The Cure

by Geeta Anand

  So John set about trying to persuade Canfield that he had a product ready to use in animal testing—the Pompe enzyme made with bovine PTase.

  “Bill, I’m not advocating using the bovine PTase in humans. I’m just saying we should use the stuff for our animal testing. We’re going to need the money soon. These guys at Neose are just looking for an excuse to invest more. Why not use the stuff you have for the animal experiments so we get proof-of-concept data?”

  “It’s a waste of time,” Canfield replied. “If we can’t make human PTase, we’re done. Why bother with animal experiments using an enzyme we would never put into humans? I don’t see the point. If we can’t make human PTase, we have nothing.”

  “It’s not a waste of time, Bill. It’s just a way to prove to Neose that the enzyme works. It’s a proof of concept,” said John. “We get the money we need. When you have the human PTase, we’ll do the experiments over.”

  Reluctantly, Canfield handed over a few vials of his enzyme, but he said he wasn’t going to do the animal testing, nor were any of his scientists, who were focused on what he viewed as the make-or-break human PTase challenge.

  John’s excitement at having won the argument diminished momentarily when he realized he didn’t know who would perform the experiments. Seeing John’s distress, McKinney, eager to please, volunteered to do the animal experiments. “I used to work as an emergency room tech,” he assured his young CEO.

  John patted him on the back, thrilled. “If you can inject people, you can surely inject a mouse,” he chuckled. The complete absurdity of their attempting to conduct animal experiments would become apparent to them only later, when they learned that these tests must be done in exacting detail to have any credibility whatsoever in the scientific world, let alone with the FDA.

  One afternoon in the late fall of 2000, John and McKinney donned white lab coats over their pin-striped suits and stepped into the lab across from Canfield’s office. McKinney pulled on a pair of surgical gloves and filled several tiny syringes full of enzyme. John watched from a few feet away as McKinney grabbed three weakly wriggling mice, one by one, and injected their tails.9

  “Not sure I hit the vein,” McKinney said, holding one of the black-tailed mice up to the light. “It’s hard to see. This book I read says we’re aiming for the tail vein but it’s hard to see the vein ’cause the mouse is brown. I’ll give this mouse another shot of enzyme just to be sure we got the stuff in the right place.”

  “Is it going okay?” John asked after the unplanned second dose.

  “Oh yes,” McKinney said, reassuringly. “I saw some drawback that time. Definitely got the tail vein. This bad boy got himself some enzyme flowing in his blood.”

  Every week over the next month, McKinney gave the mice another injection or two of enzyme, John looking on nervously. Canfield, shaking his head each time he saw the two men enter the lab, pointedly refused to even watch, let alone participate.

  At the end of the month, McKinney killed each of the mice and sliced out their organs. He performed what is known as an enzyme activity test by grinding up the organs and measuring the level of Pompe enzyme. If the mice showed any amount of enzyme in their tissue, he explained to John, it meant the enzyme had been taken in.

  To John’s delight, McKinney reported back that the experiments showed Canfield’s enzyme had been transported into the organs of all three mice. McKinney charted the results on his laptop and showed them to John. He pointed to a dot on a graph that represented tissue taken from an untreated mouse with Pompe disease, which contained less than 1 percent of the enzyme level of a normal animal. Three other dots in different places, but all higher on the graph, represented the enzyme levels measured in the organs of treated mice. The top performing mouse had 25 percent of the enzyme level found in a healthy animal.

  “The results are mixed,” McKinney told John. “There’s some good data, some we’ve got to work on.”

  “What do you mean?” John said.

  “I mean the results aren’t perfect, but they are promising—I see some very promising signals,” McKinney said.

  John thought it was time to visit Neose. Even if the experiments weren’t perfect, from what he could tell, the results showed that the mice with Pompe disease had taken up Canfield’s enzyme. Surely they would serve as a “proof of concept.” It was worth a try, anyway, to get Neose on the clock to invest more and share in the future costs of drug development.

  John and McKinney knocked on Canfield’s door and showed him the results. Canfield, stroking his trim beard, shook his head as he looked at McKinney’s chart.

  “This is not compelling,” he said.

  “C’mon, Bill,” John said. “We’re not presenting at a scientific conference. We just want to show the guys at Neose that we’re making progress. This doesn’t have to be conclusive evidence.”

  Canfield shrugged and left the room to return to the lab where his scientists awaited his guidance on the vitally important PTase experiments.

  John decided Canfield was too much of a skeptic. John’s own business school training had taught him not to wait for the perfect result, but to forge ahead with the best information you had. John called Sherrill Neff, the chief operating officer of Neose, and set up a meeting for the next week.

  The next day, Canfield made one final argument against presenting to Neose.

  “I can’t make the trip to Pennsylvania,” he said. He was still technically employed by the University of Oklahoma, and as a physician, he was required to be on call for one month each year at the university hospital. His tour of duty was this month, December. “No problem, Doc,” John said in his chipper way. “Tony and I will present the data.”

  As they pulled up to the Neose offices outside Philadelphia on December 14, John stared at the big white letters on the outside of the warehouse spelling the company name and suddenly felt nervous. He remembered the last time he’d visited here, with Canfield, and the rapid-fire science questions that had stumped even the brilliant scientist.

  Minutes later, he and McKinney were seated side by side in the conference room across from Roth, the scientist and chief executive who had grilled Canfield the previous time. By Roth’s side sat Marjorie Hurley, the tough head of regulatory affairs, and farther down the table, a Neose physician named David Zopf, and Neff, the chief operating officer.

  McKinney, overcome with a sudden sense of impending disaster, whispered, “John, maybe you should present the results.” John, voice adamant even in a whisper, insisted McKinney do the job.

  “You’re the one with the science background,” John hissed back. McKinney had an undergraduate degree in microbiology from the University of Oklahoma. Clearing his throat, John began to make the introduction.10

  “Well, we’re here because we have some early but, we think, very compelling evidence that our enzyme works in mice,” he said, sounding assured as he always did in public. “We believe we have the proof-of-concept animal study here. Tony McKinney, our chief of drug development, will present the results.”

  McKinney smiled weakly and directed the group to look at the graph on his PowerPoint presentation, on which he’d plotted the enzyme activity levels in the three treated mice.

  “Why are your results so variable?” Roth asked. John focused for the first time on the fact that the enzyme activity levels in the three mice differed from one another by five or ten percentage points, realizing he was so far out of his league that he hadn’t even known this might be a problem. McKinney had drawn a nice straight line through the middle to show the average.

  “Well, it may be due to the fact that it was hard to find the tail veins in the mice,” McKinney said. “So some may have gotten more enzyme than others.”

  Roth’s eyes widened.

  “Who performed the experiments?” he asked.

  “I did,” McKinney said.

  “What?” Hurley’s face had taken on the same pained expression John remembered from his first visit to the co
mpany in April.

  “Are you an expert in preclinical studies?” Roth demanded, incredulous, knowing full well that McKinney was not a trained scientist. In the world of science and medicine, having an undergraduate degree in microbiology was considered barely better than kindergarten. “How do you know the enzyme actually got into the tail vein?”

  “We can’t be sure, but I surmise from these readings that we got the enzyme into the tail vein,” McKinney said faintly. Beads of sweat had formed on his forehead, and his hand pointing at the screen trembled slightly.

  The questions kept coming, all or almost all of them leaving McKinney foundering for answers. John felt powerless to help him.

  Finally, incredulous, Roth shoved himself violently to his feet and shouted, “This is bullshit. Now I understand why Bill isn’t here. He doesn’t have the balls to present this crap.”

  John watched, horrified, as Roth stormed out of the meeting, just as he had after the meeting with Canfield almost eight months earlier.

  The next day, Roth phoned Canfield, demanding an explanation. Canfield was a man of few words and he grew even less verbose when under attack. He didn’t try to defend himself by explaining that he hadn’t wanted John and McKinney to present the results in the first place. Canfield, who hated direct confrontation, had been—and remained—so completely absorbed in the challenge of making human PTase that he hadn’t expended the energy questioning John and McKinney before they left to realize the level of sloppiness of their experiment. Distracted and exhausted by his own scientific problems, he had avoided the conflict, retiring to the domain in which he was most comfortable—the lab. But now he was sure the Neose chief was right, and he was furious with himself for not putting his foot down and banning John and McKinney from making the trip. As the chief scientific officer, Canfield knew any science that emanated from the company reflected on him.11

  Canfield put down the phone and sat silently in his office. Then he picked up the phone and called Doug, his lawyer and confidant.

  “I’m worried about John,” he said. “We just had a terrible mistake that could ruin us. John insisted on presenting this half-baked data to Neose. He thought that all the guys at Neose wanted was an excuse to invest. Now Neose is furious. You know, I was worried about John’s conflict of interest, and now I think it’s a problem. He’s rushing too fast and cutting too many corners.”

  “Bill, we can manage him,” came Doug’s reassuring reply. “This Neose thing sounds terrible, but we can smooth it over. I’ll talk to John.”

  “And why hasn’t he moved to Oklahoma?” Canfield continued, anger flooding his voice as he lunged into the topic he complained about frequently to Doug. “You were there, Doug, when we offered him the job and told him he had to move to Oklahoma. If he couldn’t do it, he should have said so. Now he’s gone and rented office space in New Jersey for himself on days when he isn’t here. He hasn’t said the words yet, Doug, but I’m sure he’s not moving here.”12

  “Bill, it’ll be all right, even if the guy doesn’t move,” Doug said. “I don’t see how he can take those sick kids away from all the family support back in New Jersey. John’s here almost every week, he’s working all night, he works every weekend. What does it matter where his family is?”

  “I just don’t like it,” Canfield said. “If he wasn’t going to move, he should have said so before starting. It seems like John Crowley will do almost anything and say almost anything to get a drug to his children. He just ruined my reputation with the Neose guys. They think I sent John and McKinney over there to present those results.”

  A few days later, on Christmas Eve, Neose’s Sherrill Neff called John and invited him to Pennsylvania to talk. Neff was about twenty years John’s senior, and after meeting several times, John had begun to think of him as a mentor. It had been Neff who had helped John broker the deal between the two companies following the first disastrous meeting he had attended. John knew that within Neose, Neff was the biggest champion of the partnership between the two companies. Neff saw beyond John and Canfield’s inexperience in drug development, recognizing the commercial potential of the science. Neff was a nonvoting member of the Novazyme board, but he often called John after the meetings to offer advice.

  This time, Neff seemed much more distant. He was quiet as they drove from the Neose building, only speaking once to ask if it was all right if they ate at a small sandwich shop.

  When they finally sat down with sandwiches, Neff got right to the point. “John, I’m concerned. I haven’t been around the biotechnology world long, but I’ve been around long enough,” he said, looking directly into the younger man’s eyes, his tone firm but devoid of anger. “If you’ve got a problem, you’ve got to talk to your investors and your board. You’ve got to tell them you’ve got a problem and what your proposed solution is. It’s the single best way to keep a coalition together.”

  John nodded, silent.

  “The other day, you and Tony presented your data as great. Not only was it poorly done, but it also wasn’t even good data. This business is full of people who are full of themselves and who try to spin data. If you’re not careful, you’ll quickly develop a bad reputation. You’ve got to avoid getting a reputation as a shit polisher in this business.

  “At our meeting the other day, you tried to polish the shit.”

  John took a deep breath and tried to smile. Neff had delivered his admonition in such a kind, big brotherly way that John felt it was given for his own benefit.

  “I understand,” John said, looking up at him. “We’re going to hire a director of preclinical studies to do the future studies. We’ll do it right. I’m learning.”

  A week later, at 6 p.m. on Saturday, December 31, the phone rang in John’s house. It was Canfield, characteristically short-spoken and terse.

  “Turn on your fax machine,” he said.

  “Why?” John asked.

  “Just turn on your fax. I’m sending something over.”

  John switched on the fax and stepped outside into the den to check on the kids.

  A New Year’s Eve party Aileen had organized was under way at the Crowley household. Patrick, two, was ignoring everyone from his usual perch on the left side of the couch, watching the Wiggles, a kids’ show featuring a group of young Australian men singing and dancing. Sharon was at home in New Hampshire with her family for New Year’s, but one of the children’s favorite nurses, Helen, sat by Patrick’s side, rising often to check on Megan, who was playing with two friends in the adjacent room.

  John Jr. appeared at the top of the staircase and shouted, “Where can I hide, Daddy?”

  John pointed in the direction of his bedroom, a finger over his lips. “Don’t let them hear you or they’ll know where to look.”

  John Jr. had started kindergarten that fall and had finally become easier to manage. His teacher, Laurie, who had become a close friend of Aileen’s, had persuaded her to have him tested for attention deficit hyperactivity disorder. When the diagnosis came back positive, a physician had prescribed Ritalin, and it seemed to help John Jr. He was finally able to focus long enough to play a game with his cousins.

  As John Jr. disappeared, John peeked into the adjacent room. Megan, now four years old, sat in a small chair, her ventilator at her feet, playing dolls with Angela, eight, who lived next door, and Alexa, nine, who was the kindergarten teacher Laurie’s daughter. Their parents were partying with the adults in another room.

  “Hey girls, don’t let Megan boss you around, you hear?” John teased, kissing Megan’s cheek.

  She pinned her dad with a withering stare and pointed imperiously at the “No Boys” sign written in crayon and posted on the door.

  Laughing, John went downstairs to the basement he and Aileen had just had refinished into a party room with a bar and pool table. In a glittering, low-cut top that tastefully accentuated her ample cleavage, Aileen was serving red and green Jello shots she had spent the past week mixing and freezing. It was still earl
y, but most of the guests had arrived, including John’s naval buddy Ed, Aileen’s brother Brian, sister-in-law Kim, her cousin Kevin, and his wife Lisa. In the mix were several new Novazyme employees from their Jersey office—Canfield had indeed been correct that John had decided to stay in the state. Ignoring Canfield’s anger at him for not moving to Oklahoma, John had initially rented space at an office center outside of Princeton and hired several people to work there. Not only would it have been very difficult to move his family, but John had also rightly concluded that having a second office in New Jersey made sense. He could attract talented people from the area’s enormous pool of pharmaceutical workers who would never dream of relocating to Oklahoma. Just this month, with several new hires bringing their rented space to its capacity, John had moved the office to a white, two-story colonial on Nassau Street in Princeton.

  Aileen slid a jello shot into John’s mouth. “How are the kids doing upstairs?” she asked.

  “They’re having a great time,” John said. “Megan just banished me. Oh, I almost forgot—Canfield called and said he has something to fax over. Maybe it’s a resignation letter he’s drafted on my behalf that he wants me to sign,” John said, making a joke of Canfield’s frustration with him over the Neose debacle. “Let me see if it’s arrived yet.”

  “What’s he doing for New Year’s?” Aileen called as John ran up the steps.

  “He’s still at the office,” John shouted over his shoulder.

  “Geez, doesn’t the guy ever take a break?” Aileen asked, popping a jello shot into her own mouth.

  In the study, the fax machine was spewing out a series of graphs. John stared at them, straining to understand what Canfield was trying to convey. And then it clicked. John let out a whoop of jubilation and dialed Canfield’s office line.