by Geeta Anand
* * *
A week later, John flew to Amsterdam. Aside from his travels in the Navy, he had made only one trip out of the country—a week’s vacation in Italy, given to them by Aileen’s parents right after he graduated from law school. It had been easy to get around because he spoke some Italian, but he had never been to a country where he didn’t speak the language.
To his relief, virtually everyone in Holland spoke English. Pharming sent a small Mercedes to his hotel to pick him up. As a lover of cars, John was impressed—until he noticed that every cab they passed was also a Mercedes. The driver headed out into the countryside on an hour-long drive south past farms, each with a windmill and carpets of farmland.
Then the car pulled into the driveway of a concrete building with a small sign bearing Pharming’s name.
“I’m so sorry to hear about Patrick,” said Moolhuizen, a tall, bespectacled man about John’s age, as they sat down in his office. He said Pharming planned to file paperwork within the next month seeking government approval to start clinical trials in Europe and the United States. The preclinical trials, done in animals, had already been completed.3
“The results are brilliant,” he said, handing John two eight-by-eleven glossy white pictures showing microscopic photographs of tissue samples stained purple and dark pink.
“This first picture is the muscle fibers of a mouse with Pompe disease before receiving Pharming’s treatment enzyme,” he explained. “The big purple pools that fill most of the page are glycogen that has overrun the muscle. In the second picture, after the mouse has been treated with our enzyme, see how the purple pools have receded into small circles.”
John, looking from one picture to the next, saw that the smaller purple pools had been replaced with reddish strands. “Those are healthy muscle fibers,” Moolhuizen said, pointing at the ribbon-like swirls.
John looked up from the pictures, smiling. “When do you think you’ll be starting clinical trials?”
“If all goes well, very soon,” Moolhuizen said. “We are planning to begin in the next few months. We have only a small amount of enzyme, so the first patients to be treated will be babies under a year old who need less of the enzyme. We want to treat everyone, but we just don’t have enough of the enzyme.”
John’s smile disappeared as he absorbed what Moolhuizen had just said. If the trial was only for babies younger than a year old, that meant that Megan, now one and a half, would not qualify to participate.
Before he could protest, Moolhuizen was telling him the two test tubes held upright in a small wooden stand on his desk were samples of the company’s enzyme treatment.
“Take a look,” he said, handing one of the tubes to John.
The phone rang, and Moolhuizen picked it up, swiveling his chair away. John held the test tube, staring at the clear liquid in the bottom, overwhelmed at the thought that he was holding the substance that would save his children’s lives.
He looked up at Moolhuizen, who was still engrossed in his telephone conversation. Suddenly, the impulse to slide the test tube casually into his pocket overwhelmed him. If he stuffed one in his pocket, would Moolhuizen notice? Or maybe he should take both—one for Megan and one for Patick. The room seemed suddenly too hot, and his tie and jacket too tight.
But almost immediately, reason returned to him, and he remembered reading that the enzyme wasn’t a one-shot cure. Patients needed to be given the enzyme in infusions every few weeks, probably for a lifetime. He might be able to steal a couple of vials, but where would he get the next dose? He reached over and stuck the test tube back in the holder.
As Moolhuizen finished his conversation and put the phone down, John’s mind took another leap. What if the foundation he was going to start paid for a clinical trial in older children, like Megan, with the nonclassical form of the disease? That would ensure that there was a trial for Megan to get treatment.
“At the foundation, we’re close to raising a million dollars for research,” he said. The words slipped out of him without hesitation. “We’d be willing to help fund a clinical trial in children with the nonclassical form, children who are a little bit older.” He hadn’t, of course, raised a cent yet. But as with his letter telling Moolhuizen about the new foundation, John felt no guilt as he described the results of fund-raising he hadn’t yet done. He was certain now that he’d said the words that he would go home and begin fund-raising, although he wasn’t sure how he would raise a million bucks—it seemed like an enormous, almost mythic amount of money. But he pushed the thought to the back of his mind; he would figure that out later.
“I’ll talk to my people here about that,” Moolhuizen replied, his eyes lighting up.
Later that afternoon, a car drove Moolhuizen and John south toward Geel, Belgium, where Pharming was building a new manufacturing plant to make the Pompe enzyme. After a long drive, they pulled up to an industrial park where Pharming occupied the second floor of a sleek building. Moolhuizen led John inside to a sterile changing area, and helped him pull on a white cotton jumpsuit, booties, and a shower cap. Moolhuizen covered himself in the same getup. It was the kind of gear that brought to mind the sterile laboratories in movies where lifesaving medicines and vaccines were made—laboratories just like the one he stood in now. Finally, John thought, he was entering the world where his children’s medicine was being created, and becoming an insider like Randall House.
Moolhuizen led him through one fluorescent-lit room after another, filled with metal tables covered with laboratory equipment. Then the two men entered a room with a freezer. Moolhuizen opened it and pointed to a block of frozen milk about the size of John’s microwave oven at home. Moolhuizen said it was taken from the thousands of rabbits that his company milked every Monday. It would be thawed and purified to remove the acid alpha-glucosidase enzyme.
“The bodies of animals and humans work using the same system of chemical messengers, called enzymes,” Moolhuizen explained. “But you can’t treat humans missing the acid alpha-glucosidase enzyme simply by removing it from rabbits and injecting it into humans.”
The rabbit enzyme, Moolhuizen continued, was different enough that the human body would identify it as a foreign substance and mount an immune response. So in each of the rabbits, scientists had added the human gene responsible for making acid alpha-glucosidase, so that the rabbits made predominantly human acid alpha-glucosidase. He said Pharming would have preferred to make the enzyme in cows because they’re easier to milk, but they also take longer to mature. The scientists chose rabbits because they mature and multiply so quickly.
In another room, Moolhuizen showed John a big, winding glass-and-metal apparatus that he said was the purification system where the rabbit milk was slowly heated and evaporated so that only the enzyme remained. The process, from milking to purifying out the enzyme, took three days.
After they had changed back out of their white jumpsuits, Moolhuizen led John outside through a muddy field to a fifty-thousand-square-foot concrete slab surrounded by construction trailers. Standing in the middle of the slab, gesturing to one side, he said that half of the building would be used to house ten thousand rabbits. The other side would hold the laboratories, freezers, and purification equipment. Within six months, he said, the building would be finished and, soon after, Pharming would have enough enzyme to supply the world’s Pompe patients.
Moolhuizen led John into one of the construction trailers to meet his boss, Rein Strijker, managing director of Pharming’s Belgium operations. Strijker, wearing a dark suit and red tie, sat at a chair in front of a long, gleaming wooden conference table. After the introductions and handshakes, he leaned his chair back and asked, “So, Mr. Crowley, how can I be of assistance?”
“I understand Pharming intends to begin a clinical trial soon but only in infants,” John said eagerly. “I run a family foundation and I am willing to fund a trial in older children with the nonclassical form of the disease.”
Strijker sat up in his seat and
said, “That would be of interest to us. How much money have you raised so far?”
“I have commitments for several hundred thousand dollars,” John said, nodding rapidly, hoping he sounded convincing. “Within six months, I expect to have a lot more. My target is $1 million.”
Strijker sat back and said, “Well, that’s very interesting, John. Let’s speak again when you reach your target.”4
7
Megan
Fall 1998
Princeton, New Jersey; Long Branch, New Jersey; Mountainside, New Jersey
John was back at his desk at Bristol-Myers in the early evening of Monday, September 14, when Aileen called. Megan was breathing heavily, and a pediatrician had said she should go to the emergency room. John promised to meet her there.
He had returned from the Netherlands to a hectic schedule at Bristol-Myers. He was absorbing volumes of information on a group of antibiotics, antianxiety medicines, and antidepressants, which he played a major role in marketing. He had flown to San Diego for a meeting of the company’s regional marketing directors, where he proposed a standardized way to write their business plans for next year. The directors, most much older than he and with a lot more experience in the pharmaceutical industry, received his proposal with skepticism. But his boss, Brian Markison, had embraced the plan and put John in charge of implementing it. It was the most immersed in work that John had felt in a long time. It would be a challenge getting all of those sales and marketing directors to change the way they operated. The deadline was a little tight, but not overwhelming—just enough to get his adrenaline going. By September 30, he needed to pull all of the regional plans together into a single comprehensive proposal for the pharmaceutical business.1
John climbed into his old Volvo sedan and drove east on Route 195 toward Monmouth Medical Center. It would take an hour to get there in this old car that couldn’t drive over sixty miles an hour without rattling. Megan had had a cold all weekend, but it hadn’t seemed like anything serious. Was their pediatrician overreacting?
As John rolled down the window, he remembered that he hadn’t yet filled out the forms to start the Children’s Pompe Foundation. Besides his job, he’d been absorbed in the paperwork involved with buying the house he and Aileen had finally settled on, a four-bedroom colonial on a cul-de-sac in a new development in Pennington, a town adjacent to Princeton. He couldn’t afford to delay any longer with the foundation papers. As had happened today, a health problem could erupt with Megan at any time. He needed to get his foundation going so Megan could get into a clinical trial before she got really sick. As soon as he got home tonight, he vowed, he would get the forms finished.
He found Megan on an exam table in the emergency room, a big blue bow in her hair. She saw her dad and began to cry, pointing at her left big toe, to which a clip had been attached for measuring the level of oxygen in her blood. It pinched and she wanted it off. A doctor came in and read the oxygen level. He said it was 20 percent below normal. He carried an x-ray in one hand that he clipped onto a fluorescent-lit screen in the corner. “Your daughter has pneumonia,” he said, pointing to a darkish area in the picture of her lungs.
John and Aileen looked across the room at one another. They knew pneumonia was dangerous for any child, and it could only be worse for a child with a muscle-weakening disease. “As a precautionary measure, I would recommend we admit her,” the doctor said.
Within hours, Megan was settled into a room on the pediatric floor. A small tube under her nose brought a steady stream of oxygen, easing her breathing. Under her blue pajamas, three heart monitors were taped to her chest. A nurse had attached an IV tube to the top of her left hand. After screaming with each stab of the needle, she was now calmly sitting up in bed watching Barney on TV.
That night, and for the next three nights, Aileen slept on the pull-out chair in Megan’s room. By Thursday, three days after she was admitted, Megan seemed better, and her doctor suggested discharging her with a tank of oxygen to support her breathing for another couple of days. But by 5 p.m., the hospital still didn’t have the insurance company’s approval to pay for the oxygen tank for home use, and her doctor delayed releasing her for another day. John volunteered to spend Friday night at the hospital.
Megan fell asleep early that evening, and John settled into the chair to read. He was in the middle of a Tom Clancy book—Executive Orders—about a terrorist crashing a jetliner into the Capitol and killing the president. John carried a book with him wherever he went, mostly action novels, war stories, or history. In a few minutes, he grew too tired to read further. He switched on the TV to watch 20/20, and then drifted off to sleep.
All through the night, beeping awakened him. Every time Megan moved, the heart monitor seemed to go off. At about 4:30 a.m., he heard beeping again, and then louder alarms. He sat up and looked in Megan’s direction. She was half-seated, her arms waving. John jumped up to her bedside and saw she had vomited and was choking. On the monitors, the numbers showed that her heart rate was racing and her oxygen saturation plunging. He tried in vain to find the call button, and then ran into the dark hallway, shouting, “Help, help! Is anyone there? Please help!”
Megan’s room was in the middle of the pediatric floor, about six doors down from the nursing station. In a few seconds, a nurse came into the room, looked at Megan—now unconscious—and ran back into the hallway screaming, “Somebody help! I need help!”
Several other nurses, an intern, and the pediatric resident appeared in quick succession. The resident, a slight Asian-American woman, stuck a finger into Megan’s throat, trying to clear her airway, but the little girl still didn’t breathe. The resident put a mask over Megan’s face and began to squeeze the Ambu bag (a self-reinflating bag used during resuscitation), to force air into the little girl’s lungs.
“Let’s get her to the PICU,” she snapped. The medical team and John pushed Megan’s bed down the hallway as the resident ran beside the bed, squeezing the Ambu bag continuously to keep her breathing. The wheels screeched loudly, drawing black marks all the way down the hallway from Megan’s room to the pediatric intensive care unit. In their haste, the team had forgotten to unlock the wheels. Megan remained unconscious, her face gray and her lips blue.
The PICU was a big room with a central nursing station and two beds on each side. It was empty. A nurse lifted Megan onto the first bed on the right, and the resident directed the other nurses to give her one shot after another. On the heart monitor, John could see that Megan’s heart was racing and slowing and racing and slowing.
“Call Dr. Hofley,” the resident said to one of the nurses as she continued to pump the Ambu.
John wanted to call Aileen, but he didn’t dare leave Megan’s bedside. For the next half hour, the nurses and resident struggled to stabilize Megan’s heart and breathing. John stood a few feet back from Megan’s bed, silently praying that she wouldn’t die. He thought about how she had been fine the four nights Aileen stayed with her. Would Aileen blame him for not being attentive enough to prevent this from happening on the one night he was in charge? How could this even be happening when the hospital had been ready to discharge her the day before?
Finally, Dr. Marc Hofley appeared at the bedside. “Tell me what’s going on,” he said with quiet authority. The faces of the resident and nurses instantly calmed. Hofley was a pediatrician with specialty training in pediatric critical care medicine, and he oversaw the children’s intensive care units at the hospital. With short brown hair and small square glasses, he looked to be John’s age and stood not an inch taller, but the respect he commanded was evident from the second he walked into the room.2
“We need to intubate her,” he said, indicating that they needed to put a breathing tube down Megan’s throat. The resident and nurses had tried unsuccessfully to intubate Megan several times before he arrived.
Then Hofley noticed John standing in the corner and came over to him. “I’m going to need to ask you to leave while we intubate her and
put in some special lines,” he said kindly. John nodded, feeling relief that a doctor who seemed so capable had arrived. He desperately wanted to call Aileen.
From the pay phone outside the PICU, John telephoned Aileen’s parents’ house. Aileen’s dad, Marty, who was preparing to go golfing, picked up.
“Dad, we’ve got a real problem here,” John said, his voice strained. He told Marty what had happened. “I don’t know if she’s going to make it,” John finished. Marty didn’t ask any questions. He would wake Aileen and drive her over, he said.
John positioned himself outside the doors of the PICU, peeking in the small window. Megan, still surrounded by nurses, remained on the bed, naked and unconscious, a tube or monitor attached to every limb. “Please, please, Megan, don’t die,” he said softly. “C’mon, Megs, don’t let go.” He felt dizzy and nauseous, and realized he was sweating. He took off his sweater and set it on a chair, and began to pace up and down the corridor, empty except for him.
When he looked in the window again, the nurses were still rushing around Megan. He noticed that she filled only the top quarter of the bed. Was she in pain? Was she suffering? It was unbearable to think of anything hurting his tiny daughter. “Dear God, please don’t let her suffer,” he began to pray, his nose pressed against the window. He remembered the certainty with which Dr. Slonim had described how quickly she would weaken over the next year. Maybe it was better that she should die now rather than endure more suffering.
It was the hardest thing he’d ever said, but he forced the words through his numbed lips: “God, please don’t let her suffer anymore. If death is inevitable, let it come.”
With a start, he realized he couldn’t see Megan any longer. He was crying so hard the window had fogged. He wiped the window with a handkerchief and began pacing the corridor again.
Even if death was best for Megan, how would Aileen ever endure the loss? As husband and father, as the parent who was there, he’d have to be the one to tell her. What could he say that wouldn’t break her already battered heart? Should he say, “Honey, Megan died this morning—there was nothing you, or anyone, could have done”? Just thinking the words made him ache with misery. Maybe he would say, “Honey, Megan loved you very much, and you did everything you could, and now she’s at peace.” Would he even be able to get a single word out when he saw Aileen’s face?
