by Geeta Anand
At around the same time, Chen teamed up with a Taiwanese company called Synpac Pharmaceuticals. He made acid alpha-glucosidase in giant, stainless steel containers similar to those used to produce beer. This was fast becoming the standard method for making biotechnology products. Manufacturers filled the containers, called bioreactors, with cells taken from the ovaries of Chinese hamsters—known in science lingo as CHO cells—which had been genetically altered to produce human versions of acid alpha-glucosidase.
Nearly three hours had passed when John found a link on the Internet to a press release from Duke University. Issued on February 14, Valentine’s Day—barely a month earlier—the press release announced that Chen planned to test his experimental enzyme in babies as part of an early clinical trial. The release said Chen had tested his experimental enzyme in Japanese quails afflicted with Pompe disease who were so weak they hadn’t been able to flip over or fly. “The high dose GAA treatment improved muscle strength so much that both birds could right themselves when flipped on their backs. One bird could even fly a short distance,” John read to himself. Based on the results, Chen was working with the U.S. Food and Drug Administration to begin a clinical trial, and “within this year, Chen and his colleagues expect to treat children born with the rare and always fatal Pompe disease.”5
With a few more clicks, John read that Pharming, the company allied with Reuser, was also preparing to launch a clinical trial of its enzyme in four babies with Pompe disease. These developments were so new that even Dr. Birnbaum had been unaware of them.
John pressed the print button and leaned back in his chair, closing his eyes and breathing deeply. He had spent the afternoon after Birnbaum’s diagnosis driving alone around Walnut Creek in his rented green Pontiac Bonneville, crying and praying. “Please God, just let Megan live until her second birthday,” he had begged. For all of John’s belief in his own powers of will, he was also deeply religious. Raised in the Catholic church, he had been not only an altar boy, but a family friend of the parish priest, who often ate dinner with his family. During stressful times in his life, John often attended Mass every day.
The evening after Megan’s diagnosis, John had driven to San Francisco Airport to pick up Aileen’s dad, who had flown cross-country as soon as he heard the news. “I don’t know how, but we’re going to figure this out, John,” Marty had said gruffly, staring straight ahead as they drove home. He still seemed to be stunned by Megan’s diagnosis. John had said nothing in response, eyes trained on the blackness of the road ahead. He wanted to say something to Marty, to comfort his father-in-law or allow the older man to comfort him, but he could find no words to reach out through the gloom.
Now, here it was. Something real, a triumphant flash of scientific discovery to brighten the doctor’s dire prognosis. He stared at the printer as it churned out word after word, page following page of information on Pompe disease, and hope flooded into his chest, his heart, his soul. He wanted to share the news.
“Aileen,” he whispered, looking into the dark corner where his wife lay sleeping in bed. She didn’t stir, but Patrick began to cry in the bassinet beside her. Aileen sat up with a start and blindly groped for the baby. John picked up the pile of papers from the printer and walked over to the side of the bed, reading from the press release announcing Duke University’s clinical trial.
“Look. Wake up and look at this. This is amazing. It says that there are some doctors at Duke who are working on Pompe.”
Aileen, still half-asleep and nursing Patrick, just stared at John, struggling to comprehend. In his excitement, John went on, “And there’s more. It says a Dr. Chen at Duke is working on a treatment for Pompe. He has an enzyme already created in his lab. He gave it to some Japanese quails with Pompe, and it worked.”
Aileen cut in. “He gave this enzyme to what?”
“To quails—you know, birds,” John responded.
“Yes, John. Thank you. I think I know what a quail is,” she said grumpily, lapsing into a sort of mock-snappiness. “But what does that have to do with Megan’s disease?”
“It means, smartass, that some bird that somehow has the same disease and the same missing enzyme as our daughter, got this enzyme—and it made the bird stronger. Look here, it says the birds actually flew.” He stabbed a finger at the printed paragraph, and waved the papers elatedly in the air. “Can you believe it, the goddamn bird flew!”
Aileen asked cautiously, “What does this mean?”
John looked her in the eye, brushed his newborn son’s hair, and said slowly, “It means hope, Aileen. It means hope.”
“See here, listen,” he said, reading from the press release. “ ‘Based on these results, we believe this enzyme is a promising therapy for the human form of Pompe disease. Dr. Chen said he will initially attempt to treat only a small number of children. If it is successful, children will need a supply of the enzyme for their whole lives.’ ”6
Aileen, sitting up straight, lifted Patrick over a shoulder to burp him and told John to slow down. Understanding flashed across her face as she listened, and her eyes brightened. Her husband was telling her there was a way to lift the death sentence on their precious Megan. Aileen gently lay Patrick back in his bassinet and stood up shakily, sliding her arms around John and squeezing tightly.
“What do we do now?” Aileen asked, excited but uncertain. She knew John would have the answer. Like her dad, he always seemed to know what to do, to take charge, to make things happen.
“We call Duke,” he whispered as they held one another. They stood together for a long time until Patrick’s fussing grew into a full-scale wail. Aileen sighed, sat back down, and began to nurse their son from the other side, and John went back to the desk to study the printouts. It was a pattern that had become a foundation in their lives: she nursed the children with patience and love; he began to think and to plan.
That weekend, John went to Kinkos and put together a dozen booklets with tan covers that read “Summary of Medical Records of Megan Kathryn Crowley.” He stayed awake until early Monday morning so he could call Dr. Reuser, the Dutch scientist at Erasmus University whose work concentrated on extracting the enzyme from rabbit’s milk, when he might be arriving at work at 9 a.m. in Rotterdam.
“I am calling from the United States of America to talk to Dr. Arnold Reuser,” John said, speaking slowly and loudly.
“Oh, you want Arnie,” said a voice in fluent English. “Hold on.”
Within a minute, Reuser, warm and sympathetic, was saying that yes, he did work with Pharming, but he was a research scientist and didn’t treat patients. He advised John to take his daughter to see a Dr. Alfred Slonim at North Shore University Hospital in Manhasset, a suburb of New York City. “Dr. Slonim is an expert at treating the disease, and he is also working with us to plan a clinical trial of our enzyme treatment in the United States,” Reuser said. Companies, it turned out, collaborated with doctors not only for their expertise, but also for easier access to patients for clinical trials.
Two weeks later, on April 1, John, Aileen, and Megan pulled up at the Inn at Great Neck, a new five-story brick hotel a few miles from North Shore University Hospital. It wasn’t where you would expect to bring your child to be examined by a physician, but Slonim’s nurse had told them that he was having meetings there that day. Also attending would be a Dutch physician who was an expert in treating Pompe and business officials from Pharming to plan the clinical trial in the United States. Based on John’s description of his daughter’s symptoms, the nurse said Slonim suspected Megan might have an unusual form of Pompe disease—and one in which he had a particular interest. His Dutch visitors had never seen a patient with that variation, and he wanted to show them one. John had happened to call at the right time.7
Luck and good instincts had led Slonim into an area of study that would eventually make him an expert on Pompe disease. An orthodox Jew, he had grown up in Melbourne, Australia, and spent his first years in medicine as a pediatrician in Israel. I
n 1974, he came to the United States to take a postdoctoral position in endocrinology at Vanderbilt University. One of his first patients there was a sixteen-year-old girl who suffered from a disease similar to Pompe. The girl had developed severe hypoglycemia, or low blood sugar. There was no treatment for the disease, so Slonim had tried the next best thing—experimenting with the girl’s diet. On Slonim’s low-carbohydrate diet, supplemented by tube feedings of formula at night, the girl was able to go to school for the first time.
Word of the “miracle” spread, and soon families of children with that disease and related disorders, including Pompe disease, began to call. The doctor’s diet-and-exercise program seemed to slow the progression of a range of related disorders.
Several hundred patients were born with Pompe each year in the United States, but many died as infants, before their parents even knew what was wrong with them. Even if the babies were diagnosed, doctors usually sent them home with no hope because medical textbooks listed no treatment. Slonim’s patients found him through word of mouth or the Internet, which had just begun to become a mainstream resource. He had treated about thirty patients with Pompe before John called.
With Megan in a stroller, John and Aileen rode the elevator to the second floor of the Inn at Great Neck. John led the way down the hallway to the conference room, and Aileen followed, her knuckles white on the handles of the stroller. John knocked on a green door, and they entered the room to see six people sitting around a long, dark table covered with papers. A broad-shouldered, balding man who looked to be in his sixties rushed toward them, hand outstretched.
“I’m Alf Slonim,” he said, with a big smile and a pronounced Australian accent. He shook hands vigorously with John and Aileen, then immediately dropped into a crouch in front of Megan’s stroller.
“Hello, little girl!” he boomed, his face only about six inches from hers. Then, in a quieter tone, he muttered to himself, “Yes, lovely, beautiful little girl. Just beautiful.”
Megan, in her pink windbreaker and matching bow, leaned forward in her stroller, staring at him.
“What a pretty pink bow, little girl,” he continued, again speaking to Megan. “You certainly took a long trip to come see me.” Then he glanced to the side and said wryly, “Your daddy was most persistent with my nurse, making sure you got here,” drawing a laugh from John and chuckles from several of the seated men.
“What’s your name, little girl?” he asked, his accent making the word name rhyme with thyme.
Megan looked up at Aileen and grunted, wanting her mother to answer the question.
“This is Megan, Dr. Slonim,” Aileen said, unclenching her jaw into a nervous smile.
Slonim’s age, his gentle manner, and his kind face reminded John of his mother’s father, his grandpa, the man who had helped raise him when his father died. The two were inseparable for most of John’s childhood, and had remained close until Frank Valentino’s death two years earlier. Instinctively, John felt that this Dr. Slonim was a good man, someone he could trust. He seemed familiar even though they had only just met.
John looked over at the conference table, curious about the identity of the others in the room.
“This is a good time to break,” the man at the head of the table was saying to the others. He was tall and heavyset, with a full head of brown hair and a Texas drawl. “Randall House,” he said, coming around the table to shake hands with John and Aileen, his gold Rolex glinting in the overhead lights. “You talked to my wife on the phone several weeks ago.”8
John recognized the name. He had found Mr. House’s phone number on the Internet the night after Megan’s diagnosis. He’d read that Randall and his wife Marylyn had founded an advocacy group, the Acid Maltase Deficiency Association (AMDA) three years earlier, when their daughter was diagnosed with Pompe (also known as acid maltase deficiency in its adult form). Tiffany, now fifteen, had what was then known as the juvenile form of the disease. It was less severe than the infantile type, but she, too, wasn’t expected to live into adulthood. Patients with the infantile form made virtually no enzyme correctly, but those with the juvenile and adult forms actually made between 1 and 40 percent of active enzyme themselves. Still, it wasn’t enough, and glycogen built up sufficiently by adolescence or adulthood for symptoms to develop—usually weakness in the legs and lungs. Where the hearts of infants with Pompe were severely enlarged and usually failed by age two, juveniles and adults often started off with no cardiac problems. For them, the disease progressed more slowly, but over time they too had difficulty breathing and developed cardiac problems that led to early death.
The Houses owned a successful construction business in San Antonio, and they had used their personal fortune to finance the first conference for Pompe researchers in 1996, drawing top scientists and doctors from around the world to San Antonio.
“Yes, Mr. House. It’s great to meet you,” John said, looking up at him eagerly. “I would very much like to be involved with your group.”
“Well, we would very much like your support,” House said. “But the best thing for you to do right now is to look after your daughter here.”
Slonim interrupted, asking John if Mr. House and Ans van der Ploeg, a physician and Pompe expert from the Netherlands, could remain in the room while he examined Megan. John and Aileen nodded.
“Do you mind?” he asked Aileen, reaching down to lift Megan out of the stroller.
“No—please,” Aileen said, stepping back. Megan didn’t resist as the doctor placed her in the middle of the conference table, surrounded by piles of papers. As Slonim and John pushed the papers to either end of the table, Aileen undressed her daughter. John glanced at the papers he was stacking. “Pharming Study Draft Protocol,” he read on the cover of a document, eyes widening.
“Megan, can you lift your arms, please?” Slonim asked.
Megan, stripped down to her diaper, raised her arms, looking over at her mother and father.
“She’s extraordinarily compliant,” Slonim said to them.
“Yes, Doctor, she likes to show off how smart she is,” John said with a laugh.
“Just like Daddy,” Aileen tweaked him, relaxed enough now not to miss the opportunity to make fun of her husband.
“Ouch, Aileen,” John said, wincing and chuckling. He winked at Megan. “But Mommy is right, isn’t she, Megs?”
“Very good,” Slonim said to Megan as she nodded in agreement with her father. “You are one smart little girl. Now, can you roll over?” he asked. Aileen put Megan on her stomach. Megan promptly flipped over onto her back.
The doctor pulled a stethoscope out of his briefcase, put it in his ears, and listened to Megan’s lungs and heart, frowning slightly. She flinched at the coldness of the metal and looked up at her mother inquiringly. Slonim felt her stomach with gently splayed fingers. “Her liver is enlarged, as we would expect,” he said, and made a note on a chart on the table.
“Let’s move to the floor now,” he said. “Let’s see if she can crawl.”
Murmuring encouragement in Megan’s ear, Aileen gently lowered her onto the carpet. John set his daughter’s Winnie the Pooh stuffed toy a few feet away. He held his breath, watching, as Megan rose slightly on all fours and pushed with her arms, sliding back a little. Her legs didn’t move at all, and she began to cry.
“Oh, Megan,” John said, picking her up and hugging her. “She can’t crawl,” he said, looking up at Slonim.
Aileen unclipped the Pooh pacifier that hung from Megan’s jacket and popped it into her mouth, shushing her. There was nothing she could do about her daughter’s wrenching weakness, but at least she could allow her maternal instincts to meet an immediate need.
“Is she able to swallow food?” the doctor asked.
Aileen nodded.
“Can I see her x-rays?” he said. John handed him the x-rays taken in California two weeks earlier.
Slonim beckoned to van der Ploeg and House to come over and look over his shoulder. “Notice o
n the outside that she’s reasonably strong. But notice here the profound enlargement of the heart,” he said in a low voice, his forefinger tracing the shape on the transparency. “It’s lying on the lungs, which could very soon cause significant respiratory issues.”
He pulled out chairs for John and Aileen. They sat down, Aileen dressing Megan on her lap as John questioned the doctor.
“Dr. Slonim, it’s still so hard for us to believe Megan is sick. She looks so normal. Tell me, if you hadn’t been told she had Pompe, would you have known just by looking at her?”
“John, I’ve got to tell you, she looks good,” Slonim replied. “But there are the telltale signs for those of us who know. See how her face is a little bit flat and how her mouth is almost always open a little. And I bet you she doesn’t smile much, if at all. This is all because her muscle tone is weak. And do you see how you can always see a little bit of her tongue when her mouth is open? All of our Pompe children look like this.”
John stared silently at Megan, shaking his head, as Aileen pinned the pink bow back in her hair. Suddenly, everything about the way his daughter looked began to make sense. “We always wondered why she looked so serious and never seemed to smile,” John said. “I’ve always called her our ‘Serious Little Italian Princess.’”
“I used to say, ‘Why won’t you smile? I know you’re happy,’” Aileen chimed in, kissing Megan’s cheek. “To think it was just that she couldn’t, at least not without a lot of effort.”
“But here’s the really good news,” Slonim interjected. “I think there’s a reasonable chance she doesn’t have the classical form of Pompe or she wouldn’t be this strong. I think she’s one of those rare kids who have a hybrid form, between the classical and juvenile form. I’m calling it nonclassical infantile. I know that’s a lot of words, but what it means is that you may have a little more time. Not much, but a little bit. With the right diet and nutrition, she could maintain her strength for some time. Many of these children live to be maybe five years old.”
