on only one of her X chromosomes doesn’t develop the syndrome. Any son she has, however, will have a 50 percent chance of inheriting the syndrome (if he gets the bad X chromosome, he will have the disease; if he gets the good one, he won’t), and any daughter will have a 50 percent chance of being a carrier. (Examples of this type of X-linked recessive disease include hemophilia and a form of red-green color blindness. Queen Victoria was a carrier of the hemophilia gene, but she didn’t have hemophilia. Some of her male descendents had it.)

Other genetic mutations have been associated with profound behavioral changes. Rett syndrome, which affects mostly girls, is caused by a mutation in a gene that codes for the MeCP2 protein. People with the syndrome compulsively wring their hands and rub them together as if they were washing them. Children with Williams syndrome have an elfin appearance, an affinity for music and language, an extreme sensitivity for sound, and are very sociable. Williams syndrome is caused by a deletion of a bit of code from chromosome 7.

There is still great uncertainty about how much of a role genes play in major, common conditions such as depression or bipolar disorder. One wonders where obsessive-compulsive disorders come from, or such behaviors as compulsive hand-washing, compulsive neatness. Do some people suffer from OCDs that are caused by misspellings in their code? What about borderline personality disorder? How many mental illnesses are the result of errors in the code or certain combinations of errors? No one knows. It seems quite evident that a lot of human behavior is affected or governed by the blueprint of a person’s DNA. Even where there is evidence of a family history of disease, scientists are unsure how a single gene could choreograph a suite of behaviors. There are roughly twenty-five thousand active genes in the human genome, each with about a thousand to fifteen hundred letters of code. The human genome could be thought of as a kind of piano with twenty-five thousand keys. In some cases, a few keys may be out of tune, which can cause the music to sound wrong. In other cases, if one key goes dead the music turns into a cacophony or the whole piano self-destructs.

The havoc that the Lesch-Nyhan mutation causes cannot easily be undone. Early on, Nyhan tried giving his Lesch-Nyhan patients allopurinol, a drug that inhibits the production of uric acid. The drug is effective with gout. It lowered the concentration of uric acid in Lesch-Nyhan patients, but it didn’t reduce their self-injurious actions. The uric acid, it seemed, was another symptom, not a cause of the behavior.

Nyhan experimented with simple treatments, such as soft restraints, which seemed to relax patients and made them feel safer from themselves. Matthew Morlen had frequently asked to be tied into his stringlyjack. Nyhan also began recommending that Lesch-Nyhan children have their upper teeth removed, so that they couldn’t bite off their lips and tongues as easily. “I’m profligate with those upper teeth,” he said. This led to arguments with dentists. Some dentists would refuse to extract healthy teeth, even when the Lesch-Nyhan syndrome was explained to them.

I was visiting Nyhan in his office, and there was a lull in the conversation. He sat back in his chair and looked at me. I couldn’t tell what he was thinking. Outside the window, the hawks were still riding thermals over the canyon. We had come to the end of knowledge about Lesch-Nyhan. The disease remained as mysterious and frightening as it had seemed on the day when Nyhan and Lesch had first seen it, nearly forty years earlier. But I had never seen it. “I can’t imagine what it’s like to have Lesch-Nyhan,” I finally said to him.

“You could ask someone who has it,” he replied.

I MET JAMES ELROD and Jim Murphy one winter day not long afterward. They were living next to each other in rented bungalows in a somewhat marginal neighborhood in Santa Cruz, California. James Elrod was then in his early forties, and Jim Murphy was just over thirty. They were close friends, except when their Lesch-Nyhan symptoms annoyed each other. (Murphy died in 2004; Elrod, who is fifty as I write this, became one of the oldest living people with Lesch-Nyhan.) The men were clients of Mainstream Support, a private company contracted by the state of California to help people with developmental disabilities live in community settings. Before he came to to Santa Cruz, James Elrod lived for eighteen years in a state institution in San Jose called the Agnews Developmental Center. Jim Murphy had spent all of his adult life in a California state institution in Sonoma. Mainstream employees, called direct-care staff, stayed with Elrod and Murphy around the clock, to help them with daily tasks and to make sure they didn’t harm themselves. Elrod and Murphy had the authority to hire and fire their assistants and direct their work, though an assistant could refuse an order if he thought it would put the client in danger.

At the time, Mainstream was run by two business partners, Andy Pereira and Steve Glenn. “James and Jimmy are real down and gritty guys,” Pereira said. “They are not sweet types. They’re into fast cars and women.” Steve Glenn confessed that he still had difficulty seeing into the labyrinth of Lesch-Nyhan. “There are these Lesch-Nyhan moments when you feel like you’ve kind of got it,” he said. “James and Jimmy are pretty good at telling you when they think they’re in danger of hurting themselves, but whenever they’re doing something, you always have to ask, Is this James or Jimmy, or is it Lesch-Nyhan?”

James Elrod had a square, good-looking face, which was marked with scars, and he had brown, hyperalert eyes. His shoulders and arms were large and powerful, but the rest of his body seemed slightly diminished. One day at the Agnews Developmental Center, before he was with Mainstream, an attendant left him alone at a dining table for a few minutes. To his horror, his left hand picked up a fork and used it to stab his nose and gouge it out, removing most of his nose and permanently mutilating his face. “My left side is my devil side,” he told me. When I met him, he wore black leather motorcycle gloves that had been reinforced with Kevlar. If he thought his left hand was threatening him or someone else, he would grab it or swat it with his right hand. He owned a pickup truck, and his assistants drove him around in it. He had a job working at a recycling facility. He also used to sell flowers on the Santa Cruz pier. He carried business cards explaining that he had a rare disease that compelled him to hurt himself. “I have injured myself in many ways including my nose, as you can see,” the card said. “I will even try to hurt myself by getting into trouble with others.” One day, a man bought some flowers from Elrod and said, “God bless you.” “Eat shit,” Elrod replied, and handed the man his business card. While crossing a street in his wheelchair, Elrod had been known to suddenly roll himself straight into oncoming traffic, yelling, “Slow down, you morons! Don’t you know it’s Lesch-Nyhan?” His assistants wrestled him to safety.

Elrod was sitting in front of his house in his wheelchair when I arrived. It was a sunny day. He offered me his right hand to shake. When I gripped his glove, the right index finger collapsed. “You broke my finger!” he gasped. Then he grinned and explained that he didn’t have that finger, as he had bitten it off some time ago.

I started laughing, but then regretted it. “I’m sorry to laugh,” I said, imagining what he had done to himself.

No worries. He had given me a test, and I had passed it: I had laughed. “A lot of people get uptight when I do that,” he said. “Kids love it. They want to break my finger again.” We chatted for a while. “Hey, Richard—danger,” he said.

“What’s wrong?”

He was staring at my notes. I had been taking notes, as usual, in a little notebook. He cautiously pointed his finger at the mechanical pencil I was using. “Hey, Richard. Your pencil is scaring me.” It had a sharp metal tip. “My hand could grab it and put it in my eye. Please step away from me and put your pencil down. Just listen.”

I backed away from him, putting my notes and pencil in my pocket. But then he said, “You’d better go see my neighbor. He’s waiting for you.”

It only occurred to me later that James Elrod might have entangled me in an act of self-sabotage. He had been looking forward to meeting a writer and describing his disease. He had been waiting in his driveway for me. Because he wanted very much to tell me about his disease, the Lesch-Nyhan part of him had threatened to grab my pencil and puncture his eye with it, had ordered me to put down my notes, and finally had sent me away to interview another man with Lesch-Nyhan syndrome, instead of himself. Was I reading too much into it? It was hard to say. It seemed as if he might be playing a chess game with himself in which he was doing everything he could to put his desires in checkmate.

JIM MURPHY was sitting in his wheelchair at a table in the living room of his house. He had been waiting for me, too. An assistant named Michael Roth was cutting up pancakes and feeding them to him with a spoon. Murphy was a bony man with dark hair and a lean, handsome face. He had a neatly trimmed goatee and a crew cut, and his eyes were mobile and sensitive-looking. His lips were missing. Two of his brothers had also had Lesch-Nyhan; they had died when they were young. “Jimmy will be shy when you first meet him,” one of his sisters told me on the phone. I could expect to hear a lot of swearing, though. “He doesn’t mean it,” she said. “When he swears at me, I just say, ‘I love you, too.’”

That day in Santa Cruz, Murphy stared at me out of the corners of his eyes, with his head involuntarily thrown back and turned away, braced against a headboard. His hands were stuffed into many pairs of white socks, and he wore soft, lace-up wrestler’s shoes. His chest heaved against a rubber strap that held him in place. He started throwing punches at me, and he kicked at me. He seemed to be enduring his disease like a man riding a wild horse. The wheelchair shook.

I kept back. “It’s nice to meet you,” I said.

“Fuck you. Nice to meet you.” Jim Murphy had a fuzzy but pleasant-sounding voice. His speech was very hard to understand. He looked at Michael Roth. “I’m nervous.”

“Do you want your restraints?” Roth asked.

“Yeah.”

Roth placed Murphy’s wrists in soft cuffs fastened with Velcro, and he placed his legs in cuffs, as well. The wheelchair trembled and rattled as his limbs fought against the cuffs.

“I’m a little nervous, too,” I said, sitting down on the couch.

“I don’t care. Good-bye.”

I stood up to leave.

Roth explained, however, that this was one of those Lesch-Nyhan situations where words mean their opposite.

I sat down again. “Do you want me to call you Jim or Jimmy?” I asked.

His answer was blurry.

“I’m having a little trouble understanding you,” I said.

“I duhcuh…”

“You don’t care?”

He repeated his words several times until he saw that I understood. He was saying: “I don’t care between Jim or Jimmy. Either’s fine.”

“I sort of like Jim better, myself.”

He said something I couldn’t understand.

“What’s that?”

He repeated his words. He was saying, “Do you want me to call you Richard or Dick?”

“Oh, I don’t care. Either is fine,” I said.

An impolite grin spread across Murphy’s face. “I’m going to call you Dickhead. That’s your new dickname.”

I burst out laughing.

Meanwhile Roth, the assistant, seemed not to be hearing a word of our conversation.

Later, Jim Murphy explained what his disease was like. “You try to tick everybody off, and then you feel bad when you do it,” he said. Slowly I became better able to identify his words. “If you get too close to me, I could—” He said something indecipherable.

“I’m sorry, what?”

“Coldcock you, Richard. I’ll say, ‘Get my water,’ and I’ll give you a sucker punch.”

A pair of red boxing gloves was hanging on the wall. Every day, his assistants placed him on a wrestling mat on the floor, where he rolled around and did stretches and then boxed with them. “I could definitely whip you,” he told me.

Later, Jim Murphy asked if I would like to go for a walk with him around Santa Cruz, alone, without his assistant. I said sure. Then he asked me to take off his restraints. “Don’t worry, Richard,” he said.

Feeling nervous about the situation, I opened his cuffs. His arms flew out and started waving around, but he didn’t throw any punches at me. I pushed him out the door. We went down a driveway and came to a cul-de-sac, where we had to make a decision, to turn either left or right.

“Go right,” he said. I started to turn him to the right “No! Left,” he said. So I turned left. “No! No! Right!”

We were trapped in a Lesch-Nyhan hall of mirrors, filled with reflections of desire and repulsion. “Which way do you really want to go, Jim?”

“Left.”

“Are you sure?”

“Left! Left!”

The leftward path led through a gate. As we passed through the gate, one of his sock-covered hands shot out and struck the gate, hard. He had compulsively hurt himself. I apologized to him and said, “I guess I really should have gone the other way.”

“Not your fault.”

I began pushing him along in the street, keeping away from mailboxes. (I was afraid he’d try to hit one.) I was beginning to be able to figure out his speech.

A young woman driving a vintage Ford Mustang convertible passed us.

He waved to her and called out a greeting, and she waved back; they apparently knew each other.

Murphy seemed entranced. “Did you see that? She waved at me. She’s beautiful,” he said in a slushy voice. “She likes me. I love Mustangs,” he added.

“I used to have a ’65 Ford Falcon when I was in college,” I said as I pushed him along. “It was a ’65 Mustang under the skin. It had the same engine and interior as the Mustang, but the body had this weird shape.”

“Yeah!” He grinned. “I love those old Falcons. Do you still have it?”

“I gave it to one of my brothers.”

“Does he like it?”

“Well, he sold it to some kid for fifty dollars.”

“Aw, no!” Murphy said. “I bet you want it right now.”

“I sure do.”

We ended up at a corner grocery store, and while Murphy chatted with a woman at the cash register, who was a friend of his, I went to the cooler case to buy him a Coke. “Get whatever you want. It’s my treat,” he said. “Take my wallet.” He used his eyes to indicate a pocket in the wheelchair where he kept his wallet.

“Thanks,” I said.

“Fuck you. You’re welcome.”

Later, at James Elrod’s house, I was sitting on his back porch and chatting with him, and he pointed out various plants he was cultivating in pots. The pots sat on shelves where he could reach them from his wheelchair. Elrod was a passionate gardener. He dug in the soil with his gloved hands; he didn’t dare hold a tool of any sort. His assistants often did gardening tasks for him, while he told them what to do.

“Jim gave me a new nickname,” I remarked to James Elrod.

“Yeah? What is it?”

“It’s ‘Dickhead,’” I said.

A glow of delight lit up Elrod’s face. “Hey, guess what. I’m going to call you…it’s…” He couldn’t get the word out. “Jack—” he mumbled.

“My name is Jack?” I asked.

“Eee! Aww!”

“What?”

“It’s Jackass, Dickhead!” He laughed uproariously.

JAMES ELROD was born in 1957 in a small town in northern California, where his father worked as a laborer in a rice-drying warehouse. As a child, he was never able to walk, and doctors diagnosed him with “cerebral palsy.” He had an older brother, Robert, who also had “cerebral palsy,” but, unlike James, Robert was considered to be mentally retarded. (Robert Elrod died in 1998.) James attended regular elementary school until he was in fifth grade, when his parents put him in a special education program.

“I couldn’t walk, but I could scoot,” James explained. Scooting meant crab-walking on his hands and feet with his stomach facing up and his rear end bumping along the ground. James and his older sister, who here will be called Marjorie, were very close as children. When they were children, Marjorie was James’s steadfast companion. She pulled James around in a wagon. Marjorie towed James to school every morning in the wagon, and she towed him home in the afternoon. James and his sister have remained close.

Their father drank heavily. He would come home drunk and become enraged with James. “My dad used to hit me with a belt on my bare back,” he said. “I’ll forgive him for it. But he never forgave me for being what I am.”

The family went camping in the Sierra Nevada, and James fished with his father and helped him hunt deer; he learned how to dress a deer. He hauled wood for the campfire, scooting around on the ground while balancing pieces of wood on his stomach. He was well-liked pretty much wherever he went.

His grandparents lived nearby in the same town, in a farmhouse near the railroad tracks. James was fond of his grandparents and spent much of his free time visiting with them. He liked to work in his grandmother’s garden with her, scooting up and down the rows of tomatoes, pulling weeds and helping out. Hoboes drifted by on the railroad tracks, walking along the back side of James’s grandparents’ property. James’s grandmother would hire the hoboes to pull weeds, and her payment was a sandwich. James pulled weeds along with the hoboes. He also delivered milk and cookies to the hoboes, perched on his stomach, and he hung out by the railroad tracks for hours, talking with the hoboes. Eventually, James’s grandmother invited a drifter named Herbie to come stay with the family and work for them, in exchange for room and board. For the rest of his life, Herbie made his home in a gardening shed behind James’s grandparents’ house.

Things were not so smooth at home, where his father became increasingly violent. “My father was drinking a lot,” James recalled. “He forced booze down my throat and then he lunged at my mother.” This terrified and enraged the boy, but he was helpless, and all he could do was scuttle around on the floor; he couldn’t protect his mother from the violence. Until then, he had not been known to engage in self-injury. “The first Lesch-Nyhan episode I remember was when I was about ten,” he said. “My mother was taking me home from school in the wagon and I jumped out the wagon and tried to hurt myself. Afterward, the school nurse called up Child Protection Services and told them that I was getting hurt a lot when I was around my mother.” These official suspicions of his mother tormented him as a child, because he knew very well that she wasn’t hurting him, he was hurting himself.

He went to high school, attending special ed classes, but as a teenager he became harder for his parents to manage. They eventually made him a ward of the state of California and had him put in a rest home for elderly people, hoping that he would receive good care there. The staff of the nursing home began giving him medication. He was a young man, full of energy, who ended up on sedatives in a room with Alzheimer’s patients. “There was only one other young person in the rest home besides me, and she was a sixteen-year-old girl,” Elrod said. “The worst part of it was they wouldn’t let me do any gardening.” This seemed to disturb the demon, and one day he threw himself through a glass window, cutting himself badly. His parents had him transferred to a nursing home in Sacramento. There he was allowed to have a garden, and he gave the products of his garden to the residents of the home—they got vegetables to eat and flowers to brighten their rooms. “The garden had really good soil,” he said. “I planted all kinds of bulbs there. I had tomatoes, cucumbers, squash, and beans growing in it, and good, big pumpkins. It had these really big sunflowers growing in a row.”

His sister, Marjorie, visited him there and discovered that the staff was giving him heavy doses of drugs—overmedicating him, in her view. “I raised Cain every time I went to see him there,” Marjorie said to me. “The staff said they were just doing what they had to do. They told me that I needed to have an appointment before I could see him. I told them I was going to come see my brother whenever I wanted. That was when James starting smashing his face on the table.” The nursing home couldn’t handle him.

At twenty-one, Elrod ended up at the Agnews Developmental Center in San Jose. Gardening was out of the question at the state institution. Elrod ended up being paired with a roommate who was profoundly retarded and couldn’t speak, though he made continual noise. “My roommate was a screamer, twenty-four/seven,” he said.

“It was just horrible for him,” Marjorie said.

In the state institution, his hands began to go out of control. They began attacking his face. He bit his hands in order to protect his face from attacks by them—he needed to hurt his hands in order to scare them away. He began to realize that his hands would stop at nothing if they got a chance. It was in the state institution one day when his left hand hacked off his nose with a fork. The Lesch-Nyhan demon came brilliantly awake, and turned its gaze on Elrod with murderous intent.

THERE HAVE BEEN about twenty autopsies of Lesch-Nyhan patients over the years. Their brains appeared to be perfectly normal. “It’s a problem in the connections, in the way the brain functions,” H. A. Jinnah, the Johns Hopkins neurologist, said. He had gotten interested in Lesch-Nyhan as a scientific enigma, but he quickly found that families all over the United States were sending Lesch-Nyhan patients to him, hoping for help. He couldn’t turn them away, and he had ended up looking after a large number of boys and young men with Lesch-Nyhan who were his patients. “It’s an orphan disease,” he explained. “Almost nobody studies it.”

During some of the autopsies, doctors had tested samples of brain tissue to see if they contained a normal balance of neurotransmitters—chemicals that are used for signaling between nerve cells. In the Lesch-Nyhan brains, a lemon-sized area containing structures called the basal ganglia, near the center of the brain, had 80 percent less 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 way up. Now you have someone biting off tissue and bone in his fingers, biting off the whole finger, and chewing his lips off. Where, in this spectrum of behavior, is free will?”

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.

JIM MURPHY had a passion for off-road driving, which he was not usually able to indulge. One day, I showed up in Santa Cruz in a rented Ford Expedition with four-wheel drive. A woman named Tracye Overby came along as Murphy’s assistant, while another assistant, Christopher Reeves, accompanied Elrod. Into the back of the vehicle we put a cooler holding a roast chicken and beer, and I drove the group to a dried-out lake bed near Watsonville called College Lake, which we’d heard was a good place for four-wheeling. On the way, I stopped to get directions from a California state trooper. “I would not advise going there with disabled people,” he said.

College Lake turned out to be a mile-wide expanse of clay covered with sand. The lake bed had a dark, wet-looking center and was surrounded by thickets of willows. I edged the Expedition out onto the sand, while Murphy and Elrod began to egg me on from the backseat. “Go faster,” Murphy said. “You’re driving like an old lady.” I gunned the engine, the Expedition leaped forward, and we raced across the sand. When I turned sharply, the men shouted with delight. I started cutting cookies and performed a figure eight, then aimed the vehicle toward the center of the lake and floored the accelerator. With the engine roaring, we passed the sunken carcass of a truck, buried up to its roof in clay. The Expedition began slowing down, even though the engine was running at full power. Then the vehicle began tipping over—which was when I realized that we were driving across quicksand. If we stopped, we would go down. I floored it again and turned back for the shore, but it was too late. We slowed to a halt with the engine making an extreme wailing sound and the wheels spinning. The Expedition settled down until its axles were buried; then the engine suddenly died. There was a moment of complete silence. Then the men erupted with profanities. “Jackass!” Elrod yelled.

The two helpers seemed unperturbed. “This is just the nature of our work,” Chris Reeves said. “Everything that you plan never goes as you planned it.”

I opened the door and tested my weight on the sand. At least the Expedition seemed to be floating on it. I got out my cell phone and started calling local towing services.

Elrod leaned over me. “Tell them you’ve got two Lesch-Nyhan guys in the car, and we’re going to cut your head off.”

After a number of calls, it became clear that the local towing companies wouldn’t touch College Lake. “I’ll just have to get somebody to tow me out,” one man said.

“We could call my lawyer,” Elrod suggested.

“Forget it!” Jim Murphy said. “Your lawyer won’t do us any good. Call the fire department. Help! Fire! Fire!”

I tried an outfit called Speed of Light Towing. A young guy answered the phone and said he couldn’t do it.

I told him it was a desperate situation. “I’ve got two disabled guys with me. They’re in wheelchairs and can’t walk. We’re in the middle of the lake,” I said.

“What?” he said. He needed to hear that again. “All right. I’ll try,” he finally said. I would have to pay him when he arrived, no results guaranteed.

“I’m nervous,” Murphy said. Blood dribbled out of his mouth—he was biting himself. Tracye Overby lifted him out of the car, carried him across the sand to the shade of some willows, and sat down, holding him in her lap. She wiped the blood from his mouth with a napkin, cradled his head in her arms, and began singing a song to him:

“I’m sorry, Tracye,” Murphy said.

“What are you apologizing for?” She patted his stomach.

Murphy looked at me. “It’s your fault, Richard. No more off-roading with you.” He began to laugh.

“What’s so funny?” Overby said to him.

“I’ve had enough, Tracye. I’m leaving. I’m getting out of here right now. Good-bye.” He thrashed around on his back, kicking and laughing. He couldn’t even sit up.

Elrod, sitting in the front seat of the Expedition, began laughing, too. Their laughter drifted through the silence of College Lake. The men were connoisseurs of what I had done: I had ignored the advice of a police officer and driven two disabled men at high speed into the mud. They saw something familiar in my behavior.

I popped a beer and handed it to Elrod. “Are you okay?”

“Just fine.”

I opened a beer for myself. “There’s chicken in the cooler. Do you want some?”

He ate pieces of chicken with his gloves on, and asked me not to hand him any pieces that had sharp bones.

It was a cloudless day in spring, without a breath of wind. The Santa Cruz Mountains stretched into the distance, blanketed with many colors of green. Canyons wandered down through the mountains, jammed with the dark spires of redwoods. A flock of coots burst from the willows and flew straight across the lake bed, heading west toward the sea. Overhead, violet-green swallows dodged and looped. The birds were behavioral phenotypes, their movements controlled by their genes. A streak of dust appeared in the east, at the edge of the lake, and extended toward us: something moving fast. Speed of Light Towing was coming for us. A battered pickup truck with fat tires stopped a good distance away. A young man got out. He walked over to us, dragging a chain and stomping his feet on the sand as he went along, testing the sand. His name, it turned out, was Robert, and he was the same person I’d spoken with. He glanced at the Lesch-Nyhan men. “Hey, how are you?” he said in friendly way.

“Fine,” Murphy answered in a slushy voice.

Robert said to me quietly, “What’s with them?”

“It would take a while to explain,” I said.

“We’ll need to dig,” Robert added.

All of us (except Elrod and Murphy) got down on our knees and began scooping sand from under the vehicle with our hands, Robert working along with us. Ten minutes later, we’d dug a tunnel under the vehicle. Robert crawled into it and got the chain hooked into the chassis. He crawled out. “Start your vehicle,” he said to me. “Give it gas when the chain goes tight. If the chain breaks, watch out. It could come back through the windshield and cut your head off.”

He started his truck, gunned the engine. The truck shot forward in a running start, and chain snapped tight.

There was a sound like a gunshot; the chain had broken. It whiplashed back and hit the Speed of Light truck with a booming sound that echoed over the lake, leaving a dent in the tailgate.

Robert got out and studied the damage to his truck. He seemed philosophical about it. “I should’ve used the big one.” Then he reached into the bed of his truck and unfurled a massive chain—the big one. He dragged it slowly over to us, and got it attached. “This’ll definitely pull something out of here. I just hope it’s not your axle.” He floored his truck, the chain went tight, and the Expedition was yanked out, bouncing and fishtailing over the lake bed. Perhaps having Lesch-Nyhan syndrome is like being stuck in mud all your life while waiting for help that never arrives.

A COUPLE OF YEARS LATER, Jim Murphy came down with pneumonia, and he went downhill fast. When it was clear that he was dying, I called him to say good-bye. As he got on the line, I could hear a hubbub of voices in the background. A lot of people had come to see him, and they were milling around in his hospital room and in the hallway. He seemed to be handling his situation calmly. “I’ll be all right,” he said to me, and added, “Take care with your driving.”

Another day, before Jim Murphy died, I visited James Elrod. Tracye Overby, who was working as Elrod’s assistant that day, needed to change the silk liners he wore inside his motorcycle gloves.

Elrod did not like to see his bare hands. He asked me to hold his wrists while Overby removed his gloves. It occurred to me that I had never seen his hands. The hands that emerged were pale, with spindly fingers that had been gnawed close to the bone in places, and a finger was missing. “Danger,” he said. His eyes took on a strange, bright, blank look. He was staring at the right hand. His arm was tense and trembling. As if a magnet were pulling it, the hand moved toward his mouth. His mouth opened, wider and wider, baring his teeth…. “Help!” he called in a muffled voice.

We threw ourselves on Elrod. It took all our strength to restrain his hand. As soon as we got control of it, he relaxed. Overby got the gloves back on him.

“Nobody knows about this disease. Every day I’m hoping for a cure,” Elrod said. “I wanted you to see that.”