A box of cystic fibrosis medicine Trikafta. Photo / Dado Galdieri, The New York Times
OPINION:
Imagine if you knew, from your earliest awareness, that you were unlikely to live beyond your 20s. You would finish high school, but what about college? Would you allow yourself to fall in love? How much would you invest in a future that you might never see?
When Molly Pam was born in 1988, these impossible questions were the reality for people with cystic fibrosis, a genetic disease that leads to an early death from lung failure. But Pam is now 34. And thanks to a new drug that has revolutionised the treatment of this disease, she will likely live to celebrate her 40th and even 50th birthdays. Her life expectancy has shifted drastically within her lifetime.
It is a remarkable and complicated experience. And as science races forward with gene therapy and targeted cancer treatments that promise to turn terminal disease into chronic illness, it is also a lesson in what might be ahead.
Pam was diagnosed with cystic fibrosis a few weeks before she turned 10. As a middle schooler, she went on a deep dive — discovering the memoir of a man with the disease who was amazed to live past 25. Was this what awaited her? Even though she followed her family legacy and went to college at Stanford, then moved to Manhattan, that question lingered.
As did the reality of her limited lung function. Early on after college, she realised that her body would not sustain full-time work. Still, she was able to build a life. She went to culinary school and built a career as a freelance chef. She fell in love and married.
Then, as she approached her 30th birthday, everything started to unravel. Her lung function plunged under multiple drug-resistant infections and eventual lung collapse. She stopped working and moved to California so that she and her husband could be near her family and her sister’s children. They would not have children of their own, that much was clear. The evaluation for a lung transplant began.
But as she prepared herself for the possibility of a transplant, Pam started on a new drug therapy that targets the underlying cause of her disease. And now, three years later, she is healthier than she had been in years. Her lung function has doubled. Possibility expands once again.
Since its approval in 2019, the drug therapy, Trikafta, has been heralded as a game changer for a majority of those with cystic fibrosis. The disease is caused by defects in a protein that affects the body’s cells and tissues, leading to mucus that accumulates in the lungs and other organs. Trikafta, a combination of three drugs, helps the faulty protein function more effectively. Without the thick mucus and infections and scarring that come with it, patients can ideally avoid the inevitable respiratory decline that characterises life with C.F.
Some people have genetic mutations that do not allow them to benefit from Trikafta, which targets the most common C.F. mutation. Still, many of those born with the disease today can expect to live into their 60s — a prognosis that will most likely continue to improve during their lifetimes. They will grow up with an entirely different outlook, with a disease that for many will be chronic and manageable. But for those who are Pam’s age or older, many of whom have made decisions about career and family based on the expectation of a shortened life span, this staggering scientific advance has left them facing existential questions.
One woman in her 40s with cystic fibrosis withdrew her retirement money some years back to “live in the moment,” she said, because she assumed she would die before any traditional retirement. She is alive now, but she is adrift. There are others who never went to college or planned for a career because they and their parents believed that their health would make such a decision unnecessary. Internalising the prognosis they had at birth, they never invested in adulthood, and yet here they are, adults, with years in front of them. Those who were sick enough before Trikafta to find themselves on the verge of transplant have been pulled back from the brink. But now what? And can they trust that this reprieve will last?
“Many patients are continuing to adjust to the impact of this transformative era on their lives,” said Dr Manuela Cernadas, a pulmonologist who specialises in cystic fibrosis at Boston Children’s Hospital and Brigham and Women’s Hospital, where I work. Even as she celebrates the improving pulmonary function that so many of her patients have enjoyed since starting Trikafta, she thinks of the patients who died just before the drug was approved or who received lung transplants only to die nonetheless. They were so close, but there is so much randomness to this kind of luck, so many what-ifs. Dr Cernadas is aware, too, that none of this is simple for patients who have lived their lives under the shadow of an early death.
“It’s a tremendous blessing for most patients, but it can also be a source of anxiety,” Dr Cernadas noted. “You had this thought of how your life would play out. It’s what you prepared for. But now you’re going to live a lot longer. It can be a lot to go through, a lot to process. What are you going to do with that time?”
For some, the answer is to commit fully to the future and even to rethink prior decisions about family. Trikafta may increase fertility, and women who long ago stopped using contraception are now finding themselves pregnant — and healthy enough to safely carry those pregnancies. It is a sort of awakening, bodies functioning as they never had. Doctors are seeing an increase in planned pregnancy, too, in those who long ago decided that they should not or could not have children but now realise that there is still time and this is one thing they don’t want to regret.
There are other choices, small but poignant acts of hope. One cystic fibrosis specialist told me about a patient in her 40s who finally decided to get braces to straighten crooked teeth and another who was planning a long-delayed cosmetic procedure on her eyes. As we talked, I found myself thinking of a young woman with C.F. I met some years ago. She told me that there was a point when she had decided to start wearing sunscreen, thinking that perhaps she would live long enough for sun damage to matter after all.
One doctor called this generation of C.F. patients, those in their 30s and 40s and even 50s, a “transition generation.” Many of those who are younger will never know what it was like for them in their early years, when they were told they might not live past 30. Those who already had lung transplants can watch this change from the sidelines but will probably not see direct benefit from it. There is so much we do not yet know. How will the disease progress for those on Trikafta? What happens to those on disability, who are healthier now but perhaps not healthy enough to return to full-time work? What therapies will come next, and will competitor drugs ultimately lower Trikafta’s high cost and make this treatment accessible to people in low- and middle-income countries? But the here and now is something remarkable.
These days, Pam is simply excited to experience a life that once seemed impossible. She has returned to long-distance hiking and marvels at how well she can breathe. When the winter comes, she gets on the slopes, and with the aid of supplemental oxygen, she is able to return to a sport she last enjoyed in high school. Her lung function continues to improve, better at each clinic visit. And perhaps most powerfully, she and her husband are thinking about starting a family. She dreams about a house near her sister, where they can live in a sort of family compound, raising their children together. It will not be easy, and none of it is definite, but there is hope and life to live.
“What is my life like?” Pam asked. “If you’d asked me three years ago, I wouldn’t have dreamed of how amazing it would be and how lucky I am to be able to think so far in the future. There are questions. But we’re living it. We’re the research.”
This article originally appeared in The New York Times.
Written by: Daniela J. Lamas
Photographs by: Dado Galdieri
©2023 THE NEW YORK TIMES
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