Chapter 15

Cystic Fibrosis, the Most Heartbreaking Lung Disease

No one understands the importance of the breath better than Sarah Murnaghan and her family. Born in 2003, Sarah appeared to be healthy at birth, and even though she was born premature, at thirty-six weeks, Sarah was an average size and weight. At home though, her mother, Janet, soon realized there was something very wrong, as Sarah wouldn’t eat, wouldn’t stop crying, and was unable to gain weight normally. Even after she drank milk, her diaper was almost never wet. The pediatrician told Janet that everything was okay, but even as a new mom, Janet knew something wasn’t right. And she was correct. After eighteen agonizing months of prodding physicians, Sarah proved to have cystic fibrosis.

Janet and her husband, Fran, were in shock. Things that happened to other people had happened to them. The survival statistics for CF weren’t encouraging, but neither were they completely devastating. The average lifespan for children with the disease at that time was twenty-eight years, and it had gone up ten years in a generation.

Even with effective medicines, CF requires a tremendous amount of work, most of it directed at the lungs, the organ responsible for 90 percent of the mortality associated with the disease. Cystic fibrosis patients make too much mucus, which gets stuck deep in the lungs, providing a fertile breeding ground for bacteria. Infections and lung destruction follow in a mutually reinforcing cycle of dysfunction.

To help prevent or, more realistically, delay damage to the lung tissue, patients inhale multiple medications every day to break up the mucus. After taking the medicines, they must expectorate the secretions, either with vigorous coughing or with chest physical therapy, in which a parent pounds on the child’s back to agitate the mucus and move it out of the airways. The work is intense and usually requires an hour in the morning and another hour at night, even with the advent of protein modulators. And like Sisyphus’s task of rolling the stone up the hill, it must be done every day.

Janet and Fran did Sarah’s airway clearance religiously, gave her the inhaled antibiotics, and brought her to her doctor at the Children’s Hospital of Philadelphia every three months. Most CF patients don’t manifest debilitating symptoms until they are in their twenties or, if they’re lucky, their thirties. But the late diagnosis at eighteen months had cost Sarah, and one of her lungs was already permanently damaged. By the time Sarah was seven, she was going into the hospital every few months for intravenous antibiotics. Her lung function would stabilize, and she and her parents would breathe a sigh of relief. But then another infection would develop, along with diabetes, osteoporosis, asthma, and malnutrition. Sarah missed a lot of the second grade, and with the threat of viruses and bacteria at school, she began homeschooling. She never complained and never felt sorry for herself, but it broke her parents’ hearts that she couldn’t lead a normal life.

Then, when she was nine, Sarah ended up in the hospital and could not return home. Her lung function was at 30 percent, and the bacteria that colonize every CF patient had become completely resistant to antibiotics. She needed to be put on oxygen, and she struggled to walk. Weight loss became an issue, and she dwindled to fifty pounds. Her parents saw the happy daughter they once knew start to slip away, replaced by a girl robbed of her childhood.

With this level of illness, Sarah couldn’t go on much longer. The time to change course in the management of her disease had come, and Dr. Howard Panitch had to break the news to the family. The Murnaghans trusted Dr. Panitch unequivocally. He had been a cystic fibrosis doctor for thirty years, and Sarah’s physician since her diagnosis. His refusal to accept average outcomes matched Janet’s approach perfectly from day one. Even so, when he told Janet and Fran that Sarah would need a lung transplant to survive, they were stunned. Nonetheless, they both accepted his assessment and were soon introduced to Dr. Samuel Goldfarb, the medical lung transplant doctor.285

What Dr. Goldfarb told the Murnaghans next stunned them even more: while Sarah needed a lung transplant, it was doubtful she would live long enough to get one because she was subject to what was known in the lung transplant world as the “under-twelve rule.” Adults are listed for lung transplants in an order based on their level of illness. But because of a lack of data on how pediatric patients should be prioritized, children under the age of twelve were, in 2012, left in an antiquated system in which patients simply got in line. Those who were able to stay alive long enough would get their new lungs; however, because of the paucity of pediatric lung donors, many children died while on the waiting list. A little girl as sick as Sarah would almost certainly be one of those to die. There was almost no chance she would last long enough to get a new set of lungs.

Janet Murnaghan was incredulous when she learned how lung allocation was organized. To her, patients at the greatest risk of dying should get organs first. The system for adults had shifted away from the first-come-first-served method in 2005. Assigning organs based on need was an ethical, equitable principle that nobody would contest. But the under-twelve rule was still in place, and it would not be easily changed.

With Sarah stuck on a long waiting list serviced by a scarcity of donors and unable to get into the more sensible adult system, Janet made a simple but powerful statement: “The only thing standing between my daughter living and my daughter dying is the fact that she’s ten and not twelve. That’s unreal to me.”286

Janet’s statement, and her subsequent fight on social media, in the press, and ultimately in the courtroom, brought to public attention the rationing of organs, patients dying on waiting lists, and, most important, the fate of a little girl with a lethal genetic illness and scarred lungs. Many people would weigh in, including the head of the US Department of Health and Human Services, federal judges, doctors, ethicists, the entire lung transplant community, and people throughout America and the world. In the end, the outcome left some people satisfied, and others completely dissatisfied. One thing did remain steadily clear throughout the whole ordeal: a little girl, her mother, and her family, refused to give up in their quest to restore the breath of life to one from whom it had so unfairly been taken away.

I attended my first transplant lecture during year one of my lung medicine fellowship. The speaker’s first slide was simple: a glass of water exactly half full. Over the course of the next hour, he explained the meaning of the image as it related to lung transplants. The glass half full gave patients a new lease on life—a new set of lungs and a vastly improved breathing experience. The glass half empty was the stark reality that lung transplants are fraught with potential life-threatening problems, such as infection and rejection.

Each lung transplant candidate must weigh the benefits and drawbacks of a transplant. For Dr. Panitch, Sarah, and her parents, the conversation was straightforward. Sarah was stuck in the hospital on potent antibiotics with an oxygen mask strapped to her face. Pain was a big issue from compression fractures in her back due to long-term steroid use. At night she played monopoly with her mother, and before bed they would turn up the air conditioning to simulate the breeze of a beach, the air rocking the paper lanterns on the ceiling. Her friends went to school every day, while she went about the business of trying to keep herself alive. Sarah and her family were forced to see lung transplant as a glass half full, and to take their chances with infection and rejection.

Once the transplant decision had been made, Janet’s crusade to change the rules began. The issue with lung transplants—and with all transplanted organs, she discovered—is the simple fact that there are more people in need of an organ than there are healthy organs available. This creates a system in which patients die on waiting lists. For the years between 2015 and 2019, 935 patients died on the lung waiting list, an average of 187 patients per year, or one every 47 hours. The statistics for other organs are similar. In 2019 alone, 5,445 people died on waiting lists for all types of organ transplants. From 1995 through 2019, 166,223 patients died awaiting a transplant.287

When resources are limited, a basic ethical tenet is that those who need the resource the most, namely those who are the sickest, should be prioritized. The system for prioritizing adult lung transplants changed in 2005 because of an order from the Department of Health and Human Services, known as the “final rule,” which states that lung transplant allocation must take a patient’s level of illness into account when prioritizing their position on the waiting list. But level of illness was not the only criterion. If only the sickest patients received transplants, many of them would never recover, and the organs would essentially go to waste. A measure of a patient’s ability to survive after a transplant had to be added into the calculation.

Balancing level of illness against the ability to bounce back from a big surgery is difficult in lung transplants. Given the overall poor outcomes and ubiquity of complications, transplanting lungs is a high-wire act compared to transplanting other organs. Assessing a patient’s likelihood of dying soon from their lung disease versus their ability to live after a transplant was considered impossible. Thus, the original system of getting in line and waiting for new lungs remained until 2005, long after it had been abandoned in liver and kidney transplants.

Using data from previous lung transplants, physicians and statisticians developed a new system called the Lung Allocation Score (LAS). Each patient awaiting lungs received a score between 0 and 100, with those scoring closer to 100 being highest priority on the waiting list. The equation to calculate the score was based on how likely the patient was to die while on the waiting list matched with how likely the patient was to be alive one year after the transplant. These two calculations helped balance justice—the principle that everybody should have equal access to resources—with utility—the reality that a limited resource needs to be allocated to those who will benefit the most from it.

The system still wasn’t perfect, as the calculations were little more than educated guesses, and unlike the system used to allocate liver transplants, the equations used for lung transplants were not prospectively validated. Prospective validation is a big deal in medicine. The best way to derive the calculations for balancing need of a transplant with likelihood to survive a transplant would be to create two groups of patients, one that received transplants and one that did not, and then compare how long they lived. This obviously could not be undertaken ethically, since patients waiting for a lung transplant could not be denied an organ just so formulas could be derived. In contrast, liver and kidney formulas can be more accurate because their absolute numbers are so much larger that statisticians have more data to work with.

Fortunately, the Lung Allocation Score system worked, despite its potential flaws. The number of deaths on the waiting list plummeted in the years after the new system was implemented, from an average of more than four hundred to two hundred per year. Almost as important, there was no big change in one-year mortality, or even five-year mortality. The doctors were performing transplants on the sicker patients, saving lives on the waiting list, and not putting organs to waste.288

However, the issue of children under twelve remained a problem well beyond 2005. Originally, doctors believed that size disparity would prevent an adult set of lungs being successfully transplanted into a child. Also, an LAS number for children under twelve could not be easily formulated since there was so little data for statisticians to draw on: between 1990 and 2001, seven thousand adult lung transplants had taken place in the United States, yet only four hundred transplants had been performed on pediatric patients in the same time period. Pediatric lung transplants were also done to cure different diseases than adult lung transplants, conditions like congenital protein deficiencies and heart diseases that also affect the lungs. Different diseases do not behave the same way under transplant conditions. The LAS formulas could not be easily tweaked to fit the younger population because of this disparity.

Given the small number of under-twelve transplants, statisticians felt they did not have enough data to devise equations to answer the two dispositive questions: Who is going to die awaiting a transplant, and who is going to benefit the most postoperatively? So for eight years after 2005, the dual allocation system, however flawed, remained in place. Those twelve and over could be eligible for adult lungs, while those under 12 remained in their own donor pool, ranked by level of respiratory failure, blood type, and time spent on the waiting list—until Janet Murnaghan started questioning the system’s ethics.

The first thing Janet recognized was that the under-twelve rule was a completely arbitrary designation. If organ or body size was an issue, then age was not really important: some ten-year-olds were as big as thirteen-year-olds, or even eighteen-year-olds. The reverse was also common. Janet also found out that size was not necessarily an issue at all. Each human lung has three lobes on the right and two on the left. These lobes can be separated and trimmed out as needed. Several published reports concluded that an adult set of lungs could be cut to fit a child, with good outcomes.

A final source of frustration for Janet was that Sarah had a disease for which an LAS predictive model existed. A claim could not be made that her disease was unique to pediatrics. Cystic fibrosis was a common reason for adult transplant, so basic expectations existed of what to anticipate at certain levels of illness. There was no evidence that the predictive models for dying on the waiting list or being alive one year after transplant would be any different for kids with CF than for adults.

Janet and her family felt they could deliver more than enough proof that the under-twelve rule did not fulfill the transplant principle of justice. Janet also felt that if doubt remained as to what the policy should be, it should be rewritten to err on the side of being inclusive rather than exclusive. The rule change would affect few patients, but at the same time benefit very sick children. But not everybody agreed. Some people, in fact, vehemently disagreed with Janet, including some of the leading transplant experts in the world. They argued that the systems had been designed with the best available evidence at the time, and rules shouldn’t be changed based on single cases for those with the loudest voice or deepest pockets.289

With their daughter slipping away, Janet and Fran saw two options. Sarah had been listed for a transplant for over a year, and none had materialized. Now was the time to either let nature take its course or investigate the possibility of trying to get on the adult list for lungs. They asked Sarah if she wanted it all to stop. Fully aware of her situation, Sarah was unequivocal: “I will never give up, ever, so don’t you give up on me!”290

With a clear answer, Janet asked the transplant surgeon and medical doctor whether they would be willing to do a lobar transplant on Sarah, that is, to cut the lungs from an adult donor into lobes, extract the two best, and make them fit into Sarah. Their answer was unambiguous: not only would they be willing to do it, but based on published reports, they thought the transplant would be successful. With newer immunosuppressant drugs and care, and increased understanding of rejection issues, lung transplant patients were living longer than ever before. Even more important for Sarah, within the group of transplant patients, CF patients excelled. The fifty percent survival rate for all patients had risen to somewhere between six and seven years. For CF patients as a subgroup, it was about seven and a half years in 2013.

Now Sarah and her team just needed to get that blessed organ, and the medical community needed to figure out if it was ethical to give Sarah one.

In 2013, Sarah Murnaghan hoped to receive new lungs, exactly thirty years after Joel Cooper had accomplished the first successful transplant. A former public relations executive, her mother determined to put pressure on the United Network for Organ Sharing (UNOS), the nonprofit group that manages the nuts and bolts of every organ transplant in the country through the Organ Procurement Transplantation Network (OPTN). With advice from the transplant doctors, surgeons, ethicists, and epidemiologists, UNOS and the OPTN make all the rules for how organs are distributed in the United States.

Janet crafted a letter to her friends, telling them of Sarah’s dire condition, and how the only way to save her was for her to get on the adult list in the appropriate place as dictated by her level of illness. She hit “send” on the e-mail at 10:00 p.m. on Friday, May 24, 2013, then closed her computer and got into bed with Sarah, among the tubes and wires and beeping monitors, Fran asleep in the cot next to the bed.

The next morning Janet logged onto her computer, hopeful for a few replies—instead she had hundreds of messages, and a behind-the-scenes plan for a public relations blitz had developed overnight. The Philadelphia Inquirer ran the first story, and then the family was contacted by CNN. A crew happened to be in town over the Memorial Day weekend, and was sent to Sarah’s hospital. The piece aired on CNN on May 27, starting with a video of Sarah, sitting on the edge of her hospital bed with an oxygen mask strapped to her face, singing “Twinkle, Twinkle, Little Star” while striking the notes on a xylophone.291 Entire elementary schools and nursing homes around the country wrote letters of support.

The OPTN, however, did not budge, and their physician representative replied: “It tugs at my heart. It’s not a perfect system. There is no perfect system. It’s the best we can do right now. If I change the system to give Sarah an advantage, there’s another patient, very likely an adolescent, who then gets a disadvantage. We’ve built a system that tries to be as fair to everyone as possible.”292

In response, Janet and Team Sarah started a petition at change.org, firmly believing there was no medical reason why Sarah or any other youth under twelve and in the same circumstance shouldn’t be allowed to get in line for an adult organ. Five hundred people signed it. Then one thousand. Then one hundred thousand. Then four hundred thousand. Each signature generated an e-mail to the president of the OPTN. His inbox crashed after forty-eight thousand.

Another turning point was reached when senator Pat Toomey and then-congressman Pat Meehan, of Pennsylvania, joined the cause and reached out to Kathleen Sebelius, secretary of Health and Human Services. Janet and Sebelius talked on the phone, but Sebelius would agree only to review the policy, which would take months and be too late to help Sarah.

The arguments that Sebelius used to come to her decision had obvious merit. The lung transplant rules were set up in a transparent manner with the best evidence available at the time. If the injustices to the pediatric population were rectified, then injustices would potentially be done to another group. With a scarcity of organs, an adult set of lungs given to a pediatric patient could mean one more death on the adult waiting list. And even though ten case reports existed of pediatric patients doing well with adult lungs, thousands of cases supported the knowledge that adults do well with adult lungs.

Heartbroken over Sebelius’s stance, the family as a last resort took their case to the courts. The hearing was held on June 5, 2013, and was overseen by the federal judge for the Eastern District of Pennsylvania, Michael Baylson. The star witness was Dr. Samuel Goldfarb from the Children’s Hospital of Philadelphia, their lung transplant doctor. Judge Baylson got right to the point in his questioning: Would Sarah live as long as an adult after the transplant? Would her quality of life be good? Would adult lungs work on Sarah? Dr. Goldfarb answered each question in the affirmative. He explained to the judge that the under-twelve cutoff was arbitrary and not rooted in any science; it could easily have been a different number.

In a stunning rebuke to the OPTN and Kathleen Sebelius, Judge Baylson ordered a temporary suspension of the under-twelve rule, stating that it “discriminates against children and serves no purpose, is arbitrary, capricious and an abuse of discretion.”293 The Murnaghans were euphoric. Sarah’s transplant doctors could now calculate an LAS score that actually meant something. Given her level of illness, Sarah’s score put her at the top of the list for adult lungs.

An adult donor became available a week later. It was just in time, as Sarah had been sedated and placed on a mechanical ventilator a few days earlier, her lungs finally giving out under the weight of relentless infections, mucus, and fevers. The surgeons at Children’s Hospital of Philadelphia trimmed down the adult lungs, took Sarah’s old lungs out, put the two halves into her chest, sewed up her vessels, and released the blood and air into the donor lungs. The surgery had started at noon and had extended into the early evening. Everything went according to plan.

But when Sarah was wheeled out of the operating room, things started to go wrong almost immediately. The doctors couldn’t remove her breathing tube because the level of oxygen in her blood was much lower than expected. A chest X-ray was done, and it confirmed what everybody had dreaded: the lungs were failing, in spectacular fashion, and given the amount of inflammation seen on the chest X-ray, and the level of oxygen in her blood, it was clear that nothing could turn them around. The only option was to try for another transplant. In the meantime, the ventilator wouldn’t be enough to keep Sarah alive. The doctors were forced to put Sarah’s heart and lungs on a bypass machine, and keep her completely paralyzed, a very short-term stopgap prior to a second transplant. This was also the last try; precedent existed for one retransplantation, but not for a second.

Dr. Goldfarb and the transplant physicians calculated another LAS for Sarah to get her back on the list for a retransplant, the number being extremely high again because of her catastrophic level of illness. Three days later, the doctors got a call from the OPTN: a set of lungs had become available, but they contained a clear area of pneumonia. They could try to wait for better lungs, or they could cut away the pneumonia and treat the remainder of the lungs with high-powered antibiotics. In consultation with the Murnaghans, they choose to take the lungs with pneumonia.

For the second time in a week, a greatly diminished Sarah went back into surgery. The surgeons cut out the infected portion of the donor lungs and began the surgery again. Afterward, they didn’t try to remove the oxygen tube right away, or even close up Sarah’s chest; her lungs expanded and contracted in full view underneath a thin, transparent protective film, her heart beating in the middle.

Sarah stayed on the ventilator for the next week while the team balanced the inherent opposites of fighting an infection with antibiotics and warding off rejection with immunosuppression. The swelling in her body slowly improved, and they began weaning her off of the ventilator. A week later, they took Sarah back to the OR and closed her chest. A day after that, they woke her up for the first time, and she somehow summoned the energy to sit on the edge of the bed. The next day, she sat in a chair, and the day after that she painted a picture while sitting in that chair. She was home at the end of August—on a ventilator, but home nonetheless.

Sarah stayed in the media for a while after her second transplant, but like many stories that have captured the front page, hers faded out, and she was left alone to do the work of rehabilitation. I followed her story for a while but then, like most, lost track of it. Sarah left the headlines, and discussions before conferences and after rounds in the hospital strayed to other topics.

In February 2014, about nine months after Sarah’s transplants, I attended a dinner to honor unsung heroes in cystic fibrosis. Every year, each cystic fibrosis center in the Philadelphia area nominates a member of a care team as well as a patient. I was the physician representative from my center. The dinner landed on Valentine’s Day that year, and more than five hundred people were in attendance. During the dinner, Dr. Howard Panitch stepped to the microphone to give out the Shining Star Award to the person with cystic fibrosis who had displayed the most courage and overcome the most adversity in the previous year. That year the award was going to Sarah Murnaghan.

“As a physician in an academic medical center, I am used to my role as a teacher, both to other medical professionals and to families,” Dr. Panitch said. “Occasionally, though, we are taught special lessons from our patients that profoundly influence how we care for others, or how we aspire to conduct ourselves. I am humbled to be one of Sarah’s students, and hope that I can meet my own challenges with the same grace and determination that she demonstrates every day. The Shining Star Award recognizes a person with CF who strives to live life to the fullest and who overcomes the many obstacles that CF presents. I can think of no one more deserving of this award than Sarah Murnaghan. Please join me in congratulating her on receiving this year’s Shining Star Award.”294

In a purple sparkle dress and black shoes, Sarah stood up out of her wheelchair and approached the microphone. Her voice was a whisper, but her quiet, simple words resonated. We all stood transfixed by her.

“Special thanks to my doctor, and there are a few other things I’d like to share. I have a really strong family, the best in the world, my mom and dad never left my side, my brother and sister and cousins cheered me on. Aunts, uncles, and grandparents, you name it, there is no give-up with this bunch. It is because of them that I knew that I wanted to live. And the one thing that I needed to fight is the most powerful weapon: God gave me bravery. The reason I survived two transplants, wasn’t just me, it was the bravery in me. And knowing that my family would never give up on me. And I know all CF kids and kids with other diseases, too, have that bravery in them. So my advice, whatever you are dealing with, young or old, is to be yourself. Look deep inside yourself for that bravery, and the reason to fight. For me it was my family. It may not seem to be there at first, but I promise you it’s there, and it will take you to the impossible if you just believe in yourself. Thank you.”295

The audience was quiet for a moment, and then it burst into applause. Some of Sarah’s friends from school had come with her, and they now swarmed her. A feeling of electricity was in the air. The politics, the ethics, all melted away for this moment as we all pondered the lessons Sarah had just imparted to us, and the fact that this girl, who had been through so much, was, at the age of eleven, teaching us about the meaning of life.

Joel Cooper once heard in synagogue, in reference to the parting of the Red Sea by Moses, that a miracle is an event that leaves you with an abiding sense of astonishment. That is the exact feeling I had that night after witnessing Sarah’s speech.

In June 2014, on the one-year anniversary of Sarah’s transplant, the lung transplant committee finally made official the rule that allowed Sarah to obtain an adult set of lungs. Other children are now free to apply for a set of adult lungs, and over twenty have, bearing out Janet’s argument—that the policy change was not just about Sarah.

Seven years after her transplants, Sarah continues to make impressive strides. She went back to school, jumped into swimming lessons, and even joined a competitive team. Every lung transplant patient takes things day by day, but by any standard Sarah is making the most out of her days. Her life is still not easy or simple—she takes multiple medications, goes to see her doctors regularly, and is at extremely high risk for organ rejection, as well as for strange and nasty infections. The good thing is that she no longer needs to do airway clearance, since her new lungs have normal amounts of CF protein (which is also why protein modulators won’t do her lungs any good). All things considered, a better outcome for a lung transplant patient is hard to imagine. When Dr. Goldfarb got in front of Judge Baylson and told him he believed Sarah could do very well, he was right. Her quality of life has improved immensely, one of the most important outcomes that can be hoped for. Despite all the controversy, lung transplant remains an example of the very best that we are capable of in medicine.

While the ethical issues surrounding the process have not all been resolved—fierce debate about changing the under-twelve rule continues in the lung transplant literature—one positive outcome has been the widespread press coverage for the organ, so frequently ignored, that provides the breath of life.296 As Sarah’s case makes clear, life without healthy lungs is cruel, but with them it is glorious.

In 2011, Shelley Dobson was thirty years old and had lived with cystic fibrosis every day of her life. When she came into the world, CF was with her, and when she leaves the world, its scars on her organs will be obvious. To keep her lungs healthy, Shelley has to take several inhaled medicines, usually twice a day. They go in through a nebulizer, and each dose takes ten to twenty minutes to inhale. Some of them are irritating, and result in a violent cough that can turn Shelley purple.

After inhaling the medicines, Shelley does intensive airway clearance, the most important thing. Airway clearance, as described in the previous chapter, involves some type of physical agitation, followed by deep inspiration and coughing to blast the mucus out of the chest. When Shelley was a child, her mother would pound on her back to dislodge the mucus, turning Shelley over into different positions to focus on different parts of the lung. Later, Shelley used the vibrating vest, strapping it on tightly for thirty minutes at a time.

Many CF patients are diagnosed right at birth, but Shelley wasn’t. She is African American, and CF is almost exclusively a Caucasian disease; she also had two perfectly healthy older siblings. At three months, though, her mother came home from work, and the babysitter reported that Shelley hadn’t had a wet diaper all day. Concerned about how Shelley looked, her mother brought her to the emergency room, where she was simply told Shelley’s levels of potassium and sodium were completely off. Her mother left it at that, but when this happened a second time a few months later, and then a third time, she refused to leave the ER. Shelley ended up staying in the hospital for thirty days, and was ultimately diagnosed by Dr. Howard Panitch, who would be her doctor for the next two decades.

Although her mother was told Shelley’s life expectancy was twelve years, Shelley reached the age of thirty through tenacious hard work, and around this time I became her physician. Thirty years is a long time to live with a demanding chronic illness. The burden of her therapies, of the constant struggle to keep her lungs healthy, to keep her breathing going, was starting to weigh on her.

Shelley had also complicated her life. Five years earlier, against the advice of her doctors, she had had a son, now a beautiful boy with a million-dollar smile. He was a kid who would run up to you and hug you when you walked into the room, even before you had a chance to say hello. And like all mothers, Shelley was troubled from time to time by thoughts of what her child would do without her, and also what she would do without her child. Those thoughts were becoming louder as her lungs began to show the burden of three decades of cystic fibrosis.

The biggest sign I got that something was wrong appeared on a Friday afternoon in early February. It was cold outside, and the snow and ice had built up during the Philadelphia winter. Shelley sat in the chaotic emergency room in the downtown city hospital where I worked, with machines dinging, nurses scurrying around drawing blood, and overhead pages blaring all around us.

Shelley had come in because she had been coughing up a lot of blood, not just the usual streaks in a napkin. I walked into her room and squeezed her hand. She was too tall for the hospital bed and looked awkward lying there. Her long, thin arms dangled over the railings, and an IV pole hung ominously above her, dripping in an antibiotic. She always smiled an affectionate, inviting smile, just like her son. There was no sourness in Shelley, only warmth. But today the smiles were hard to come by. She didn’t look up at me, which was unusual for her. Her husband held her hand tightly through the railing on the other side of the hospital bed as I asked the usual doctor questions: When it had started? What else, if anything, was going on—any fevers or chills, chest pain or tightness? When she responded, I could detect a hint of resignation in her voice for the first time. “Dr. Stephen,” she finally said to me, in her quiet, dignified way, the pinging of the monitors fading into the background as she spoke. “I’m really scared for one of the first times in my life. I know what I need to do, but I’m scared.”

After her diagnosis at six months of age, Shelley’s parents settled into the work of taking care of a child with a very serious illness. With the help of their doctors and team at St. Christopher’s Hospital for Children in Philadelphia, Shelley’s parents watched with wonder as their tiny baby grew slowly but surely into a typical little girl, who loved to play and get dressed up and dance and sing. Her mother helped her with her therapies, and overall she did very well. They were regimented about all the inhalers and the airway clearance, and Shelley proved wrong the doctor who predicted she wouldn’t live past twelve.

About once a year, however, Shelley found herself gripped by an acute exacerbation, something common in CF patients, which occurs when the bacteria that have chronically colonized the damaged airways multiply. The symptoms are not friendly, with fever, shortness of breath, fatigue, and weight loss knocking patients down in an instant. These bacteria must be quickly controlled, and this usually requires intravenous antibiotics for two weeks. Many CF patients suffer two or three of these episodes a year, learning to be in tune to symptoms so they can get themselves on IV antibiotics before falling off a cliff.

Starting when Shelley was ten, every March an exacerbation would send her to the hospital. Back then, CF patients could visit each other freely, and Shelley got to know the other kids with CF. They would trade music on their Walkmans, and at night put on plays for their parents, turning off the lights in the hospital room and using flashlights to illuminate their “stage.” Shelley’s mother stayed with her every night, leaving only in the morning to go to work.

In the early 1990s, two new medicines were approved for use in CF. The first of these was the inhaled antibiotic tobramycin. Doctors believed that CF patients could achieve much higher levels of effectiveness and avoid toxicity to the other organs if the medication was delivered straight to the lungs. When given too long intravenously, it created potential toxicity to the kidneys and the ear. However, this risk was obviated with the inhaled therapy, and patients could take it every day for months at a time.

The reason tobramycin was such an important medicine was that most of the patients with CF had lungs chronically colonized with a nasty bacterium, Pseudomonas aeruginosa. And like an unwelcome squatter, once Pseudomonas hit the lungs of a CF patient, it was almost impossible to eradicate. Tobramycin made no promises of eradication, but it could keep the bacterium under control. It worked as promised, and a 1997 trial showed it led to a 10 percent improvement in lung function for the average CF patient.297 Ten percent for a CF patient could mean the margin between one hospitalization a year and four, between being able to go running for half an hour or being stuck at home coughing.

The other medicine was Pulmozyme, also delivered to the lungs. Pulmozyme is not an antibiotic, but a dicer of DNA. Pseudomonas causes a massive inflammatory response, and huge numbers of white blood cells influx into the lungs to combat it. Pulmozyme works by cutting up the DNA of the dead white blood cells, effectively sweeping dead autumn leaves off the ground. This wasn’t anything fancy like gene therapy, but in a large trial it was also shown to give CF patients a modest increase in lung function.298 For Shelley, these two medicines helped stabilize her lungs. They didn’t stop the exacerbations, but they generally increased her exercise tolerance and reduced daily mucus production.

By the time Shelley entered high school, she had grown tall and beautiful, one of the tallest students in her school. The new inhaled therapies did help, but exacerbations kept coming on a yearly basis. An ominous moment occurred early in high school, when she coughed up blood for the first time. It scared her, as it would anybody, but even more because she remembered watching the movie Alex: The Life of a Child, a documentary about the life of Alex DeFord, daughter of sportswriter Frank DeFord who was also afflicted with CF. Alex coughing up blood into the white basin of a sink was an image Shelley never forgot. Alex would die at the end of the movie, all of eight years old. It was only natural Shelley believed she was on the same path, albeit a few years later in her life.

Shelley endured, finished high school, and focused on getting an advanced degree in nursing. Having cystic fibrosis and having had exacerbations, she knew the importance of nursing staff. Doctors are realistically in the room for about five minutes every day. Nurses are in and out of the room multiple times over a twelve-hour shift.

In college, Shelley met a man, Franklin, and they fell in love. He understood her, and also understood her disease. After dating for a while, they got married, and with him joining the Coast Guard, they moved from Philadelphia to Virginia. This was a big change for Shelley at age twenty-four, as her friends and family, especially her mom and dad, had been her support.

Shelley was equally nervous about being away from her doctors and transitioning into the military health system. Used to major academic medical centers, and with her persistent intermittent exacerbations, she had misgivings about her new doctors’ ability to effectively treat her. Fortunately, her misgivings were misplaced. The military doctors ended up being very good and attentive, and Shelley actually improved with her disease and was able to do something many CF physicians counseled against, believing it would be too much stress, enough to kill a woman with CF. She got pregnant.

Shelley, though, was ecstatic about her pregnancy. Always refusing to be defined by her disease, she felt having a baby was a natural progression in her life. Many old-school CF physicians would have scolded her for it, but Shelley knew her body better than anybody. With her optimism, work ethic, and support, she was quite convinced she was going to have a happy, healthy child, and that her own health would not suffer for it.

Shelley gave birth to a beautiful, happy baby boy. Her husband, Franklin, hadn’t wanted to get tested for CF, and it seemed like an okay decision. For their son, Jason, to have CF, he would have to get a CF gene from both his mother and his father. Like Shelley, Franklin was African American, and the chance that he could be a carrier of a cystic fibrosis gene was low. The carrier rate for somebody of European descent is about 1 in 29. This drops to 1 in 65 for African Americans, or about 1.5 percent of an average population. But even if Franklin did have the mutation, there was only a 50 percent chance he would pass the gene along to his son.

In the end, it wouldn’t have changed what they did. But Shelley was astounded when the doctors told her that Jason’s newborn screening test was positive for CF (newborn screening for CF began in 1995 in some states, and not until 2010 in others). It was like lightning striking twice. She experienced a barrage of emotions as she realized he would likely have to go through the same things she did—the hospitalizations, the doctors’ visits, the daily treatments. Ultimately though, the disease of CF paled in the face of what a human life meant, and she determined to keep him as healthy as she could, as her mother had done for her.

Jason did amazingly well from the start. The parallels between their lives were striking—both African Americans with CF, both doing treatments in unison, the two of them grabbing inhalers and strapping on their vibrating vests to get mucus out together.

But Shelley also noticed some very important differences. For as long as she could remember, and that included when she was young, she always had a little cough, and would bring up mucus intermittently, especially in the morning. Jason had no cough, even as he approached his sixth birthday. With the newer inhalers and vests, the disease had changed in a generation.

If things were going well for Jason, Shelley was having a rougher time. Things hadn’t worked out in Virginia, and she had separated from her husband and moved back to Philadelphia. Franklin also moved back to Philadelphia, and he remained a huge supporter of both her and Jason, but they weren’t meant to be together long term. Shelley, always driven, took up her studies to become a nurse again, but with work, cystic fibrosis, and a son—who also had CF—it was simply too much. She backed off on her studies, but still finished a degree as a medical assistant.

With so much going on, Shelley had some difficulty keeping her weight up. The exacerbations also came on worse than ever, often preceded by coughing up blood. By 2011, at the age of thirty, the antibiotics for her exacerbations were taking longer and longer to work, and instead of the usual two weeks of antibiotics, the treatment courses were stretching to three weeks.

Shelley had dealt with CF for thirty years, and despite all the treatments and doctors’ visits, CF had remained separate from her life because it had never controlled her, had never stopped her from doing anything. Now, with the increased exacerbations, the blood coming up, the time in the hospital, her life was spiraling downward like never before. During this time, I would see Shelley in the emergency room at the hospital, each time a little sicker, coughing up a little more blood, and a little more frustrated than before.

In 2011, at our CF center in Philadelphia, we were hearing rumblings about new medicines on the horizon, protein modulators that could radically change how we treated cystic fibrosis. We also knew that only certain patients would qualify, and we would have to know all of our patient’s genetic mutations to see if they were eligible.

Prior to the advent of protein modulators, an individual patient’s genetic mutations had been an afterthought. CF was diagnosed with the sweat test, and knowing a patient’s mutations was somewhat interesting but not essential. With the modulators on the horizon, a hunt went on in CF clinics throughout the world to determine which patients had which gene defects. Over one week in September 2011, I began each morning by pulling a few charts at a time from the bookcase housing the files of our some hundred patients, searching for elusive pieces of paper from five, ten, or even fifteen years before that told us which mutations each patient possessed.

The majority of the charts contained the information, usually on a faded yellow sheet of paper with an old type font. I put the patients’ names and their mutations into a spreadsheet on my computer. When I saved the document, I saw that it took up twenty-five kilobytes of memory—a miniscule amount of space. But this spreadsheet was perhaps the most important document on my computer. It would soon dictate what medicines certain patients would be able to try.

Ivacaftor, the new drug from Vertex Pharmaceuticals, was approved by the FDA for use in patients with the G551D mutation on January 31, 2012. At my university, we did what hundreds of centers throughout the world were doing, checking our database to find which patients held this mutation. We had four, the precise number of patients predicted by statistics. And one of them was Shelley.

The medicine was so new, our computer system didn’t have it in its database yet. So we found an old-fashioned paper prescription pad and I wrote out four prescriptions in long hand, one for each of our four patients with the matching mutation. When we saw Shelley in the clinic, I noted how she carefully folded it and put it in her purse.

We handed out the other three prescriptions, and we crossed our fingers that something good was going to happen. A month passed, and to our delight some extraordinary stories started filtering in. One CF patient told us about her dry mouth. For some reason CF had affected her salivary glands, and her mouth was chronically dry and cracked. She constantly popped hard candy to stimulate her glands. After her first dose of ivacaftor, she noticed a strange sensation on her tongue and in her cheeks. At first, she didn’t recognize her own spit because it had been so long since she had produced any. She was so overtaken with joy, just to experience something normal like that again, that she started crying.

Other stories came in reporting that the medicine didn’t just work on the CFTR protein in the lung, it worked everywhere in the body, including the pancreas and gastrointestinal tract. One of our patients had this good fortune. Not only did his lung function improve, but his scarred pancreas began working and he was able to stop taking his pancreatic enzymes before meals. For the first time, he was able to just sit down, eat, and digest as we all do. He was also able to get off his inhaled antibiotic, creating an extra half hour in his mornings and evenings.

For some reason, Shelley did not have any dramatic stories to tell, probably because her attitude was so positive to begin with. There is no negativity in her to combat, no suppressed demons. She always tells you how she feels and focuses on the positives in her life, her beautiful son, her work. She is so even-keeled that nothing could radically change her outlook. Not even ivacaftor could do that.

Eventually, though, as the months passed, the changes became noticeable. Shelley stopped coughing up blood, and her lung function crept up, along with her weight. The exacerbations ended, and when we saw her in clinic, the conversations were short, whereas before she had lingered to talk about this symptom or that issue.

Her son, Jason, was also able to go on ivacaftor. At conception, Shelley had given him only one of the two genes for CF, but we found out later she gave him the one that was now treatable. She told me they always took their pills together, every morning and every evening, a family ritual that bonded them even more tightly together. Having a pill that helps ease the burden of disease was something that every CF patient, every parent, had dreamed of when they first got their diagnosis of cystic fibrosis. Now Shelley got to do it for herself and her child. Personalized medicine had arrived on Shelley’s doorstep, and just in time.

Other patients afflicted with cystic fibrosis have not been as lucky as Shelley. A few in our center passed away just prior to the availability of protein modulators, and more than a few over the decades prior. Others, like Sarah Murnaghan, have needed to undergo lung transplant and deal with the daily uncertainty that comes with chronic immune suppression. It is a horrible, deadly disease that robs children of their youth, and families of their offspring. But the spirit of investigation has transformed it from something unknown to something known, something untreatable to something treatable. And now, finally, to something on the cusp of being cured. Patients like Shelley, living longer, happier, and healthier, are becoming the norm, not the exception. The breath restored is indeed something magnificent.

285. Janet Murnaghan, Saving Sarah: One Mother’s Battle Against the Health Care System to Save Her Daughter’s Life (New York: St. Martin’s Press, 2018).

286. https://www.foxnews.com/us/case-of-dying-10-year-old-prompts-federal-call-for-review-of-child-organ-transplant-rules.

287. US Department of Health and Human Services, “Organ Procurement and Transplantation Network, National Data,” Organ Procurement and Transplantation Network website, https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#.

288. Thomas M. Egan and Leah B. Edwards, “Effect of the Lung Allocation Score on Lung Transplantation in the United States,” Journal of Heart and Lung Transplantations 35, no. 4 (April 2016): 433–439.

289. Karen Ladin and Douglas W. Hanto, “Rationing Lung Transplants—Procedural Fairness in Allocation and Appeals,” New England Journal of Medicine 369, no. 7 (August 15, 2013): 599–601.

290. Janet Murnaghan, Saving Sarah: One Mother’s Battle Against the Health Care System to Save Her Daughter’s Life (New York: St. Martin’s Press, 2018).

291. Chris Welch and Zain Asher, “With Just Weeks Left, Sarah Fights the System for Life-­Saving Pair of Lungs,” CNN Online, May 27, 2013, https://www.cnn.com/2013/05/27/health/pennsylvania-girl-lungs/index.html.

292. Chris Welch and Zain Asher, “With Just Weeks Left, Sarah Fights the System for Life-­Saving Pair of Lungs,” CNN Online, May 27, 2013, https://www.cnn .com/2013/05/27/health/pennsylvania-girl-lungs/index.html.

293. Brett Norman and Jason Millman, “Sebelius Ordered to Make Exception on Transplant,” Politico, June 5, 2013, https://www.politico.com/story/2013/06/sarah-murnaghan-lung-transplant-ruling-kathleen-sebelius-092299.

294. Howard Panitch, e-mail message to the author with transcript of speech, October 3, 2014.

295. Sarah Murnaghan, “Acceptance Speech for Shining Star Award,” (meeting of the Cystic Fibrosis Foundation, Philadelphia, PA, February 2014).

296. J. deSante, A. Caplan, B. Hippen, et al., “Was Sarah Murnaghan Treated Justly?” Pediatrics 134, no. 1 (July 2014): 155–162.

297. Bonnie W. Ramsey, Margaret S. Pepe, Joanne M. Quan, et al., “Intermittent Administration of Inhaled Tobramycin in Patients with Cystic Fibrosis,” New England Journal of Medicine 340 (January 7, 1999): 23–30.

298. Henry J. Fuchs, Drucy S. Borowitz, David H. Christiansen, et al., “Effect of Aerosolized Recombinant Human DNase on Exacerbations of Respiratory Symptoms and on Pulmonary Function in Patients with Cystic Fibrosis,” New England Journal of Medicine 331 (September 8, 1994): 637–642.