Blood Matters Read online

  Puffenberger was now finished with articulating this part of his scientific platform and willing to entertain questions. He was master of the Mennonite and Amish genome. He had identified the genetic causes of over one hundred diseases and will probably have identified a dozen more by the time this book is published. In the previous generation of geneticists, scientific reputations and entire careers were made on the basis of a single such discovery. Puffenberger was one of the first representatives of a new generation, one that treated genetic analysis as just another diagnostic tool. This made him the perfect partner for Morton, who dealt with rare genetic disorders as just another illness to be treated and managed.

  ***

  The drive to Susie’s house in Lancaster County took me past picturesque Amish homes, the ones that stand pure white against the green hills, the ones with the large barns and tall silos that, when the narrow road was empty except for a horse-driven buggy or two and my rental car, made me feel like I was time-traveling. Susie’s house belonged, unmistakably, to the second half of the twentieth century.

  There was linoleum on the floors, and a ramp for the disabled up to the porch. As in other Amish homes, there was no electricity—or, rather, no hookup to the municipal power lines: There were several electrical devices in the home, including a wheelchair, but these operated on batteries that could be charged using a generator planted out in the small barn. Susie talked to me while she sewed—she was working on a simple quilt, laid out on a board by the window, to make sure she used as much light as there was in a day. She worked a large needle at an even pace, looking up at me through her large aviator glasses most of the time. She was a rare sort of storyteller: even-voiced, as though detached, but so true to her narrative that, whenever she came to the birth of one of her children, I could not guess whether this would turn out to be a healthy child or an affected one.

  Susie and Amos’s first son was born in 1970, two years after they were married. That made Elmer thirty-five by the time I met his parents. He was grown-up and married: He was fine. The next son, Levi, was born in 1973. “He was a fussy baby, and we could see that he was not developing so fast,” Susie said. “He gradually lost muscle control. Eventually it seemed that some of his muscles were doing the opposite of what he wants them to do.” When this baby was nine months old, the family began making the rounds of doctors trying to figure out what was wrong with their son. “At the end of all those tests they said there wasn’t much they could tell us. And I asked about cerebral palsy, and they said, ‘That’s probably what he has.’ And I admit I wished they would just come out and say it.” Whatever it was, though, Levi would never be like other children. The Amish have ways of thinking about children like that. They call them “God’s special children” and similar names. They believe there is a separate heaven reserved for these children, who usually die quite young. They talk about this, and they do not usually talk about the crack that appears in a young couple’s world when they realize that their child will not walk, talk, or feed himself.

  “We had our time of acceptance,” said Susie. “We realized he was a sweet little boy, even though he could not talk like other children.” The hardest thing about taking care of this baby was feeding him: His muscle problems meant that he could neither swallow nor easily keep food down. Keeping the little boy nourished was a round-the-clock occupation.

  “In 1975 we were blessed with another little boy,” said Susie. She talked with the particular Amish accent: throaty and deliberate. The Amish speak to one another in a language they call Dutch, which is the local way of pronouncing “Deutsch”: The language is in fact a variant of German. Since most Amish are educated in Amish schools, their English, while fluent, bears the mark of a second language: Their speech is exceedingly literary. “Everything appeared fine at first,” she continued. “Then, when he was six and a half months old, he got a cold. Just a regular cold. When we thought he was recovering from the cold, we put him down for a nap. And he slept and he slept, and we finally woke him up, but it was quite a different little boy than the one we had laid down. He was completely helpless. He had been just the most playful little boy, and now he couldn’t use his hands or hold up his head.”

  It was winter. The roads were icy, which made it very difficult to get to the hospital using a horse and buggy, with its thin wooden wheels (calling a doctor was not an option, since there was no phone). They did make it to the hospital, though, and got another confused bunch of diagnoses, including pneumonia, which was not confirmed by an X-ray, and encephalitis. When Susie went home with baby Sylvain ten days later, all the doctor could tell her was that her son was very sick and might never recover.

  “So we had two little boys to take care of now,” said Susie, and, uncharacteristically, looped back in her story to her memory of her third son’s awakening from that nap. “When he first woke up, he clearly wanted to hold up his head and start playing, but he couldn’t. And he just cried, heartbroken, and he would cry every time. Apparently, somewhere in his brain he remembered playing.” Babies can feel heartbreak, just like their parents. After a while Sylvain seemed to give up his memory of playing, and later he learned to lift one of his hands and one of his feet, and this made him smile. “Oh, he was just the sweetest little boy. People were afraid to hold him, but everybody loved him.”

  Susie and Amos’s fourth son came along two years after Sylvain’s birth. “The doctor assured us he was okay. The doctor thought I was just overanxious, but by this time you start to wonder.” When Steve was eight weeks old, he was diagnosed first with an ear infection and then with meningitis. By this time Susie knew enough to be leery of diagnoses: “He just didn’t appear as sick as you’d expect with meningitis.” After they left the hospital, Steve seemed recovered but not quite: The parents noticed that his fontanel was inflamed. In the late 1970s CT scans were just coming into use, and baby Steve got one. “The doctor said, ‘The news is good and bad. He doesn’t have hydrocephaly. But we found a lot of brain atrophy. I’m afraid he is going to be just like your others.’

  “I don’t know if you have any idea what we were going through by this time,” said Susie. I did not answer and waited for her to continue. “I can tell you straight out,” she said. “We had a hard time. With ourselves. But we had our hands full.” They had four small children, three of whom were severely disabled.

  “That winter we went to visit grandparents,” Susie said. “I had the baby in my lap, and the two handicaps were on a mat in the back. All of a sudden my husband stops the carriage. He drove the horse into a snowbank to stand better. And I said, ‘What’s wrong?’ He said, ‘Something is not right back there. Sylvain is not lying there like he was.’ He grabbed him—and there seemed to be nothing there, no breathing, nothing, and I quick gave the baby to Elmer—he was seven years old at the time—and tried to do mouth-to-mouth. I didn’t really know how to do it, but I tried.” Eventually they knocked on a door, someone called a doctor, the doctor came and said that there was nothing to be done.

  Susie told me in detail about the days that followed. There was a record snowstorm. It was nearly impossible to get to the cemetery. The body lay in their home for four days. It took the efforts of the whole local Amish community, and a tractor and plow, to enable them to bury Sylvain. At the cemetery, they had to leave the tractor, and shovel by hand because they could not see the gravestones for the snow. “It looked like a white room, because the snow was over our heads,” said Susie. The blank whiteness seemed the perfect image of her grief. Without pause, she went from describing the cemetery to describing the way she and Amos felt. “And when he passed, it seemed as though a part of us was left there at the cemetery. But people were nice and they came to visit us, and eventually we came to accept it. Levi had a hard time: It seemed he missed his brother so much, and he had a hard time because he couldn’t even speak.”

  In the summer of 1979 Susie gave birth to a daughter, Livanna. Four days later Levi died suddenly.

  “Whe
n she was about three and a half months old, I told the midwife that I’m not quite sure about her, I don’t think she is quite as active as other children her age. She looked at her and the doctor looked at her, and they both told me I was just overanxious.” Susie had been overanxious like this before, and she had been right. “A month later I came for a checkup, and the doctor said, ‘How do you feel about her now?’ I said, ‘Now I don’t need you to tell me, I know there is something wrong with this baby.’” Susie showed the doctor just what was wrong: The little girl could not kick with her legs; when she reached out, her movement was slow and her arm stiffened; if she wanted to grab a toy, she visibly had to struggle to get her hand into position. By this time Susie was ready to try something new. She told the doctor she was switching the baby to soy-based formula. This proved a good idea: Livanna started gaining weight faster.

  “So. We accepted her. She was a cute little girl. She wasn’t as helpless as Levi and Sylvain were. By this time Steve had started walking—it wasn’t the normal kind of walk, he fell a lot.” But he was surprisingly self-sufficient for a baby who had made his parents feel so hopeless. He learned to feed himself at the age of twenty months. At two, he started speaking. Physical therapy seemed to help him learn to walk. Livanna compensated for her lack of muscle control as well: At six months, she started pulling herself around by her hands, which would serve her well in the future, too, since she never gained control of her legs. Though the children had some difficulty making themselves understood, their comprehension was clearly no worse than that of other children their age—confirming Susie’s sense that the two children she had lost, Levi and Sylvain, had been quite aware of all that went on around them but simply lacked the ability to express themselves in any way.

  When Livanna was three years old, Susie gave birth to Ruben. “I thought there was better motion in his movements: He started holding his head well at six weeks, he squirmed well. I thought he was okay. When he was four months old, I got a walker at a yard sale. My husband said I was tempting fate. He got whooping cough, but he maintained muscle control. Everything looked fine. And the wonder of it stays with me to this day, because it stayed this way!” This was Susie’s one story with a surprise ending: Ruben was a healthy child who grew up to be a healthy adult. “I think everybody rejoiced with us that we finally had a child who could be okay.”

  Alvin was born three years after Ruben. “He gained slowly, but doctors felt he would be okay, and it looked promising.” With Ruben healthy and Steve and Livanna doing well in grade school—Livanna never learned to walk but picked up reading easily when she was five—Susie may have lost some of her vigilance. “When he was one year old, he got diarrhea and got over it. Six months later he got it again, and that time it didn’t turn out so well. He lost his muscle control. When we got to the doctor’s office, we could barely wake him up, and when we did, he couldn’t hold up his head. He’d been starting to talk and he was feeding himself, and now he could not hold up his head.” A familiar nonsensical sequence followed: a misdiagnosis of meningitis, a referral to Johns Hopkins, where the doctors, who were by now familiar with the family, had nothing new to say. “We all cried, as though he’d died.”

  Little Alvin cried and thrashed around constantly. Phenobarbital only made him worse. “It almost got the better of us for a while. We tried to bottle-feed him, but he was putting too much energy into sucking, getting just one ounce an hour. When we spoon-fed him, he tried to grab the spoon, because he’d been feeding himself, and he could do nothing with it and it broke his heart. We put him on the floor: He tried to crawl and fell on his face.” Susie remembered she had some medication left over from Levi, who had been dead for eight years. It was Valium, and it worked by settling Alvin down enough to enable him at least to eat.

  In 1988, when Alvin was three, Livanna was nine, and Steve was eleven, and Levi and Sylvain had been dead nine and eleven years respectively, a beat-up car pulled up in Susie and Amos’s driveway. “Amos first thought he was a feed salesman,” said Susie of her first encounter with Holmes Morton. “And he came in and told us that he thought he knew what was wrong with our children. Now this just doesn’t happen, a man doesn’t come to the door and tell you what’s wrong with your children.”

  ***

  Holmes Morton had been working at Children’s Hospital in Philadelphia. He had graduated from Harvard Medical School—this after forgoing college to work in the Merchant Marine, then serving in the navy, then deciding to study developmental neurology and entering college at twenty-five. So by the time he came to Children’s Hospital, Morton was in his late thirties, with a wife and three children. He came across a blood sample drawn from a boy in Lancaster County who suffered from a mysterious debilitating condition. “His story was—and what had fascinated me about the case—was that he had learned to sit up and walk and then he became ill and within a few hours he was disabled.” The boy was now four or five years old, and his diagnosis was “cerebral palsy”—in his case, an umbrella term that simply meant he had suffered neurological damage.

  Morton used some technology that was new at the time and diagnosed the boy with glutaric aciduria type 1 (GA1), a disease that was considered so rare in the late 1980s that even most specialists had never seen a patient with it. It is a recessive disorder that causes the body to be unable to process certain amino acids, which build up. Much like with maple syrup disease, the body is set up to go into overdrive and fail when anything upsets its metabolic equilibrium. When a child with GA1 develops an ordinary bacterial or viral infection, he is likely to suffer a stroke that will do irreparable damage to the basal ganglia, the parts of the brain that are responsible for controlling movement and perhaps for other functions (the caudate nucleus, which is affected by Huntington’s disease, is a part of the basal ganglia).

  Almost no one had seen a person with GA1, but Morton decided to go take a look. He took a day off, drove the couple of hours to Lancaster County, met the boy and his parents, and asked them if they knew of other children with similar symptoms. They said they knew a lot of them. “So I just came out and started finding these kids,” Morton said. “And by the end of that summer I had diagnosed twenty cases, within all the major family groups of the Amish.” GA1 would turn out to be as common among the Amish as maple syrup disease is among the Old Order Mennonites: Roughly one in ten people is a carrier.

  The Amish had long held a fascination for geneticists: They were a closed population, they obviously had a number of genetic disorders common among them, and they were generally willing to cooperate with researchers. Most people I met in Lancaster County explained this surprising acceptance of modern medicine by saying that the Amish culture is, first and foremost, pragmatic: While something like television is rejected because it may distract people from their work, their faith, and their community, modern medicine, which can potentially help keep Amish people healthy, does not fall into the same category. So for years genetic researchers had taken blood, urine, and tissue samples from the Amish, especially those who were apparently affected with hereditary conditions. Holmes Morton found out that Victor McKusick, one of the world’s best-known geneticists and author of Mendelian Inheritance in Man, the bible of medical genetics, had visited the same households Morton was visiting now and had not figured out what was wrong with the children. Glutaric aciduria type 1 among the Amish became Holmes Morton’s own project.

  Children’s Hospital did not encourage his research, so he left, finding a temporary home at the Kennedy Krieger Institute in Baltimore under Hugo Moser, a patriarch of neurological genetic disorder research who was portrayed by Peter Ustinov in the 1992 film Lorenzo’s Oil, about a little boy who suffers from adrenoleukodystrophy, another inherited metabolic disorder that destroys the central nervous system. “Hugo gave me a little bit of money to feed my family for the year,” Morton told me. “And at the end of the year Hugo put in a competing grant with mine with the National Institutes of Health. He is a pretty famous guy, so it
was pretty obvious to me that I wouldn’t get the money.”

  By this time Morton had spent a year tracking down Amish families affected by GA1. “He told us what he knew about glutaric aciduria type 1,” Susie told me of the day her husband mistook Morton for a feed salesman. “He came back that evening to collect urine samples. He came back after the weekend and said, ‘Susie, I found what I expected.’ Over the weekend, I had cooled off. I thought, now this is just another doctor who thinks he knows. But now, I tell you, I had to sit down.”

  Morton put Susie’s sick kids on low-protein diets and riboflavin (vitamin B2). They improved little, if at all: The damage to their brains was indeed permanent. But he started testing babies and new-borns in Amish families, sometimes managing to warn the parents in time to restrict the child’s diet sufficiently to prevent a stroke. By the time he failed to get the federal money, he was already treating children in Lancaster County and could not stop. So in the spring of 1989 Holmes Morton and his wife, Caroline, set up a nonprofit organization called the Clinic for Special Children, which was a little grand for an operation that was limited to Morton’s car. They figured the Amish and the Mennonites, who had a system for raising money to pay large medical bills—they generally have no insurance, not even Medicaid, even though they pay taxes—would be able to gather some money to help care for their “special children.” In September of that year the Wall Street Journal printed a front-page story on the effort, drawing more than half a million dollars in donations that essentially launched the clinic. The Mortons moved their office from Holmes’s car into a space provided by Lancaster General. In another year, men from the local Amish and Mennonite communities held a barn raising—the sort shown in the movie Witness, where hundreds of men in identical black single-strap trousers and primary-color shirts work like ants to erect a building in a day. The clinic was built on land that belonged to an Amish farmer whose granddaughter Morton had treated for GA1. Thereafter the clinic survived on small fees it collected from patients, large and small donations, and regular fund raisers at which local residents auctioned to the larger public their quilts, buggies, and other handmade artifacts to bring in as much as a third of the clinic’s budget. The most expensive equipment in the clinic, which had allowed Erik Puffenberger to take his colleagues and patients into a new era of genetics, had been donated by the manufacturer.