The Cure
Page 36
As if the demands of Amicus and family weren’t enormous enough, John took on one more role when he accepted a commission several years ago as an officer in the U.S. Navy Reserve. He has been promoted to the rank of a full lieutenant, assigned as an intelligence officer to a unit in the U.S. Special Operations Command.
“When I voluntarily resigned from the Naval Academy over seventeen years ago, I wrote in my separation letter that at some time and in some way I would again serve my country when it was needed most,” he wrote in his application. For him, after September 11, that time had come.
John’s best friend, Ed Devinney, now commanding officer of the USS Cole, swore him into the Navy Reserve on a high floor of an office building overlooking Ground Zero. John spends one weekend each month and several weeks a year away from home working on a variety of Navy intelligence projects.
When I interviewed her years ago, Dr. Nina Raben, the biochemist from the National Institutes of Health, said something about the Crowleys’ journey that I have continually found to be true. “This is a very American story,” Dr. Raben told me, having grown up in the former Soviet Union. “It’s about hope, it’s about willpower, it’s about money. It’s about a belief in happy endings.”
As human beings, we are defined at our core by how we respond to hardship. Writing about the Crowleys has taught me that there isn’t one right way, but that each person must find her own path, drawing on her own unique strength, passion, and resources. Who can say whether John’s or Aileen’s role is more important? Fueled by love, each of their journeys is tough, vital, and courageous. Knowing that each day really may be their children’s last, these parents live with abandon, throwing themselves into every birthday party, trip to Broadway, weekend in Ocean City. Knowing so intimately the tenuousness of life, they instinctively understand what most of us forget: all they really have, and all they are really pursuing, is time—time with the people they love. And so they grab onto each precious moment, cherish it, celebrate it, laugh at it, cry in it, and hope for another—even as they continue on the journey into the unknown and the unknowable that we call life.
Geeta Anand
October 2009
Timeline of Major Events
December 16, 1996 Birth of Megan Crowley.
June 5, 1997 John Crowley graduates from Harvard Business School.
March 6, 1998 Birth of Patrick Crowley.
March 13, 1998 Dr. Daniel Birnbaum diagnoses Megan with Pompe disease.
May 21, 1998 Aileen Crowley and the children move to her parents’ house in Rumson, New Jersey.
Week of July 6, 1998 Dr. Y.T. Chen calls with blood test results indicating Patrick might have Pompe disease.
July 27, 1998 John begins work at Bristol-Myers Squibb Co. as a field marketing director in neuroscience division.
Mid-August 1998 John travels to the Netherlands to meet with Pharming officials about their Pompe disease trial.
September 14, 1998 Megan is admitted to Monmouth Medical Center with pneumonia; she is later moved to the Pediatric Intensive Care Unit.
October 26, 1998 Megan is released from the rehabilitation center and family moves into new home in Pennington, New Jersey.
December 3–5, 1998 John attends National Institutes of Health conference in Bethesda, Maryland, where he first meets Dr. William Canfield.
June 3, 1999 Chen begins his first clinical trial, infusing baby John Koncel with the enzyme replacement therapy.
November 1999 John and Aileen host the Children’s Pompe Foundation fund-raiser at the Millennium Hotel in Manhattan.
April 4, 2000 John begins work with Canfield’s company, later named Novazyme.
September 12, 2000 Novazyme closes first round of financing, raising $8.3 million, with Perseus Soros, HealthCare Ventures, and Catalyst as investors.
December 14, 2000 John and Tony McKinney present the results of their “proof of concept” experiments to Neose.
December 31, 2000 Canfield successfully clones human phosphotransferase (PTase).
January 8–11, 2001 H&Q meeting in San Francisco. Neose and Perseus Soros representatives discuss the possibility of fraud at Novazyme.
January 16, 2001 Venture investors and Neose question John and Canfield about the disastrous scientific presentation made by John and McKinney on December 14.
February 8, 2001 Novazyme dedication of Lindsey Paige Easton Biologics Manufacturing Facility.
March 17–24, 2001 Crowley family participates in Megan and Patrick’s Make-A-Wish Disney trip.
April 4, 2001 John and Canfield meet with Genzyme and present Novazyme’s plans to develop a next generation Gaucher treatment.
June 18, 2001 Novazyme board decides to sell to Genzyme.
August 8, 2001 Genzyme signs definitive merger agreement to acquire Novazyme.
September 26, 2001 John begins work at Genzyme as senior vice president and head of the Pompe disease program.
January 31, 2002 Results of Genzyme’s “Mother of All Experiments” presented.
February 28, 2002 John holds Pompe Summit for Genzyme employees to meet patients.
April 1, 2002 Crowleys move to new house in Princeton.
Week of August 5, 2002 Board at Children’s Hospital of Philadelphia meets to review Dr. Hal Landy’s Sibling Study, and raises questions about John’s conflict of interest.
September 2002 John and a team of Genzyme employees meet in Rotterdam with families of Pompe patients on the Pharming enzyme.
October 4, 2002 Dr. Barry Byrne calls John to say his Institutional Review Board (IRB) has approved his revised Sibling Study trial.
October 7, 2002 Landy calls John to admonish him for submitting the application for Byrne’s study; subsequently, John drops the plan.
October 29, 2002 John and Aileen attend family visitation at funeral home for Kelsey Ann Assink in Hudsonville, MI.
December 19, 2002 John’s last day at Genzyme.
December 24, 2002 Dr. Debra-Lynn Day-Salvatore’s Christmas card arrives at the Crowley house with trial approval and a start date for the Crowley kids.
January 9, 2003 Megan and Patrick receive first infusion of Special Medicine.
Notes
Prologue
Dr. Priya Kishnani explained that the difficulty in speaking clearly for patients with Pompe disease is due to weakness in the oropharyngeal muscles, the ones involved in speech, in an interview March 30, 2006, and follow-up e-mail exchange.
Chapter 1
Barbara Valentino Crowley, in an interview on February 26, 2004.
Details here are from interviews with John, Barbara and Joe Crowley in 2004.
Interviews with Mike Ostergard, Harvard Business School classmate, on October 26, 2004; John Gordon, another former classmate, October 27, 2004; and Karl Palasz, also a former classmate, October 28, 2004.
Chapter 2
Dialogue and detail in this scene are based on the recollections of John and Aileen in interviews in 2004; Dr. Kong, in an interview on June 14, 2006, said his medical records from 1997 and 1998 were in storage and he no longer had a clear recollection of his meetings with the Crowley family.
Dialogue and details are based on Dr. Daniel Birnbaum’s recollections in an interview on November 24, 2004, and also on John and Aileen Crowley’s recollections in interviews in 2004.
Dialogue and details in this section are based on recollections of John and Aileen in interviews in 2004.
Chapter 3
Dialogue and details are based on recollections of Dr. Birnbaum in an interview in 2004, and John and Aileen in interviews in 2004.
The incidence of Pompe disease is still not certain. Dr. Arnold Reuser, a professor at Erasmus University in Rotterdam who has researched the disease for decades, said in an interview on May 12, 2006, that the best estimates range from one in 40,000 people to one in 100,000 people worldwide affected with the disease.
Chapter 4
Information in this section on scientific history of development of a Po
mpe treatment is from The Metabolic and Molecular Basis of Inherited Disease, Eighth Edition, McGraw-Hill, New York, chapter by Hirschhorn R, and Reuser AJJ: Glycogen Storage Diseases Type II. The scientific history is also based on interviews with Dr. Y.T. Chen on April 15, 2004 and April 9, 2006; Dr. Rochelle Hirschhorn on May 10, 2006; and Dr. Arnold Reuser in 2004 and on May 12, 2006.
Hers HG: Alpha-glucosidase deficiency in generalized glycogen-storage disease (Pompe disease). Biochem J 86:11, 1963.
Dr. Hirschhorn interviewed May 10, 2006, and Dr. Reuser, interviewed in 2004 and again on May 12, 2006, confirmed this description of their race to clone the gene, which is backed up by their papers, listed below. Martiniuk F, Mehler M, Pellicer A, Tzall S, Gundula LB, Hobart C, Ellenbogen A, Hirschhorn R: Isolation of a cDNA for human acid alpha-glucosidase and detection of genetic heterogeneity for mRNA in three alpha-glucosidase deficient patients. Proceedings of the National Academy of the Sciences, 1986.
Hoefsloot L, Hoogeveen-Westerveld M, Kroos M, van Beeumen J, Reuser AJJ, Oostra BA: Primary structure and processing of lysosomal alpha-glucosidase. The EMBO Journal, 1988.
Martiniuk F, Mehler M, Tzall S, Meredith G, Hirschhorn R: Sequence of the cDNA and 5’-Flanking Region for Human Acid Alpha-Glucosidase. DNA and Cell Biology, 1990.
Jan van Heek, in an interview on May 26, 2004, recalled meeting with Chen and Reuser in the 1990s and not doing any deal because the project seemed too risky.
Duke University Medical Center press release from February 1998, provided by Duke University Medical Center Press Office.
Duke University Medical Center press release from February 1998.
Dialogue and details in this section are based on an interview with Dr. Alfred Slonim on March 15, 2004, and interviews with John and Aileen that year.
Dialogue and details of this meeting are based on interviews with Randall House on December 6 and 7, 2004; an interview with Slonim in 2004; and interviews with John and Aileen in 2004.
Chapter 5
In interviews on May 19, 2006, Brian Markison, John’s boss at Bristol-Myers, and Sandra Holleran, Aileen’s aunt, confirmed this account of how John got his first interview at the company.
Chapter 6
Information from interviews with Randall, Marylyn, and Tiffany House on December 6 and 7, 2004, and Marylyn and Tiffany again on May 22, 2006.
Dialogue is based on John’s recollection of the conversation; Randall in interviews in 2004 did not recall the conversation but says it may have occurred and escapes his memory today; he and Marylyn agreed in interviews that they were unhappy that John was starting his own foundation, believing it would be a distraction and take resources away from their own.
Dialogue and description in this scene are based on John’s recollections; I tried in vain to reach Gerben Moolhuizen by phone and e-mail at work at OctoPlus, a drug development firm in Leiden, Netherlands, in May 2006.
Information in this scene is based only on the recollection of John. I made several failed attempts to reach Moolhuizen by phone and e-mail at his job at the Dutch firm OctoPlus.
Rein Strijker declined to be interviewed for the book, saying this in an e-mail about John’s visit described in this scene: “I indeed clearly remember his visit to Geel during which he offered a large amount of money if his children could participate in an early clinical trial. At that time we took the position that money was not a good criterion for inclusion in such a trial. If I remember correctly, his children had a somewhat atypical form of Pompe disease and could not be included in the early study. He later became involved with Novazyme and Genzyme and was, in that context, closely involved with the situation that led to the (almost) going down of Pharming. As you may imagine, I do not have much respect for the way he has operated in this matter (even though I have sympathy with and feel sorry for the situation with his children). Hence, I do not wish to spend more time on contributing to a book that pays tribute to Mr. Crowley.”
Since I couldn’t speak to Strijker, I wasn’t able to try to reconcile his recollections with John’s.
Chapter 7
Markison and John, in interviews in 2006, provided these details of his job at Bristol-Myers.
Dialogue and details are based on interviews with Dr. Marc Hofley on April 7, 2004, and Marty and Kathy Holleran on March 5, 2004, as well as on interviews with John, Aileen, and Joe Crowley in 2004 and 2005.
Dialogue and details are based on interviews with Greg Assink in 2005 and Greg and Deborah Assink on April 9, 2006, and interviews with John in 2004.
Chapter 8
Dr. Nina Raben in an interview on March 29, 2005; Marylyn and Randall in interviews in 2004.
Dialogue and details are based on John’s recollections; Randall does not recall the details described here, but says the conversation may have occurred; he and Marylyn agree with the basic point, which is that they didn’t want John to start his own foundation, believing it would be a distraction and take resources from their group, and that they were doing everything possible to move research forward.
Dr. Paul Plotz, in an interview on March 29, 2005, said he believed anybody who wanted to attend an NIH-sponsored event should be allowed to do so, and he may have made the phone call to Randall or Marylyn, but he couldn’t specifically recall doing so. Marylyn, in an interview in 2006, said she recalled Dr. Plotz insisting John be allowed to attend.
Marylyn, in interviews in 2004 and 2006, agreed she didn’t want John to attend but relented and allowed him to do so, under pressure from Dr. Plotz. She confirmed John’s recollection of this phone call, and said she was mean and intimidating. She says she found him pushy, unprofessional, and interfering and worried he would disrupt the plans in place for her daughter to be treated in Pharming’s clinical trial, expected to begin soon. In retrospect, now that tempers have cooled, she said she understood why John pushed so hard to attend.
Dialogue and details that follow are based on John’s recollections in interviews in 2004.
Dialogue and descriptions in this scene based on John’s recollections; I tried in vain to reach Gerben Moolhuizen by phone and e-mail at work at OctoPlus, a drug development firm in Leiden, Netherlands, in May 2006.
Dialogue and details are based on recollections of Dr. Alfred Slonim and John in interviews in 2004.
Dialogue and details are based on the recollections of John in interviews in 2004 and Reuser in an interview in 2006.
Description of presentation is based on recollections of Dr. Y.T. Chen and John in interviews in 2004 and checked with Chen in another interview on April 9, 2006.
Description of presentation is based on recollection of Dr. Frank Martiniuk in an interview on January 17, 2006, and John in interviews in 2004.
Description of William Canfield’s presentation is based on interviews with him on May 5 and July 9, 2004, and recollections of Slonim and John in 2004.
John remembers meeting Canfield at this meeting, although Canfield, in the interviews in 2004, said he didn’t recall being introduced to John at that meeting. Slonim, in his interview in March 2004, said he remembered introducing them.
Dialogue and details are based on John’s recollection. Randall, in interviews in 2004, said he didn’t recall stopping John from getting on the bus, or saying the quotes attributed to him. He said he may have kept John off the bus and said these things and simply doesn’t remember. In retrospect, Randall said he understands why John was trying to get into the meeting and believes he was doing the right thing, but he found John’s efforts threatening at the time because Tiffany was so sick and plans for her to get treated in Pharming’s upcoming trial were so tenuous. Randall said he worried that John’s aggressive efforts to save his own kids would derail the plans to get Tiffany in the Pharming trial.
Chapter 9
Dialogue and details in this chapter are based on John and Aileen’s recollections of what happened and what they said at the time.
Dialogue and details are based on recollections of Ed and Joh
n in interviews in 2004 and 2005.
Chapter 10
Dialogue and details are based on recollections of Sharon Dozier, John, and Aileen in interviews in 2004.
Chapter 11
Slonim, in an interview in 2004, recalled describing Martiniuk this way to John; John, in interviews in 2004, remembers Slonim describing Martiniuk this way.
Dialogue and details in this scene are based on recollections of Martiniuk in an interview in 2006, and John in interviews in 2004.
Dialogue and details in this scene are based on an interview with Martiniuk in 2006 and interviews with John, Aileen, and John’s mother Barbara in 2004.
Dialogue and details in this scene are based on recollection of Chen in interviews in 2004, and John in interviews in 2004.
Dialogue and details are based on John’s recollection in interviews in 2004 and recollections of Deb and Barry Koncel in an interview on November 27, 2004.