by Geeta Anand
No sooner did Aileen and John arrive at the rehabilitation hospital with Megan than they started feeling less sorry for her. Many of the children had no visitors, and they cried and reached out to John and Aileen. Aileen didn’t let herself go over—she knew it would be impossible to extricate herself. But John missed the lesson on how to bathe Megan without getting her breathing tubes wet because he was holding the child in the next bed, who screamed every time he was put down.
At the rehab hospital, the day of the test of their medical skills arrived. John had volunteered to go first. A nurse pulled apart the Velcro strap that held Megan’s tracheotomy in place so that it fell out of her throat. John’s job was to show he could put it back in. Megan began crying and pushing at the tube. Without it, she couldn’t breathe. John grabbed her hands with one of his while he tried to push the tube back in with his other hand. He struggled, unable to slide the tube in, watching Megan’s face grow pale and more frantic. He looked helplessly at the nurse.
“I can do it,” Aileen said, jumping up. “Megan, honey, Mommy’s going to put it right back in.” She took the tube from John’s hand and gently slid it into the opening in Megan’s neck. On the next try, John, too, was able to get the tube back in. The nurse looked at both of them, trying to decide if what she had seen was enough to save the child’s life the next time the tube came out. Finally, she nodded and scrawled her signature on the form indicating that the Crowleys were capable of keeping Megan alive.
Now, finally, they were ready to take Megan home.
8
The Conference
Fall 1998
Pennington, New Jersey; Bethesda, Maryland
Life had changed dramatically. John and Aileen’s new home was like a hospital. Nurses and therapists came and went all day and night through the unlocked front door. The keys to their house got lost, and they didn’t even bother replacing them. Meanwhile, John spent every evening either on the Internet or phoning the IRS to get his foundation papers approved.
Day and night, the whooshing of Megan’s ventilator filled the house. It pumped twenty-two breaths a minute into her weak lungs, swishing louder or softer, faster or slower, depending on the settings. The alarm sounded dozens of times each day, signaling that Megan’s airflow might be disrupted from a tangle or disconnection in the long plastic tube that connected her tracheotomy to her ventilator. If she arched her back or made some sudden movement, the tracheotomy tube would pop out of her neck and Aileen or John would race over to thread it back in. If she pulled on the tubing that connected the tracheotomy to the ventilator, or if John Jr. tripped over it, one end or the other would come unplugged. The worst were the mucus plugs that built up every so often in the tracheotomy tube, blocking her airflow, presenting an immediate, life-threatening emergency.
At first, both John and Aileen would both sprint to Megan’s side when a beep sounded, but they soon learned to wait until six or eight beeps had elapsed and jump in only if it was apparent the nurse couldn’t immediately find the problem and correct it. For her part, Megan grew accustomed to at least one crisis with her breathing every day. Her solemn dark eyes trained on the face of John or Aileen, she remained calm unless she detected concern—a raised voice, a frown—as they tried to correct the problem. Then the little girl would panic and grab and push at her tracheotomy, making it much harder to thread back into her neck. But after a burst of crying as soon as her airflow was restored, Megan would begin another game of Barbies.
In November, John learned that sixty-five Pompe disease researchers and doctors from around the world were planning to gather at the National Institutes of Health (NIH) in Bethesda, Maryland, for a conference. Randall and Marylyn House and their Acid Maltase Deficiency Association were organizing and cosponsoring the third annual meeting of Pompe researchers. Concerned about the lack of communication and cooperation among researchers working on the disease, the couple had sponsored the first Pompe disease meeting in their hometown of San Antonio two years earlier. At the Hyatt hotel downtown, about 30 scientists working on Pompe and related disorders met for the first time. They had been competing with one another on scientific milestones for years but had never had occasion to gather and share information. Marylyn presented a detailed case study—the best researchers would later say that they had ever heard—of a juvenile with Pompe: her own daughter, Tiffany. With the smiley, pony-tailed thirteen-year-old, her spine already so deeply curved with scoliosis that she had trouble walking, a poignant presence at the meeting, the researchers felt inspired to work collaboratively, with patients in mind rather than research papers. They went home to their labs and began to exchange ideas, DNA samples, and mice. For the next decade, Pompe researchers would talk about that first meeting as a life-changing, work-altering experience, and credit the Houses for bringing them together.1
Looking for any new source of information and hope, John called Dr. Slonim on the phone and asked how he could get himself invited to Randall’s next meeting. By now, Slonim had grown fond of John. He had come to relish his frequent phone calls, enjoying his sense of humor and appreciating his urgency. “It’s important for John to get involved not just for his children’s sake, but also for himself,” he had told his nurse Linda. Slonim encouraged John to attend the meeting and told him to call Randall to get his name added to the list of invitees.
John hung up and immediately dialed Randall at his office. He knew Randall hadn’t liked his plan to start his own foundation, but he hoped he had moved past that.2
“Hello, John, how are you?” Randall said, warmly.
“Fine, Randall,” John said, feeling encouraged.
“How are Megan and Patrick?” Randall asked.
“Well, quite frankly, Randall, things could be better. We’ve had a pretty rough time,” John said. “Megan got pneumonia and then a staph infection in the hospital. She was in the hospital for six weeks, but we finally have her home.”
“I’m terribly sorry to hear that,” Randall said, and John believed him. Randall was one of the few people in the world who knew the terror of living every day under the threat of losing your child. He took a deep breath and plunged into his request.
“Hey, Randall, I heard about your research meeting coming up in Bethesda and I wondered if I could attend.”
“Well now, John, the meeting is only for scientists,” Randall said, the warmth gone. “We’re not inviting any parents.”
“But I need to meet these doctors,” John pushed. “I need to tell them about Megan and Patrick’s cases. I need to find out about any new research going on. I’m running out of time.”
“If we invite you, other parents will want to come,” Randall said. “They would interrupt the flow of scientific discussion. The goal of this meeting is to promote understanding and cooperation among the scientists to get a cure for this disease as quickly as possible. This is not a parents’ meeting.”
“What do you mean, Randall? I have to be there,” John pressed, his tone pleading.
“And what I’m saying is you cannot be at this conference,” Randall said firmly, bringing the conversation to a quick close.
John sat at his desk, shocked. He called back Slonim and told him what had happened. Slonim phoned Dr. Paul Plotz, a scientist at the National Institutes of Health, which was cosponsoring the meeting, and told him about John’s desire to attend. Plotz said nobody could be barred from a meeting at the NIH—least of all a parent—and he agreed to telephone Randall and tell him so.3
A few days later, the phone rang at John’s office. Marylyn House was on the phone with her lawyer.4
“Just know you may come to the conference, but you are not welcome,” she said, fuming. “It’s not me and my husband who don’t want you there, it’s the doctors. We’re so close to getting a treatment. If you get involved, you’re going to screw it all up.
“We’re going to set the ground rules, though, and they’re going to be very strict. You have to sit in the back row, you can’t talk or as
k questions, you’re not even to talk to doctors during breaks.”
Then the lawyer told John he would need to sign a confidentiality disclosure agreeing not to reveal any scientific secrets he learned.
“That’s fine,” John said. He hated Marylyn’s angry, lecturing tone, which made him feel like a child, but he knew he had won this round. He would sign whatever paper they put in front of him. In the years ahead, it would prove to be a crucial victory.
On December 2, John checked into the Hyatt in Bethesda, Maryland. He had arranged to have a drink that night with Gerben Moolhuizen, the Pompe disease coordinator at Pharming with whom he had spent the day in the Netherlands a few months earlier. They met at the hotel bar.5
Moolhuizen, ever gracious, asked John how his children were doing. John told Moolhuizen about Megan’s health scares that fall.
“What about the boy?” Moolhuizen asked.
“Patrick is still healthy, but I see some signs of weakening. We all wish we weren’t noticing it, but the little guy is starting to have a bit of trouble swallowing and will probably need a gastrostomy.”
The two men ordered a round of beers. As they took their first sips, John looked directly into Moolhuizen’s eyes and made his first direct plea on his children’s behalf.
“Gerben, I need to get this drug to my kids really soon,” he said.
“John, I’m trying,” Moolhuizen said, “but production is very, very tough. It’s not as simple as we thought to get this enzyme out of the rabbits.”
“How are the clinical trials coming?” John asked.
“We plan to start very soon the trial in Europe in infants,” Moolhuizen said.
“What about the U.S. trial?” John prodded.
“That may be some time,” Moolhuizen said, looking down. He said that Pharming’s new production plant in Geel, Belgium, would need to pass an FDA inspection before the enzyme treatment could be infused into patients in the United States. And even if Pharming got the go-ahead from the FDA, the company wouldn’t be able to produce enough drug for a second trial for some time.
“What about Genzyme?” John asked. Surely Pharming’s partner, with its deep pockets and manufacturing expertise, could solve these problems.
“The partnership isn’t going well,” Moolhuizen said. “Genzyme is not able to help us with the problems with the rabbits.” They were difficult to milk, and the milk contained less and less enzyme as they aged, he said. It was proving hard to get enough enzyme from the herd of rabbits to treat more than a handful of people.
John took a swig of beer, letting the disappointment sink in. After reading about the Genzyme partnership, visiting the Netherlands, and touring Pharming’s production facilities, he had come to see the company’s clinical trials as a life raft for his children. Now, in a moment of candor, Moolhuizen was pulling it away from him. John could raise all the money in the world to fund a clinical trial, but if the companies couldn’t make enough of the drug, he was nowhere.6
The campus of NIH buildings was so vast that it took John an hour and a half the next morning to find the right meeting hall. When he arrived, the meeting was already under way in a building called the Cloister, a former abbey. John walked through a long lecture hall with vaulted ceilings, and into an adjoining room where about sixty people sat listening intently. He saw the back of Dr. Slonim’s balding head in one of the rear seats and slid into a vacant chair beside him. Slonim reached his right arm over and patted the younger man on the back, as if sensing John’s frustration at being so late and his awkwardness at having forced his way into the meeting. At the podium, a scientist John didn’t recognize was talking about experiments in his lab.7
John sat quietly, trying to follow. He soon realized he didn’t understand anything the man was saying. He tried to remember when he had taken his last biology class. It was in tenth grade at Bergen Catholic High School and was taught by the school’s assistant wrestling coach. He’d have to learn a lot more science if he was going to run a research foundation.
As the day progressed, speaker after speaker whose names he knew only from the Internet rose to talk about their work. It was the ultimate crash course in the molecular biology of Pompe disease. Arnold Reuser, the pioneering Dutch scientist who had worked on Pompe disease for most of his life, came to the podium. Wiry, with frizzy white hair and a flair for the dramatic, Reuser put up one slide after another that looked similar to the ones John had seen in the Netherlands a few months earlier—mouse tissue replete with big purple pools of glycogen and only a few red strands of surviving muscle fiber, and subsequent slides showing a dramatic shrinking of the purple areas after treatment.8
“Look how much our enzyme has reduced the glycogen pools,” Reuser said. “This is very exciting data for everyone in this field.”
John liked Reuser’s passion and optimism.
Dr. Chen, his children’s own doctor, a soft-spoken presenter, described his experiments giving the enzyme he had grown in CHO cells to Japanese quails, one of the few species of animals known to naturally develop Pompe disease. He showed photographs of the quails that could only hop around before being treated, and the one that was flying after a few weeks of injections with his enzyme. One day, John thought, these doctors and scientists would be making presentations showing slides of Megan and Patrick’s muscle tissues cleared of glycogen after receiving the treatment enzyme. Instead of quails flying, the videos would show his children walking.9
Dr. Frank Martiniuk, a research associate at New York University, advocated gene therapy as the solution. He reported using a “gene gun” to insert the gene that codes for the Pompe enzyme into mice. The muscle cells that received the gene began to produce the Pompe enzyme, acid alpha-glucosidase. The big challenge was figuring out how to get the gene into all the muscle cells of the body.10
The final presentation the next day unsettled him. A surly, white-bearded researcher suggested that neither Chen’s nor Reuser’s enzymes would work. The physician-researcher’s name was Dr. William Canfield and he was a biochemist from the University of Oklahoma.11
“It’s not enough to make the enzyme correctly,” Canfield said. “For the enzyme to be taken up properly, you need the correct glycosylation.”
John had never heard the word, and he didn’t think anyone else at the conference had used it.
“What’s glycosylation?” John asked Slonim in a whisper..
“He’s talking about the importance of carbohydrate and phosphate structures attached to the enzyme, where everyone else at the meeting has been focused on the enzyme alone,” Slonim whispered in reply.
Canfield said neither the enzyme made in CHO cells nor rabbit milk had the right attachments of carbohydrates and phosphates to be transported to the lysosomes of muscle cells, where they were needed. He had spent a decade in his lab figuring out how to make the right attachments, and he believed he had finally worked it out.
John noticed researchers associated with Pharming and Duke shaking their heads in disagreement in the rows ahead of him. They were mostly molecular biologists, and most of them didn’t know Canfield, a biochemist. And they clearly did not agree with him. John found himself wanting to dismiss Canfield, too.
“Is this guy for real?” John whispered, hoping Slonim would have something derogatory to say about this researcher’s negative pronouncements. Everything Canfield was saying implied that Pharming and Genzyme’s treatments were never going to be effective.
“Nina and Paul think he’s onto something,” Slonim said, using the first names of the NIH researchers, Dr. Nina Raben and Dr. Paul Plotz. “They invited him to attend.”
John said nothing. If Canfield was right, hope was even further off than it had seemed before.
When the speakers were finished, John saw Canfield standing uncertainly amid a group of scientists in the back of the room. As he had done repeatedly over the two-day meeting, Dr. Slonim ushered John over and introduced him as the head of the newly formed Children’s Pompe Foundat
ion. The two men shook hands.12
Randall stepped up to the podium to invite the researchers to be his guests for dinner. He had arranged for a bus to pick up everyone outside the Hyatt at 7 P.M. and take them to a French restaurant called La Miche, where he had made reservations.
John, standing quietly beside Slonim as he chatted with the other scientists, knew that the invitation probably didn’t apply to him. But if he could somehow push his way into the event, he thought, he would have a chance to get to know a few more researchers. Perhaps he would even talk further with Randall and mend relations.
Back at the hotel, John dressed for dinner, putting a blue blazer over khakis and a blue dress shirt. As he waited in the lobby, he could see Randall outside, beside a school bus. The researchers had formed a line to get on the bus. John waited inside until most of the group had climbed past Randall before appearing at the end of the line.
“Hi Randall,” he said as his turn came, smiling and extending a hand.13
“Oh, no, you’re not coming to this dinner,” Randall said, shaking his head, crossing his arms, and standing in the entrance. “It’s my party and you’re not invited.”
John looked up at Randall. At over six feet, his gold Rolex on his arm, he was everything John wasn’t—big, rich, and experienced in the business and Pompe worlds. He couldn’t help the wave of embarrassment that washed over him, feeling indescribably small and poor and young.
“That’s fine, Randall,” John said, turning to leave. “That’s fine.”
The bus with all the other conference attendees pulled out of the driveway. John rode the elevator upstairs, staring at his shoes. As he waited for his bow-tie pasta in marinara sauce to be delivered to his room, he sat on the bed, his head in his hands, thinking of his mother. Even as she’d quoted President Kennedy and other men she admired for advocating for justice and equal opportunity, she had always added her own dose of realism, telling him you were nowhere in the world without money.
