You could say that Jessie had been sick since before she was born. A bowel obstruction detected on her mother’s ultrasound led the obstetrician to surmise the baby was likely to have cystic fibrosis, a genetic illness that impairs breathing and digestion.
A day after birth, Jessie underwent bowel surgery and a week later, in late fall 1988, her parents, Rich and Susan Ulan, took her home, unsure what to expect. They’d read troubling, outdated articles that said children with cystic fibrosis lived only 12 years.
In fact, the median predicted age of survival was 27 when Jessie was born, and the forecasts improved over the years.
Still, by the time she reached her 20s, she was gasping for air every morning, required hours of daily therapy, took dozens of medications, and still ended up in the hospital again and again. Rich and Susan started to worry that they would soon lose their daughter.
But then came the blue and pink pills. As she recorded the moment on her phone, Jessie had no idea what would happen next. Would this longed-for gift deliver on its promise? And if it did, what would it feel like to suddenly see the future stretching to a distant horizon?
Her daughter Eva, then 3, stood at her side that evening in November 2019, as Jessie picked up the first pill and lifted a glass of milk. “Here goes nothing,” she said.
For centuries, an old wives’ tale held that if you kissed your baby and tasted salt, the baby would soon die. The tale may have been the first reference to cystic fibrosis, even though the disease was unknown for most of history. People with CF do indeed have salty sweat — the result of cells’ inability to manage the flow of water and salt.
And those salty babies did die. At the time cystic fibrosis was first recognized in 1938, the old wisdom was correct — the majority of CF babies, malnourished despite the best efforts to feed them, didn’t survive their first year.
As research in later decades discovered, CF causes mucus to become thick and tarlike, instead of the slippery coating that, in healthy people, lubricates and protects the organs.
How cystic fibrosis affects the lungs
The most devastating effects occur in the lungs. The tiny hairs needed to clear the airways can’t sweep back and forth, and a cornucopia of bacteria flourishes in the lungs’ clogged recesses.
Cystic fibrosis is the most common genetic disease among Caucasians, although it can affect every racial or ethnic group. But it is still quite rare, occurring in roughly one in every 5,000 births in the United States.
When the Ulans brought baby Jessie home to Westfield, science had yet to yield a treatment for the underlying cause of CF. But the parents did have an armload of tools to counteract its effects.
Their child’s pancreas, ravaged before birth, could no longer produce digestive enzymes, so medicine would substitute. Sue broke open capsules, sprinkled the beads on applesauce, and spooned it into Jessie’s reluctant mouth.
Physiotherapy loosens the mucus in the lungs: Sue held a small rubber device between her fingers and pounded the baby’s chest with its cupped end. Front, back, and sides for 20 minutes, twice a day. When Jessica got bigger, Sue would do this with her cupped hand.
The Ulans got to be pros at these therapies. They took their chances on a second pregnancy, because a child gets CF only if it inherits the gene from both parents. That meant each pregnancy had a 75 percent chance of producing a healthy child. Joshua was born in 1991, also needing surgery for a bowel obstruction, also bearing two copies of the fatal gene. Two years later, a birth control failure brought them Rebekkah, known as Becky, and she didn’t beat the odds either.
It was a lot of work, caring for three kids with a demanding, chronic illness, but in some ways, Sue says, having three with CF was no harder than raising one or two. All followed the same routines. Morning and night Sue and Rich handed out their pills; they went from one to the other to drum their chests before bed. The kids called this therapy “thumps” and found it relaxing.
When she thinks back on those days, Sue remembers the sounds. The plop-plop of her hand on their backs, the grinding of the vibrating vests that later supplemented hands-on therapy, the roar of the nebulizer that infused medications and saline mist into their lungs.
And the cough. Oh, that CF cough — a whole-body cataclysm of hacking and gagging.
After the couple divorced in 2000, Rich remained part of their lives — but Sue would handle the nights alone. Sometimes the kids would all be coughing at once, and she’d lie in bed sleepless with worry.
Worry afflicted the whole family. All of her children, Sue said, have suffered from anxiety and depression throughout their lives, as is common in people with CF. The mental health toll of forever “living under the sword,” she said, has been severe.
Even so, the Ulan siblings describe their childhoods as normal, even healthy, most of the time. Sue encouraged them to sign up for sports and dance classes, and never thought twice about sending them to sleepovers.
Jessie said that, as a child, the only difference she saw between herself and her friends was that she took pills and they didn’t. Of course as she got a little older, she had to haul her vibrating vest and nebulizer to sleepovers, if she didn’t want to spend the night coughing.
“We were always raised that we were no different than anybody else,” Jessie said, with gratitude.
And the likelihood that she would die young? Her parents never mentioned it.
For Rich and Susan, the knowledge that they would outlive their children pervaded their lives like the scent of a distant fire. But at the same time, Rich said, he saw that life expectancy estimates increased each year, and he knew research was progressing, so he tried to “stay positive.”
Sue considered it paramount that her children grow up without feeling that they had an “expiration date.” She figured that if they had questions when they got older, she would answer them.
Instead, they turned to the internet. In their early teens, Jessie and Becky did some online research about CF. They read that their life expectancy was in the 30s but said that did not worry them. “You’re a kid. You’re like, ha-ha, sounds like forever,” Jessie said.
Around the time the Ulan sisters were browsing for facts about their illness, a CF research revolution was getting under way. A company in San Diego decided to take a chance on beating this chronic killer and in 2001 turned to a scientist named Fred Van Goor, a Canadian who once studied goldfish reproduction. When he took the job, Van Goor knew little about the disease, but he joined Paul Negulescu and Sabine Hadida as the company, which was bought by Vertex Pharmaceuticals, sought a solution for cystic fibrosis. Twelve years had passed since the CF gene was identified; a breakthrough was overdue.
Van Goor’s team started exploring a novel idea: a medication that would fix the faulty protein that underlies the illness.
In a normal cell, a tube-like protein opens a channel for chloride, a component of salt, to rise to the surface. There the chloride attracts water and keeps membranes pliable and moist.
In people with CF, the protein that escorts and releases chloride is missing or malformed. Chloride has no way out, and water is not drawn to the cell’s surface. Mucus becomes too dry and thickens.
With funding from the Cystic Fibrosis Foundation, Van Goor’s team was testing a medication that opened the chloride channels at the cell’s surface.
They knew from the get-go that, if this worked, it would help only a tiny percentage of CF sufferers, those with a rare mutation in which the protein reaches the cell surface but doesn’t work once it’s there. They hoped it would prove that it was possible to repair the protein — and point the way to treatments for a wider group of people.
A group of 39 patients participated in a four-week study of the new substance. And in 2008, about a dozen Vertex executives gathered around a conference table at Vertex’s old headquarters in Cambridge to view the results.
Van Goor happened to be in town and stopped in. He says he’ll never forget the stunned silence that fell as a team member displayed one slide after another. The goal had been to slow the deterioration of patients’ lungs. But the numbers showed that the new drug did much more: Participants’ lungs got dramatically better. “There wasn’t a dry eye in the room,” he recalled recently. “Everybody was just so taken aback by that result.”
After further studies backed up the initial findings, the FDA approved the drug, named Kalydeco, in 2012. But it helped only 4 percent of CF patients. That didn’t include any of the Ulan siblings, who share the most common CF mutation, known as f508del.
Still Kalydeco was revolutionary: It showed that it’s possible to restore the function of a protein that had been rendered useless by a genetic mutation. It was the first drug ever to correct the root cause of a genetic disease.
The CF research had been a small part of Vertex’s portfolio. But Kalydeco’s promise lit a fire and the company boosted its investment.
“Now we knew we needed to do this for everybody,” Van Goor said.
The Ulan siblings’ young lives overlapped this period of research, from the discovery of the CF gene in 1989 to the development of protein-repairing medicines by Van Goor and others — a class of drugs known as “modulators.” The kids didn’t track the details but do remember people applauding when the latest research updates were showcased at each of the golf tournaments that Rich organized to raise money for the Cystic Fibrosis Foundation.
But they don’t recall giving much thought to how any of that work might affect their own lives. Instead, they moved through life, never knowing when the next health crisis would occur, focusing on accomplishing, in the time they had, whatever was most important to them.
Jessie went to college for a semester and a half, but quit to marry Keith Anderson, whom she met at the company where they both worked, a place that sells and installs swimming pools. Thinking “my life’s on the fast lane here,” she saw a choice between pursuing school or pursuing a relationship, and chose the latter. She most wanted to be a wife and mom.
Josh, who had hated being a sickly, skinny kid, conquered that fate at the gym, adding 70 pounds of muscle to his 5-foot-11 frame in the years after high school. He co-owned a gym till the pandemic and now works as an online personal trainer.
Becky followed her dream of becoming a hairdresser, a job she loves because she helps people feel good about themselves. She married Michael Jazab, a friend of Jessie’s husband, in 2016.
Jessie was always the sickest of the three and by her late teens it was clear her lungs were weakening. From time to time, the ever-simmering infections flared up, causing fevers and breathlessness, and she headed to the hospital for a few days of antibiotic infusions.
She was already struggling with her health, her hospital visits becoming more frequent, when she and Keith had married in 2012.
Shortly before the wedding, Jessie’s doctor pulled Keith aside to ask if he knew what he was getting into. The doctor’s words appalled the Ulans; it felt like he thought a person with a chronic illness didn’t have a right to fall in love and have a family.
They soon found another doctor.
Keith says he certainly knew what he was getting into. They’d been dating for four years, and he had seen what CF did to Jessie. But they didn’t talk about what Keith called “the negative outcomes.”
“We just went through life, and things were good,” he said. “Then things progressed over time.”
Jessie had always yearned to be a mother, and eventually she got her wish. CF occurs only when both parents carry the gene mutation, and although Keith was never tested, the odds were low that their child would be affected. And, in the beginning, Jessie didn’t contemplate that she might not see that child reach adulthood.
“I felt like I had a lot of love to give,” she said. “And I loved Keith and I wanted, you know, that little family.”
But CF makes it hard for women to get pregnant, and it took three rounds of infertility treatment for Jessie. In 2016, she gave birth to Eva, naming her after Eva Markvoort, a Canadian blogger and advocate with CF who died in 2010 at age 25.
Pregnancy strained Jessie’s body. Motherhood, too. She remembers being up all night with Eva, and then in the morning, her cough would start up. To avoid waking the baby, she’d rush to the bathroom to press a towel over her mouth.
By the time Eva was 2, Jessie — then almost 30 — was in the hospital for 10 to 14 days at a time almost every month. She spent so much time in the hospital that she decorated her room to feel like home.
She needed to nap every day. Just walking up a flight of stairs would land her on her back for five or 10 minutes, trying to catch her breath. “We were going down a really bad road,” Jessie said, “where no matter what I did, and medications I took, it was just not making a difference.”
She focused on her next treatment, her next doctor’s visit. The all-consuming task of managing her health left little time to contemplate the future. But sometimes, lying in bed struggling to breathe, Jessie would think, “Well, this is going to be the rest of my life. … It’s like drowning from the inside out, the way you die. And that’s definitely scary.”
Through it all, she always had her sister. And for added support amid such fears, Jessie could turn to an online community of CF patients. But she could never meet them, go out to lunch with them, share hugs with them. Each CF patient harbors different microbes in their lungs and if they get within six feet of each other, they might inhale germs their bodies are unaccustomed to, with dire consequences. That means no CF summer camps for kids, no in-person support groups.
Growing up in the same household, though, the three Ulan siblings shared not only CF but the same germs, and they formed a deep bond.
Becky and Jessie are close as sisters can be. They text constantly and see each other nearly every day.
But they come across as very different people. Jessie is slender and lithe with sleek blond hair down her back, a thin gold nose ring, and elegant, melancholic features. Becky, with a round face and a couple of silver rings sparkling in her nose, has a perky, chatty manner that contrasts with her sister’s reserve. She dyes her naturally blond hair black with coppery spikes.
Once when Eva was little, Jessie and Becky went to a 15th birthday party for a friend’s daughter. As they watched the daughter dance with her mother, it struck them that Jessie might not be alive for her own daughter’s 15th birthday. The sisters fell into each other’s arms, sobbing.
In those days, Jessie’s doctor was starting to talk about a major step she could take to extend her life: a lung transplant.
But when she went to see him in the summer of 2019, J. Samuel Pope raised an entirely different topic: an exciting new drug that was awaiting FDA approval.
After the success of Kalydeco, Vertex had developed other drugs that corrected the malfunctioning proteins that lead to cystic fibrosis, and now it had hit upon an especially promising combination of three “modulator” drugs, called Trikafta.
A couple of Pope’s patients had taken Trikafta as participants in the clinical trial, and the results were stunning — as with most study participants, their lungs improved and they were much less likely to need hospital care or IV antibiotics.
With his soothing Southern accent and calm demeanor, Pope had eased Jessie through many a health crisis, and she adored him. Now, though, she was skeptical. She had picked up the buzz about Trikafta in her social media groups, but she’d already tried so many medications that didn’t make much difference.
“Yep,” she scoffed, “a miracle drug.”
Pope looked her in the eye and said: “This is your miracle drug.”
Just about everyone affected by cystic fibrosis can tell you where they were on Oct. 21, 2019, the day when — months sooner than expected — the Food and Drug Administration approved Trikafta. As the news got out, phones dinged and buzzed throughout the CF community. Parents wept with joy.
Within a few weeks, Jessie’s birthday box of Trikafta arrived. Soon she experienced what Trikafta patients call “the purge.” As the cells start allowing salt to the surface, mucus loosens up throughout the body. It needs to come out, an unlovely and unpleasant process that involves several days of coughing.
About a week later, Jessie woke up one day and realized she no longer felt like someone was sitting on her chest. She didn’t urgently need to grab her nebulizer and don her vibrating vest. She could breathe.
A few weeks after that, Jessie was in her room, following her usual work-out routine with an online program, when she noticed a striking change. “I got this burn in my lungs that I used to feel when I played soccer when I was a kid. And that was just like the best feeling ever. I could push myself further and further.”
And then, a shocker — pregnancy. She wasn’t planning on it, at least not so fast. She and Keith had wanted a second child, but planned to wait out the changes from Trikafta and consult her doctor. Instead, it happened within weeks of starting the new medication.
It happened to a lot of women. Trikafta hasn’t been tested in pregnant women, and the drugmaker suggests that women consult their doctors before trying to get pregnant. But some wanted children badly and others were caught off guard, unaware that Trikafta would make them suddenly more fertile. The number of pregnancies among women with CF more than doubled between 2018 and 2022. A generation of “Trikafta babies” was born.
Jessie called Becky to share her news. Becky had just lost a pregnancy, after a third round of costly infertility treatments, and was devastated. She couldn’t celebrate Jessie’s news. Instead, Becky ended the conversation quickly and barely spoke to her sister for weeks.
Becky got her Trikafta box in February 2020. She brought the pills to the salon where she works and announced to all that she was about to take her “miracle medicine.” A few hours later, as she was shampooing her last client of the day, she rushed to the bathroom trying to muffle an intense coughing fit. The whole salon heard it, aghast.
Becky apologized and assured them she was fine. A little earlier than expected, the purge had begun.
Within days, she was breathing easily and full of energy. “I feel amazing,” she wrote in a text. “It gets better every day.”
And then, a few weeks after Becky took her first dose of Trikafta, she took a pregnancy test. It showed two lines. After all she’d been through, she didn’t dare believe it — not until she saw her first ultrasound at seven weeks. In the interim, Becky took 56 pregnancy tests.
Trikafta is a life-changing drug, but not for all. It works in just over 90 percent of CF patients. The rest have rare mutations that don’t respond.
Those who have these rare mutations are more likely to be Hispanic or Black. About 30 percent of Blacks and a quarter of Hispanics with CF are ineligible for Trikafta, compared with just a tenth of whites, according to a recent analysis.
Amid its triumph with Trikafta, Vertex faced criticism for pricing the drug at $311,000 a year. The Institute for Clinical and Economic Review, which analyzes the value of medical interventions, determined that Trikafta was worth only $67,900 to $85,500 per year.
But Vertex officials said a drug that extends young lives was well worth the cost. Insurers and government programs have mostly been covering it, although some patients have lately faced new costs and struggles obtaining coverage. Trikafta has proven to be a blockbuster for Vertex, whose total profits reached $8.9 billion in 2022.
Meanwhile, the good news about Trikafta’s effects continues to pour in. In June 2022, Vertex released data showing dramatic reductions in lung-infection flare-ups and death among those taking the drug. Then in June of this year, the company reported that the benefits aren’t waning: People who took Trikafta experienced no decline in lung function over four years.
Lung transplants, once a last-ditch life-saver, are starting to become uncommon. Among the 32,621 CF patients tracked by the Cystic Fibrosis Foundation’s registry, only 53 underwent lung transplants in 2022, compared with 250 in 2017.
“It’s been truly miraculous,” said Pope, Jessie’s doctor, who is director of the adult cystic fibrosis program at Hartford Hospital. “We used to have five to seven patients at any one time in the hospital. Now it’s one or two a year.”
Dr. Ahmet Uluer, a lung specialist with the Boston Children’s Hospital and Brigham and Women’s Hospital CF center — and Becky’s doctor — said his patients became so healthy that he had to lay off staff and take on additional responsibilities caring for adults with chronic and congenital illnesses.
Even before Trikafta came along, the number of people with CF rose 25 percent in a decade, to 40,000, because improvements in care has prolonged people’s lives. CF was once primarily a pediatric disease, but today 60 percent of patients are adults.
Now it is estimated that half the people with CF born between 2018 and 2022 will live 56 years or longer (up from 38 a decade earlier).
Trikafta is too new for its effects on life expectancy to be measured. But there’s every reason for people taking the drug to expect a longer life, perhaps a normal lifespan. Death no longer looms so close.
And that’s the kind of good news that comes with complications.
In the 1990s, people who were dying of AIDS gave away their possessions and bought their tombstones. Then, new drug regimens restored their health, and they had to figure out how to resume living.
For people with cystic fibrosis, the upheaval spurred by those blue and pink pills proved to be even more disorienting. They felt better, but lost a central part of their identity — having a chronic illness. They also confronted unfamiliar worries: Careers. Money. Old age.
Uluer calls it “the existential threat of living.” Many of his patients felt lost.
Jessie and Becky felt the same way.
“You’ve kind of grown up to know that you were going to die at a young age. ... And then all of a sudden someone’s like, ‘Well, hey, you’re gonna live a regular life now,’” Jessie said. “It’s hard mentally — it’s like your CF was your identity for such a long time and now it’s not.”
Both sisters say they have long suffered from depression — and Trikafta has worsened it. They are not alone. Doctors are noticing mental health troubles among Trikafta patients, as well as brain fogginess and memory issues. The proteins that Trikafta targets are found in the brain, but even so it’s not clear that the drug is the culprit. It’s hard to separate its effects from everything else going on in a person’s life.
As Jessie sees it, she has always been sad, and with Trikafta she’s sadder, but that’s a small price to be able to breathe. Still, she is dogged by guilt. Guilt over friends who died before the drug came out, friends who don’t qualify for it or couldn’t tolerate it. Guilt for not feeling more appreciative of her newfound health.
Becky puts it this way: “You’re so grateful to be healthy. It’s amazing, but it’s also this most foreign thing. It’s almost like you don’t know who you are anymore. Who am I outside of CF? Who, what, who is this person?”
“Sometimes,” Becky said, “living feels like the scary thing.”
Back in February 2020, Jessie and her mother, Sue, came to visit Becky at her brick ranch house in Chicopee. They talked about how strange it felt to experience health.
As she spoke, Becky was half-sitting, half-reclining, leaning comfortably against her mother on the couch — a posture that before Trikafta would have induced a coughing fit.
And that’s when Becky mentioned another side effect from taking Trikafta: The siblings realized that instead of dying young, they may have to cope with the deaths of people they love.
“We never really had to worry,” she said, “that we would have to face loss.”
A couple of weeks later, sooner than they ever imagined, they did.
It was a chilly day in March 2020 when Sue came to deliver the news. Jessie remembers sitting on the little heater in her living room, with Josh across from her on the couch, in the mansard-roofed house in the middle of a sloping lawn, the house they grew up in.
The other thing Jessie remembers is how angry she felt, an anger that hasn’t dissipated in the years since.
Sue told them she had just gotten the results of a breast biopsy. It showed that she had cancer.
“I yelled at her,” Jessie said, feeling bad about it now. She was furious at her mom for neglecting her health by ignoring a growing lump for some time. Soon they would learn that the cancer had already spread to her lungs.
Becky got the news from Sue in a phone call while driving to work. She kept driving even as tears poured down her face. She had never imagined a life without her mom.
Suddenly, Sue had traded places with her children. They learned the anguish of having a loved one who is sick — and found it much harder to deal with than their own disease.
Jessie even said, “I’d rather be the one who died.”
For all its transformative powers, Trikafta does not erase CF, or undo all the damage it caused. Jessie, for instance, continues to take several medications to keep her lungs open and her digestive system functioning.
But those born today face brighter prospects. Trikafta is now approved for children as young as 2, and Vertex is studying its safety in even littler ones. These youngsters may escape most of CF’s wreckage, a transformation so dramatic that, starting next year, children with CF will no longer automatically qualify for a wish through the Make-a-Wish Foundation.
The drug is not without its problems, however. Social media among CF patients sizzles with tales of Trikafta side effects, everything from acne to stomach pain to memory loss, in addition to depression and anxiety. Some people have adjusted their doses, but very few have had to give it up altogether. Vertex attributes these symptoms to preexisting health issues and says it hasn’t found any side effect beyond those identified in the clinical trials, which range from rare liver trouble to headaches.
A common consequence of Trikafta use is weight gain, for better or worse. CF keeps the body in a constant inflammatory state that incinerates calories, and CF patients grow up struggling to pack in enough high-fat foods to sustain them. On Trikafta, the metabolism calms down, and among all the other changes, now people have to learn a new way of eating.
Jessie has gained about 20 pounds, but her longtime devotion to exercise has kept her looking fit. Becky is working with a personal trainer provided by a charity. Like most people taking Trikafta, they have to watch what they eat as never before.
What does the future hold? “It’s a very weird question, the future,” Jessie said.
Had she known she was going to live a longer life, she might have stayed in college, to study art or writing, something creative.
“Looking back now, it’s like, I probably would have liked to do a career,” she said. Now she has a toddler, black-haired Ivy, along with Eva, a high-maintenance spitfire who turns 7 this month — and her days are filled with their care.
Becky’s future came into sharper focus when she learned that the child she conceived right after taking Trikafta, her beloved son Frankie, has autism. “My mission for the rest of my life,” Becky said, “is just to help him and work with him.”
Jessie’s daughter Eva was diagnosed with autism earlier this year. Now the sisters, Jessie said, “live a very similar life with similar struggles. We’re like the same person.”
Life is still throwing up obstacles, but also the occasional surprise. Last fall, Becky learned that she’d been awarded a “wellness” grant from a charity for CF patients based at Brigham and Women’s Hospital. It was intended to give her a chance to travel, and she could bring her siblings along.
Jessie, Josh, and Becky flew to Los Angeles to attend a concert by their favorite performer, the singer Post Malone. Such a trip would have been unthinkable three years earlier, but now they happily toured Hollywood and Venice Beach, unencumbered by treatment paraphernalia or health worries. At the concert, they had seats near the front, got Malone’s signature, and exulted in two hours of dancing in the pit, a once-unimaginable pleasure.
“It was probably the most magical day on earth,” Jessie said.
The expedition offered a sorely needed respite. Right before the trip, Becky had received her son’s diagnosis. Their mother, Sue, who’d been successfully beating back her cancer for many months, had just found another tumor.
And so their joys and sorrows mingle, unstopping, as long as life continues.