A Life Everlasting

by Sarah Gray

  That was just the first phase. In the second phase, NDRI worked with five OPOs—Gift of Life Donor Program of Philadelphia, LifeNet Health of Virginia Beach, Center for Organ Recovery and Education in Pittsburgh, Washington Regional Transplant Community in Washington, and LifeGift in Houston—for an additional 150 organ donors and 100 tissue donors.

  The specimens were all sent to the National Cancer Institute’s Human Biobank, except for the brains and spinals cords. Those latter donations went to Dr. Mash’s Brain Endowment Bank at the University of Miami, where scientists isolated cells from various regions of the brain and sent them to the GTEx lab, storing the remaining tissue for future studies of the central nervous system.

  The excitement in the scientific community over this project is palpable. Meenhard Herlyn, D.V.M., D.Sc., a professor at Wistor Institute in Philadelphia and chairman of the board at NDRI, said, “GTEx has an ambitious program to finely analyze genetic and epigenetic variations in human cells within each of the different organs. The results, once we learn to interpret the massive amounts of data, will bring us one step closer to understanding the many subject signatures of human organs.”

  It was also notable that, given the priority assigned to transplant versus research by organ-procurement organizations and eye and tissue banks, Richard D. Hasz, the vice president of clinical services at the OPO Gift of Life, had this to say: “Research is a fundamental part of our mission, and organ transplantation, as it exists now, would not exist without effort like this. GTEx provides an additional opportunity to create a legacy for donors and their families, with the ultimate goal of contributing through research for the betterment of mankind.”

  The third and final discussion of the day focused on improving the matching function of donating for research. The featured panelists were Barbara Koenig, a professor of medical anthropology and bioethics at the University of California, San Francisco; Helen Moore, chief of the Biorepositories and Biospecimens Research Branch at the National Cancer Institute; Kevin Myer, president and CEO of the OPO LifeGift in Houston; Timothy Westfall, director of Biopta, Ltd.; Dr. Serge Przedborski, a renowned professor of neurology and vice-chair of research in the departments of neurology, pathology, and cell biology at Columbia University; and Susan Stuart, president and CEO of the Center for Organ Recovery & Education in Pittsburgh.

  Medical science had made enormous and unforeseen strides in the years since NDRI started its work collecting pancreases for investigators to study diabetes. Until now, the focus has been on collecting as many organs and tissues that are unsuitable for transplant as possible. But as researchers’ investigations, and therefore their needs, become more sophisticated, NDRI has worked to develop new tactics for identifying donors who match the new and unique requests.

  Traditionally, the role of OPOs has been to recover organs for transplant, not necessarily organs for research. In the United States alone, more than 123,000 people are waiting for a life-saving organ to be available. In the last few years—and especially with the arrival of these enormous government-sponsored research endeavors—the number of requests for research tissue has increased exponentially. The Center for Medicare Services (CMS) became the overseer of the entire network of organ-procurement organizations across the country, and all the different kinds of organ and tissue recoveries they now perform—all because of kidneys.

  Back in 1972, the Social Security Act created an entitlement covering the cost of dialysis and transplant for all patients suffering from end-stage renal disease (ESRD) who were eligible for Medicare coverage, which covers approximately 90 percent of all patients with this condition. Today, OPOs are largely reimbursed by hospitals when they provide organs for transplant, but if there is any shortfall, Medicare makes up a small portion of the difference—but only in the case of kidneys. In order to be eligible for that reimbursement, all OPOs must meet the performance standards required by CMS for OPO certification.

  In 2006, CMS added a third metric for certification—donation for research. The “Medicare and Medicaid Programs Conditions for Coverage for Organ Procurement Organizations (OPOs) Final Rule,” published in the Federal Register on May 31, 2006, reads: “Like organs for transplantation, organs for research are a precious national resource. We believe OPOs should recover organs for research whenever possible to aid researchers looking for new therapies for debilitating and fatal diseases, many of them the same diseases that cause end-stage organ failure in patients waiting for transplants. Although recovering organs for research is not an OPO’s primary mission, the organs it places with researchers may help lead to treatments or cures that will reduce the transplant waiting list as surely as organs that are used for transplantation. We believe that providing an incentive for OPOs to recover organs for research will increase the number of organs available to researchers throughout the country. . . . Nevertheless, while recovering organs for research is vitally important, we do not want OPOs to recover organs for research at the expense of organs for transplantation.”

  According to Lori Brigham, president and CEO of WRTC, who has been with the Washington, DC–based OPO since its inception in 1987, “It’s an enormous amount of work to do research recovery. You have to have the additional staff and surgical resources to be able to do that. WRTC oftentimes supports research recovery, and we do not get reimbursed fully for it. That’s one of the reasons a lot of OPOs are unable to strongly commit to the recovery of organs for research. The researchers will contact the OPO asking for various types of organs and tissues to be used in their research. But a lot of times they do not have the funding to pay for the recovery of the tissues and organs—the additional operating-room time; the addition of surgical staff to go into that operating room to recover that organ or tissue for that researcher; the preservation, packaging, and transportation of that tissue or organ sample. You also need to consider the additional time it takes to discuss the research with the family during the donation authorization process. There’s a considerable amount of work that’s involved in research donation and research recovery.”

  Immanuel Rasool, manager of research and living donation at WRTC, works closely with NDRI and other research organizations across the country. Rasool’s job is to find placements for organs and tissues with researchers; he also teams up with the International Institute for the Advancement of Medicine, the group that linked Bethany Conkel’s son, Amalya, up with researcher Scotty Bolleter. Rasool also reaches out directly to researchers at academic institutions in the Washington, DC, area.

  Rasool explained the growing challenge in research donation: “Researchers are picky about what they want. For example, someone may want only male skin, or skin from someone of a certain age.” He also pointed out a surprising bureaucratic obstacle that sometimes comes up: office hours. “Researchers need [to receive] the organ or tissue pretty quickly, but they may not be available twenty-four/seven. We could have a donor who is perfect match on a Friday night, and we can’t find researchers because they’re generally not working weekends.”

  Rasool concurred with recent research showing that the majority of potential donors would happily donate for research if they were given the option and the research was explained well to them or their families.

  The boom in stem-cell research has, for instance, created a demand for testes, which contain adult male germ line stem cells that can be altered into “embryonic-like” stem cells, according to scientists at Georgetown University, where one such study was being conducted. When Rasool first heard a request for this, he thought, How am I supposed to request testes from a grieving family? But when the reason was explained to families, many were happy to donate.

  Some tissues may not be needed immediately, so they are stored for the future—which is another part of what the GTEx project is about. Harvard University’s T. H. Chan School of Public Health has a huge stash of hair samples and freezers full of toenails—clippings from more than one hundred thousand people, if you can imagine such a thing—with which r
esearchers hope to better understand ovarian cancer. The idea is that blood will tell scientists what’s in your system only at the moment it’s drawn, but hair and nails hold onto trace elements and hormones, so scientists can check levels of these things over several months.

  Jeff Thomas of NDRI said that to him the big revelation about the GTEx project was that 70 percent of families agreed to donate when they were told about its aims. Thomas’s father, who was suffering from a form of frontal-lobe dementia, was signed up to donate to the University of Pennsylvania Perelman School of Medicine’s Center for Neurodegenerative Disease Research. Researchers are monitoring his disease progression while he’s alive, and then they will have his brain to study when he dies.

  “I’d like to think we’d get to the point where the general public was aware that research donation is an option and they can understand the benefits of that gift to future generations,” Thomas said.

  I was invited to speak at NDRI’s thirty-fifth-anniversary dinner that evening, which was being held in the imposing Lincoln Hall at the Union League of Philadelphia—a room dominated by portraits of past heads of the Union League.

  As Ross and Callum and I walked in, one of the first people we saw was Michael Vitez, who’d written about us in the Philadelphia Inquirer and who, fittingly, would be the emcee of the evening’s festivities. I chatted with him about how popular his story had been—another sign that Thomas’s donation had reached and affected so many lives.

  As the speeches began, I realized that I was part of a much bigger effort to move science forward. Bill Leinweber, the president and CEO of NDRI, welcomed us all and laid out all the things NDRI does, and then Michael Vitez called me up to the podium. I was joined onstage by Ross and Callum, now five and a half years old and getting used to Mommy talking about his brother, Thomas, in front of people.

  As I stood in front of hundreds of faces, I realized that these professionals understood, more than any other people on the planet, this major event in our lives. These were my people now.

  In my speech I explained that I had initially been curious about where Thomas’s donations went and what difference they made, and that although I might have been the first person to go on this quest, I didn’t want to be the last. I praised NDRI: given all the privacy issues, they could have stopped me, but they only helped. And I closed with a message about the power of sharing information and included the story of Matt Might, which Seth Mnookin told in the New Yorker in July 2014. Matt’s child was diagnosed with a genetic defect so rare that no research study would invest the money to study the disorder unless other patients were found. Matt then wrote a long essay on his own website called “Hunting Down My Son’s Killer.” The piece went viral on Twitter and Reddit and was republished in the tech blog Gizmodo; as a result, he was connected with thirty-six more patients with the same disorder. He essentially crowdsourced a rare-disease research sample—a critical step in securing research. The NIH began a formal investigation of the disease, and in less than four years that research was already translating into drugs to treat it.

  While I was talking, Callum stood quietly with his dad. My boy seemed so at ease in the spotlight now—I guess he’d had some practice—and everyone was impressed by how calm and good he was, this boy who had cried out when his twin took his final breath five years earlier.

  Back at the table, everyone praised Callum.

  “Mommy, am I famous?” Callum whispered to me.

  “Yes, a little bit,” I said.

  Later, NDRI recognized various OPO donation partners from around the country who had worked on the GTEx initiative, and I realized again how the effort to support research is fueled by hard-working people from all over America. There was the Center for Organ Recovery & Education (CORE), based in Pittsburgh and servicing 155 hospitals mostly in western Pennsylvania and West Virginia; the Gift for Life Donor Program, which works all the way from Delaware to New Jersey; Texas-based LifeGift; LifeNet Health from Virginia Beach, which covers southern Virginia; and my beloved Washington Regional Transplant Community.

  NDRI then introduced the inaugural D.Walter Cohen Service to Science Award, and gave it to D. Walter Cohen himself. A periodontist by trade, Dr. Cohen led NDRI until he became its chairman emeritus at the start of 2007.

  Dr. Cohen took the stage and took us all back to the moment in 1952 when his life changed. He had been attending a lunch at Princeton University that was also attended by Albert Einstein. The meal had been a benefit for the Hebrew University, and one of the financial donors offered to double a $250,000 pledge if Einstein would shake the hand of the donor’s wife. Hearing this, Einstein jumped out his chair so fast to grab her hand that his spectacles skittered across the floor. Dr. Cohen said that such an image of putting ego aside to help a good cause had stayed with him to this very night.

  As the attendees put on their coats, said their good-byes, and headed out into the chilly October night, I thought of the past and the future. Albert Einstein, born in 1879; D. Walter Cohen, born in 1927; and Thomas Ethan Gray, born in 2010—all three forever connected through this evening, this organization, and this effort.

  MARA’S STORY

  A Sword and a Shield

  Mara Cray was born in 1996 in Voorhees, New Jersey, and was diagnosed with cystic fibrosis at birth. Her parents, Sharon and Mike, were already familiar with the disease because her brother Ian, five years old, also had it. (Her other brother, David, is eight years older but doesn’t have the disease. Growing up with two sick siblings led him into the medical field, but he opted to treat animals rather than people.)

  Growing up, Mara and Ian went to doctor’s appointments together. “I was the youngest, so I would do whatever my older brother did anyway. Just the fact that my older brother had CF meant it was okay for me to have it, too,” said Mara.

  Since CF was somewhat normal in the Cray household, Mara didn’t think much about it. She wasn’t uncomfortable telling people she was sick, taking her medication in the school cafeteria, or sucking on an inhaler in gym class. And because she didn’t have a problem with it, her friends didn’t, either, visiting her in the hospital when she needed IV antibiotics for a few weeks every year, but not making a big deal about it. CF was just part of her life.

  Yet she had some unique challenges that her non-CF friends didn’t have. CF lungs are like fly traps for bacteria. A person without CF can easily cough out invaders, but a CF patient cannot. Because of this, CF lungs provide a warm, humid, permanent home where bacteria can get comfortable, learn to resist antibiotics, and develop into “superbugs” such as Pseudomonas aeruginosa, the most common cause of mortality among CF patients. These superbugs are harmless to someone with healthy lungs, who can simply cough them out, but they can be deadly for CF patients. A superbug called Burkholderia cepacia is so dangerous that the Cystic Fibrosis Foundation has banned anyone with a positive B. cepacia culture from any foundation events, meetings, or offices.

  Some of these superbugs were already detected in Mara’s lungs when she was five years old. Because she took antibiotics so frequently, the bacteria learned to adapt over the years. This meant that great care had to be taken when Mara visited places that could harbor bacteria—places like airplanes, public bathrooms, and gym locker rooms. In addition, environmental irritants such as bathroom cleaners and smoke can be a hazard for CF patients, who already have compromised lung capacity. As a result, Mara suffered through more than one campfire with her friends, never able to find a seat in the circle where the smoke didn’t find her.

  “Campfires I hate,” Mara says. “The idea is nice—sitting around a fire with your friends and all that—but five minutes in, I have no voice and I’m coughing uncontrollably.”

  Although Mara attended a mainstream school for most of her childhood, many exceptions had to be made to allow her to do this. She and her parents met with teachers and administrators to adjust her schedule and workload. Mara needed at least one hour of treatment per day, consisting of two
to four medications inhaled by nebulizer, plus airway clearances, which are effected either with a compression vest or chest physical therapy (clapping) every morning. As a result, the family arranged Mara’s classes so that she could arrive later than the other kids. In the evenings, the same regime had to be followed. If she was too sick to complete homework assignments, arrangements were made for her to do make-up work, and, not surprisingly, she was not strictly held to the school’s attendance policy.

  Having a condition like CF can be emotionally isolating for patients. Whereas many people with chronic illnesses are able to connect with peers in disease-specific support groups, meeting others with CF can be life-threatening. Because of the possibility of cross-infection, CF patients need to maintain a distance of at least six feet from one another, since that’s the distance droplets from sneezes and coughs can travel. Mara likened it to CF patients having a group restraining order against themselves. Fortunately, modern-day sufferers at least have the Internet, where they can join online support groups, but it’s still not quite the same as seeing people face to face.

  When Mara was fifteen years old she began experiencing a significant decline in her energy levels and respiratory health. Her doctors would sometimes prescribe oral ciprofloxacin (Cipro) to treat infections, but when it was bad they recommended IV antibiotic treatments of tobramycin, together with a second antibiotic to target whatever bacteria she was hosting at the time. The drugs knocked out her lung infection but gave her side effects of terrible nausea, fatigue, and depression. One other side effect that CF patients are warned about: the medications inflame and weaken tendons and joints. Mara depended on a regular mile-long run to help clear her airways, but when she was enduring a round of antibiotics, she couldn’t run, which made her breathing worse.