by Geeta Anand
“But the biopsy is a long way away,” John said, his voice pleading. “You have to give us some idea.”
The nurse hesitated, then said, “It could be something like muscular dystrophy, or something else …” Her voice trailed off.
John said February 12 would be fine for the biopsy, hung up, and looked at Aileen. “She says Megan could have muscular dystrophy. Do you know what that is?”
Aileen shook her head slowly, her auburn hair sliding over her cheekbones, which were blanched white with anxiety. Like John, she had heard of the disease, but she didn’t exactly know what it meant. To her, it sounded like the name of the disease for which people sold shamrocks for a dollar at the convenience store. Maybe it was the one for which firemen collected money in buckets at traffic intersections. Or was it the disease that Jerry Lewis raised money for in telethons?
Megan began to cry in the other room, startling them out of their tense silence. Aileen went to get her from her afternoon nap, burying the terrifying questions in the comfort of routine.
That night, Aileen put Megan to bed with her usual tenderness: sitting in the red upholstered chair in her bedroom, rocking her, gently feeding her the evening bottle, and singing her Barney songs.
John, however, couldn’t stop wondering about muscular dystrophy. The next morning, he drove to the Barnes & Noble in downtown Walnut Creek and bought four books on the disease. He spent the next day paging through them nervously, learning about the different types of muscular dystrophies. The most common, Duchenne muscular dystrophy, usually began to affect boys at about five years old, weakening their muscles steadily so that they couldn’t walk and eventually died. He looked in horror at a picture of a girl—who, with her dark hair and pale complexion, bore an awful similarity to Megan—walking with braces on her legs, a crutch under each arm. Nobody in his family had a physical handicap. It was unimaginable to think of his daughter needing crutches. How would she be able to play soccer, as he’d always imagined, or have her first awkward school dance with a boy?
For days, the books sat in a pile on his nightstand. He saw Aileen touch them once. She picked up the top book, looked at the cover picture of the girl with crutches, and slammed it back down, murmuring, “No.”
Eventually, he slid the books under his bed and out of sight.
On March 6, under the cloud of Megan’s uncertain prognosis, John and Aileen drove to John Muir Medical Center in Walnut Creek for the birth of their third child. Megan had had her muscle biopsy, but the results were still not in. Aileen’s parents, Marty and Kathy Holleran, had flown out from New Jersey and were taking care of John Jr. and Megan.
Aileen’s scheduled C-section, her third, went so smoothly that her doctor and John engaged in a lively speculation of the baby’s fatherhood in the operating room. “We got a moose here,” said the doctor, a handsome man only a few years older than John, lifting out the nearly ten pound baby boy.3
“What a big guy—just like his daddy!” replied John, who at five foot six was about the same height as Aileen, but had never minded a good laugh about his stature.
“Yeah, his real daddy must be a big man,” the doctor retorted. As John laughed, Aileen’s exasperated voice rang out from behind what he had taken to sarcastically calling the “batting cage,” the screen that shielded the surgery from her view. “Would you two mind?!”
That evening, Dr. Kong showed up at the hospital for the routine pediatric exam of the new baby they had named Patrick. No doctor had examined their other two children so closely. Kong seemed to spend forever scrutinizing every part of the five-hour-old baby boy. Finally, after an interminable twenty minutes, Kong handed Patrick to Aileen and said, “He looks great.” Aileen, smiling and relieved, cooed to Patrick as she let him nurse again. The doctor washed his hands and stepped out of the room, John following behind him.
“Dr. Kong, have you heard anything about Megan’s biopsy?” John asked in a hushed voice once they were out of Aileen’s earshot.
“I’ve heard some preliminary results,” Kong said, looking down. “But nothing for sure right now. It’s all very preliminary. Dr. Birnbaum will be calling you next week to discuss them.”
Patting John on the arm, Kong walked hurriedly away from him down the long corridor. John stared after him long after he’d turned the corner. Finally, he stepped back into the flower-filled room where Aileen was still nursing their new baby.
3
Diagnosis
March 1998
Oakland, California
Only a week later, John and Aileen arrived in the pediatric neurology wing on the first floor of the Children’s Hospital and Research Center. The waiting room that had been crowded on their last visit was empty. Aileen, two days out of the hospital, had insisted on accompanying John despite her mother’s urging that she stay home and rest. John was the more emotional one, and Aileen didn’t want him to be alone when he heard Megan’s biopsy results. They left the two older children at home with Aileen’s mother, and brought only baby Patrick so Aileen could nurse him if he woke up.
John carried Patrick in his car seat as they approached the reception desk to check in. This time, there was no wait. They were immediately ushered into a small back room, furnished with a small desk, an exam table, and three plush chairs lined up against the wall. A grim-faced woman sat in one chair, a box of tissues resting in the seat next to her.
Dr. Birnbaum stood up from behind the desk and introduced them to the seated woman.1
“This is Jill Cooper. She’s a social worker,” he said in his quiet voice. Foreboding struck John like a slap in the face, and he actually flinched. How bad must things be for a social worker to have been called? Megan must have a disease. It’s got to be her muscles. My God, will she never walk? Will she use crutches? Maybe she’ll be confined to a wheelchair for the rest of her life. He forced himself to stop. He would wait for the doctor’s assessment before speculating any further.
He and Aileen sat in the two open seats beside the social worker. John pushed Patrick in his car seat under the table—still, thankfully, asleep.
“How is Megan doing?” Birnbaum asked as he sat back down.
“She’s doing well, thank you,” John said. “She’s still not crawling forward, but I think she crawled backward a little bit the other day. It’s taken some time but I think she’s finally making progress.”
“Good, good. Well—I know you’re anxious, so let me tell you about the biopsy,” the doctor said. Then he paused and took a deep breath. “The lab tests found Megan’s muscle fibers full of something called glycogen. They found a lot of it. We think Megan has a lysosomal storage disorder called Pompe disease.”
“Is it serious?” Aileen asked, leaning forward in her seat, lines forming around her mouth as her face tensed.
“Yes, I’m afraid it’s very serious,” Birnbaum said. “This is a bad diagnosis. Pompe disease is a progressive disorder. It makes the muscles weaker and weaker.”
John and Aileen looked at one another, saying nothing. Muscular dystrophy had been a mystery to them when the nurse mentioned it as a possibility over the phone, but at least they’d heard of it.
“What causes this disease?” John asked at last.
Birnbaum picked up a big hardcover book from the desk and opened it to a page he had marked with a yellow sticky. He began to read aloud, sometimes breaking away from the book to explain. John noticed his hands were trembling.
“Pompe disease is an inherited genetic disorder. It is caused by a defective or missing enzyme,” he said. “Without this enzyme, our bodies cannot break down a very important carbohydrate or sugar called glycogen. Our bodies make energy at the cellular level by breaking down glycogen. In Pompe patients, this stuff, this sticky glycogen, builds up in the muscles. Patients get weaker and weaker. There are forty-eight other similar diseases, each of them caused by a different defective or missing enzyme that is needed to break down an important substance in our bodies. Luckily, all of these disea
ses are extremely rare. Pompe affects only one in forty thousand people, so your daughter’s case is actually the first one I’ve ever seen. There are three different forms of the disease: infant, juvenile, and adult onset, with the infant type being the most severe.”2
Birnbaum closed the book and put it down on the table. John and Aileen had followed most of what he was saying, but not all. He had held on to the worst part to share last.
“It’s a fatal disease,” he said softly, looking first at John, then at Aileen, then averting his glance from them entirely. “Most kids with the infant form of the disease don’t live to be two. I’m very sorry.”
Dropping her head into her hands, Aileen began to cry. The social worker handed them tissues. John blew his nose and reached over to put his arm around Aileen.
“Are there any treatments?” he asked, his voice shaking.
Birnbaum hunched over his desk and shook his head. “I went onto Medline—the most powerful medical research database there is—and I couldn’t find anything.”
John’s eyes fell on Patrick, still peacefully asleep in his car seat under the table. “Is there a chance he has it too?” he asked slowly, finding himself unable to look away from the soft curves of Patrick’s gently sleeping face.
“Yes,” the doctor was saying. “If the parents both have a certain genetic mutation, which you apparently do, there is a 25 percent chance each child might have it.”
“Oh, God,” John said. Aileen cried even harder.
Birnbaum finally brought his gaze back to them, meeting John’s eyes. John could see the regret in them, but also hopelessness. “I’m so sorry,” he repeated, his hands curling helplessly across the desk in front of him.
The doctor recommended they see another neurologist for a second opinion, and gave them the name and contact information of a Dr. Miller. Then he and the social worker stood up. Birnbaum said they would both be happy to answer other questions the couple might have later, and that they should call any time.
Driving home on Route 24 East, John’s mind raced uncontrollably. “The little men are at work in your head again,” Aileen would often say at night when he couldn’t sleep because he was thinking too hard. He remembered the crushing pain and loneliness he’d felt in the weeks after his father’s death, and the ache that came back each time he saw a father and son together. But even that early loss had not prepared him for this. One—possibly all—of his children had a fatal disease for which there was no treatment, let alone cure.
Outside, it was still windy and dark. He resolved that when they got home, he would call Aileen’s dad, Marty, and ask him to fly back out to California. Marty would help them figure out what to do. He was the go-to guy in Aileen’s family; every family had one. Marty’s mother had died when he was nineteen, and his father was so depressed that Marty was left caring for his two younger siblings. From then on, anybody in the extended family who needed anything would call on Marty. He had become a father figure to John, too, when he and Aileen began dating in high school. Yes, that was it. Marty would know what to do.
For a moment, John was comforted. Then he winced at the thought of having to actually tell Marty such terrible news. How would he tell his friends? His mother?
“What if the doctor is wrong?” he blurted to Aileen.
“Let’s just not go there right now,” she said. She had stopped crying and was staring fixedly out the window at the gray clouds whipping by.
Understanding, John turned on the radio. He liked to talk out his worries, but Aileen preferred silence or diversion. Natalie Merchant’s song “Wonder” was playing. It was a popular song, and he’d heard the song before, but today, for the first time, he listened to the words. A high voice, filled with joy and optimism, sang about the gifts of a child and knowing she would thrive despite the visits of many doctors. “With love, with patience, and with faith, she’ll make her way,” Merchant sang. His heart lurched, and tears spilled onto his cheeks.
“Oh, John,” Aileen said, looking at him at last. “Why don’t you pull over, honey, or you’re going to have an accident.”
John kept driving. “I just want to get home and hug Megan,” he said.
4
Hope
Spring 1998
Walnut Creek, California; Great Neck, New York
For all of his thirty-two years, John had met any blow he was dealt with the same steadily determined response—to try to fix it. He had tried to fix his father’s death for his mother by becoming her confidant, her financial adviser—the perfect son. When his grandfather lost his health insurance, John, still in law school, had fixed that, finding him a new plan and paying for it by adding several thousand dollars more to his student loans. Since childhood, his family’s finances had been shaky, and he was fixing that with his Harvard MBA and the highest-paying job he could find.
Now, as he absorbed Dr. Birnbaum’s diagnosis—that his precious Megan had a deadly disease for which there was no treatment—all John could think about was what he could do to find one.
That night, after Aileen fell asleep with Patrick close by in his blue plaid bassinet, John sat down at the sofa table that served as a desk in their bedroom and turned on the computer he had bought and linked to the Internet just a week earlier. He typed “Pompe disease” into the window of a search engine, and with the click of a button, entered a new world of disease and drug discovery—one that he would not leave for the next nine years.
Pompe disease, he learned, had been discovered in 1932 by Dutch pathologist J.C. Pompe. Dr. Pompe had performed an autopsy on a seven-month-old baby who had died of heart problems, and had discovered that the tissue was overflowing with a thick, sticky substance called glycogen. He was the first to make the connection between the glycogen oozing out of the baby’s muscle cells and the symptoms of the disease—the enlarged heart and weakening of the muscles that eventually led to death.1
But World War II halted Dr. Pompe’s work. He had joined the Dutch resistance, and the Nazis found a secret radio transmitter in his lab. He was arrested and murdered. Over the next two decades, doctors and scientists began to recognize and report more patients with what came to be called Pompe disease. Many of those diagnosed with infantile Pompe displayed symptoms similar to Megan’s—the early signs of weakness in their legs that fell into the signature Pompe “frog” position when set on a flat surface. While the disease was degenerative and the patients steadily grew weaker, Pompe seemed to affect some muscle groups more and earlier than others. Along with the legs, the facial muscles tended to rapidly weaken, as did their hearts and lungs, but patients usually retained strength in their arms for longer. In 1963, the Belgian scientist Henri Hers discovered the enzyme acid alpha-glucosidase was deficient in patients with Pompe disease.2 In the 1960s and 1970s, researchers in Europe and the United States began to discover the more than forty other similar diseases, each caused by a defect in an enzyme that processed waste material within the region of the cell called the lysosome, which functioned like a garbage disposal. This enzyme defect led to the buildup of the waste material it was in charge of breaking down.
By the 1980s, scientists had developed a new technology to decode genetic material, and they were trying to make laboratory versions of genes and other proteins. This set off a race among the handful of scientists working on Pompe disease to describe the genetic composition of the gene encoding the enzyme deficient in patients. If they knew the genetic code of the enzyme, acid alpha-glucosidase, scientists believed they could produce an artificial version in the lab and infuse it into patients who couldn’t make it properly. Finally, they would be able to offer patients some hope.
In 1986, Dr. Rochelle Hirschhorn, a professor of medicine at NYU Medical Center, published a portion of the gene. The Dutch researcher, Dr. Arnold Reuser, followed two years later with a description of the entire gene. Hirschhorn came back to expand on Reuser’s work and correct parts of the gene he had described incorrectly.3 Reuser and others began to look
for a way of producing large enough amounts of the enzyme to treat Pompe patients.
Reading this, John’s hopes rose for an instant. Then, as he clicked on links to further articles, his heart fell again.
Making biological matter for medicinal purposes, he found, was challenging and expensive. Reuser spent several years trying in vain to find a company willing to invest the millions of dollars required to produce the enzyme for a disease with five thousand patients, at best. The financial incentive didn’t seem to match the enormity of the up-front investment needed—and John, with his Harvard business degree, could understand the awful logic of the financial decision. Reuser collaborated for a time with a physician-scientist of Taiwanese origin, Dr. Y.T. Chen, at Duke University Medical Center in the United States, who was also interested in making an enzyme replacement therapy for Pompe disease.
Then, in the early 1990s, Genzyme Corporation, a tiny U.S. biotechnology firm, proved it was possible to develop an enzyme replacement therapy for a disease affecting only a few thousand people and make a profit. Genzyme brought to market an enzyme treatment for Gaucher disease, a related disorder that was caused by a defect in the lysosomal enzyme responsible for processing fats, or lipids. Genzyme grew rapidly into a profitable business, even though its therapy treated an estimated four thousand people by charging each patient a staggering average cost of $200,000 a year.
Encouraged by the success of the Gaucher disease drug, Reuser and Chen approached Genzyme separately and tried to interest the company in investing in a Pompe treatment. But the company was still small at the time, and senior management felt they couldn’t take the risk.4 The two researchers eventually found other corporate sponsors. Reuser teamed up in 1993 with a Dutch company, Pharming, which specialized in altering the genes of animals so that they produced milk containing human forms of enzymes needed for therapeutic uses. The company bred rabbits in which one gene had been added, so that the milk they made contained a human form of the acid alpha-glucosidase enzyme. The enzyme was purified out of the milk of hundreds of these transgenic rabbits.