Breakfast in the Snow

Revisiting | Breakfast in the Snow

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Francis Collins: [singing a capella] Dare to dream, dare to dream, all our brothers and sisters breathing free. Unafraid, our hopes unswayed, till the story of CF is history.

Katie Hafner: I’m Katie Hafner and this is Lost Women of Science, a podcast in which we unearth stories of female scientists who didn’t receive the recognition they deserved. We devote each season to the life and work of one woman. We’re revisiting the historical record, one extraordinary scientist at a time. 

This is the final episode of our first season, “The Pathologist in the Basement.” We’ve been telling the story of Dr. Dorothy Andersen, a physician who was the first to identify the disease cystic fibrosis in the 1930s. 

This episode is divided into two parts. One of those parts is linked to that voice you just heard singing. It belongs to Dr. Francis Collins, the outgoing director of the NIH. Dr. Collins is one of the geneticists who isolated the cystic fibrosis gene in 1989. In this episode, we’ll explore advances in CF treatment. And we’ll also explore Dorothy Andersen’s legacy, starting at the end of her life. 

The last living keeper of that legacy is Dr. Celia Ores, a pediatrician mentored by Dr. Andersen in the early 1960s.

Celia Ores: Can you put this down and we go and pick up Dr. Andersen and put her here on the table?

Sophie McNulty: Oh, the photo? 

Celia Ores: Yeah. 

Sophie McNulty: Yeah, let's go. Let's go find the photo.

Michelle Ores: I have it here, mom. 

Sophie McNulty: Michelle has them. 

Celia Ores: Oh, okay.

Michelle Ores: I have the two photos. I have the one of Dorothy. And the one of you in Switzerland in medical school.  

Katie Hafner: We’re back in the New York apartment of Celia Ores.

Dr. Ores is now in her nineties. She’s holding a black-and-white photograph of Dr. Andersen close to her chest, as she talks to Sophie McNulty, our associate producer. 

Celia Ores: When I came to the United States, she was the only one who treated me really, really well.

Katie Hafner: Dorothy Andersen took Celia Ores under her wing, passing on what she had learned about cystic fibrosis, and in turn, Dr. Ores dedicated a large part of her career to patients with the disease. 

Celia Ores: Every little bit of cystic fibrosis that I know is what she told me. She told me everything. 

If I had some issues with a patient that I don't fully understand, I went to her and told her that I don't know what I can do next for this patient.

Katie Hafner: But she couldn’t help everyone. In the 1960s, cystic fibrosis patients rarely lived past their mid-teens.

But the story of cystic fibrosis takes a turn for the better. 

And that’s the heart of this episode: we believe Celia Ores is the only living person who actually knew Dorothy Andersen well, and in holding that photograph, she’s holding Dr. Andersen’s legacy tight. In this episode, we want to tell you about that legacy—and the progress that grew from her life’s work.

Katie Hafner: When she was working in the 1940s and 50s, Dorothy Andersen was driven to get the word out about what she’d learned about cystic fibrosis. She went on lecture circuits, giving talks up and down the East Coast. When she was on vacation one summer in Europe -- or what she joked was a busman’s holiday—she agreed to speak at  medical schools and hospitals.

Unknown: Dr. Andersen?

Dorothy Andersen: If you place a child with the celiac syndrome on a diet designed for celiac disease, you will find that most children with any form of failure to thrive will improve in weight somewhat. 

Katie Hafner: It occurred to me while putting this season together that I didn’t have a clue what Dr. Andersen’s spoken voice sounded like. But I was lying in bed one night,  reading Scott Baird’s biography of Dr. Andersen, and I noticed that he mentioned this, just in passing:

“Her voice (from a professional recording in the late 1950s) was soft and musical.”

I wrote to Scott immediately, and asked if he had the recording. He sent back an excerpt from a recording in which Dorothy Andersen and a few other physicians discuss the syndrome known as “failure to thrive”. That’s a catch-all term that was used to describe children who weren’t growing or gaining weight as quickly as they should. 

Unknown: Dr. Andersen, we’d now like to hear what you have to say about the celiac syndrome, which includes cystic fibrosis and a variety of other conditions, some labeled as celiac disease. 

Dorothy Andersen: The three characteristics of the celiac triad are failure to thrive, the passage of large, undigested stools, and an enlarged abdomen. The two most common diseases in this group are cystic fibrosis of the pancreas and gluten-induced celiac disease. It’s fairly easy nowadays to sort out the cystic fibrosis cases from the rest by means of the sweat test. 

Katie Hafner: Hearing her voice was a revelation. It was like hearing about someone for months then finally meeting them.

But despite all the work Dr. Andersen had done, at the end of the day, CF was still deadly and the stories of the patients were incredibly sad—for the families, of course, but also for the doctors.

Celia Ores: Well, you go home and cried. It was very, very difficult for me to adjust to it. Because I would see young children that I tried to save from dying. And I didn't always succeed.

Katie Hafner: As a pediatrician in the 1960s, Celia Ores did all she could to extend the life of her patients. As did Dorothy Andersen.

Celia Ores: It was a function to maintain the patient as best you can, as long as you can.  And that's exactly what we were doing.

Doris Tulcin: I knew Dorothy Anderson because she diagnosed my daughter who has cystic fibrosis.

Katie Hafner: That’s Doris Tulcin. You met her in episode one. Mrs. Tulcin took her daughter Ann to see Dr. Andersen in 1953, and she helped start the Cystic Fibrosis Foundation in the 1950s. 

Doris Tulcin: And I know that if she were alive today, she would be amazed at the journey that we've gone on for over 65 years.

Katie Hafner: Sadly, Dorothy Andersen’s own health took a nosedive in the early 1960s.

Celia Ores: Every evening around four o'clock we would have some meeting. And there was five or six doctors, and some of the doctors she liked she would invite. So she would make some tea and we would talk about subjects such and such.

And one day she said in the evening, what are we going to talk about tonight? And the doctor, a male doctor, said, why don't we talk about Dorothy’s smoking? She said, “You know, I like you very much. I think you're a very good doctor and you're a very nice human being, but if you behave like this, I will ask you not to come to our meetings.”

[Sophie laughs]

Sophie McNulty: She was very tough?

Celia Ores: Well, she didn't want to leave the smoking.

Katie Hafner: Research was starting to show that smoking was deadly.

Audio Clip: The committee has reached the overall judgment that cigarette smoking is a health hazard of sufficient importance to the United States to warrant remedial action. 

Katie Hafner: But many people in the 1950s and 60s—even doctors, including Dorothy Andersen—were in denial. She was a lifelong chainsmoker. Almost everyone we spoke to about her mentioned it—and this was all the more surprising since she spent so much of her professional life examining lungs that had become incapable of exchanging air.

Smoking eventually killed her. 

Sophie McNulty: Do you remember the last time you saw her?

Celia Ores: Yes. Uh, she was in a room alone and there was a sign, no, no entry, but she called me and I went to her to see her. 

Katie Hafner: Dr. Andersen had always worked to protect Dr. Ores in an environment that was less than friendly to women. 

Celia Ores: And she said that she wanted to apologize to me that she didn't do more for me than she should have. 

I told her that I lived under Hitler, I lived under Stalin, and I think I'll be able to survive the people in this unit. If I don't get as much in money or fame, that doesn't bother me.

It was very difficult because the women were considered for nothing.

Katie Hafner: Dorothy Hansine Andersen died on March 3, 1963. The cause was lung cancer. She was buried in Chicago alongside her parents. 

Sophie McNulty: After she died, how did your work change?

Celia Ores: I felt lonely in the hospital. I continued to take care of the children just as much as I did before, but it was... I didn't have anyone to discuss with the things that I discussed with her.

She was my guide. I could come to her and say, you know, such and such, that such and such, you know, I just felt comfortable when she was there. 

Katie Hafner: After Dr. Andersen’s death, her farm in the Kittatinny mountains in New Jersey—the farm on which Dorothy Andersen built her cabin with her own hands, the farm where she invited colleagues and friends and put them to work chopping wood, and laying brick for the fireplace, the farm Celia Ores would visit with her children—she left that to close friends. Today, that land is a nature preserve. 

Dorothy Andersen left her personal papers to Bessie Coombs Haskell. 

Wait. Who? We couldn’t find much documentation of this friendship, except the brief mention of the bequest. But, according to people we called, Bessie was a friend of Dorothy Andersen—or “Andy” as she was known to Bessie. Bessie Coombs Haskell ran a camp in St. George, Maine, called the The Blueberry Cove Camp, and used to be a dancer in New York…but we couldn’t find much more than that. 

Just what was the what, where, when and how of their friendship? What made Bessie Coombs Haskell so important in Dorothy Andersen’s life that she left her papers to this person, and not, say, to one of her friends in New Jersey, or to Celia Ores, or to another colleague at Columbia? It just goes to show you (and us) that there are many things we will never know about Dorothy Andersen’s life. 

As far as we can tell, Bessie Coombs Haskell kept Dr. Andersen’s papers until she died. After that, it’s anybody’s guess. We contacted the library in the small town of St. George on the coast of Maine, as well as the local museum and historical society. They had nothing. We did find Bessie’s grandson, who told us he was pretty sure he threw the papers away after his grandmother died. 

At the end of the day, a legacy comes down to the stories people tell us, yes, but also to the things left behind. What gets kept and what gets thrown away. It’s haphazard. Boxes get tossed in the trash. This is nobody’s fault, but still, it’s profoundly disappointing.

It’s profoundly disappointing because it’s not like Dorothy Andersen died in a previous millennium, in which case the lack of archival material would be totally understandable. But in the scheme of things, she died relatively recently.

So, one of the lessons I take from our dive into the life of Dorothy Andersen is this: if you’re clearing out the basement or attic of a relative who’s died, open the boxes. Don’t throw out  your grandmother’s papers, because you just never know.

Coming up, the second part of this episode: Cystic fibrosis in the decades since Dorothy Andersen’s death. I’m Katie Hafner and this is Lost Women of Science. 

[AD BREAK]

Katie Hafner: I’m Katie Hafner, and this is Lost Women of Science: “The Pathologist in the Basement.”

Given all we’ve just said you might think the story ends with Dorothy Andersen’s death in 1963. But it doesn’t. Her work has pioneered almost a century of science and discovery. To this day, Dorothy Andersen’s foundational research in cystic fibrosis continues to be built on. In the years since she died, the prognosis for CF patients has just gotten better and better and better. 

Dr. William Skach is the outgoing chief scientific officer at the Cystic Fibrosis foundation. He’s been working on this disease for more than 30 years. 

Bill Skach: Well, in the 50s, the therapies were really incredibly simple and supportive.

It was recognized that the mucus in the lung was thick and couldn't be coughed out. So hydrating that mucus became one of the key goals. And, and patients used to sleep in mist tents because they thought that the breathing in the mist would then soften those secretions, which didn't really work very well. 

Another problem at that time was antimicrobials, antibiotics, for, for the infections because the people with CF frequently got lung infections and that's really what caused most of the damage to the lungs, which was progressive, and, and eventually led to lung failure.

Katie Hafner: Parents were the lynchpin of the CF community. In the 1950s, with Doris Tulcin and a handful of others leading the way, parents banded together to form the Cystic Fibrosis Foundation. Today, the CF Foundation has a fund totaling more than $4.5 billion, which is about the same as the endowment of NYU.

Bill Skach: And I will say that from its very beginning, it was really a collaborative effort with the community, with the scientists, with the physicians, to try to understand the disease better and to really work with the technology and the science at the time to take all of our understanding about the disease and turn it into therapies.

Katie Hafner: And it was during this period in the 50s, when Dr. Andersen was still at the forefront, that the focus was firmly on treating symptoms—making CF patients as comfortable and functional as possible. But, as Dr. Skach points out:

Bill Skach: With symptomatic therapy, you could only go so far. If you didn't really know what caused the disease, you couldn't really attack the basic root cause and reverse it. And so we got fairly good at treating the symptoms, but not good enough.

Katie Hafner: Children were still dying. The life expectancy had slowly been increasing over the years, but it was still devastatingly low. 

For instance, in the 1980s, cystic fibrosis patients still weren’t expected to live much past their teens. Here’s Brian O'Sullivan, the pediatric pulmonologist you’ve already met. He’s been working with CF patients for more than three decades. 

Brian O'Sullivan: And I do remember one family where the teenage girl was, was very sick, had been in the hospital for over two weeks, getting IV antibiotics, and and she had continued to deteriorate, um, and her parents knew she was dying and, and the parents actually came up to me and asked me to give their child permission to die, because they couldn't do it, but they knew she was hanging on just for them. 

And so they left the room, I held her hand and told her that she had done everything she could do. She'd put up a great fight, but that she wasn't getting better.

And, uh, shortly thereafter she died, um, and her parents thanked me. Um, and that kind of experience doesn't leave you.

Katie Hafner: Around this time, scientists began redoubling their efforts in basic research, much of it funded by the Cystic Fibrosis Foundation.

This takes us back to Francis Collins—the outgoing director of the NIH. Back in the late 1980’s, as a geneticist, he led a research team at the University of Michigan that was furiously searching for the CF gene, along with Lap-Chee Tsui, at the University of Toronto.

Francis Collins: Lap-Chee and I met at a genetics conference in 1987. And it was clear we were all really struggling, trying to find what was quite literally, in my view, a needle in the haystack and the haystack was really big and the needle was hard to find. And we sat in the sun and talked about what each of our labs was doing as far as our approaches and realized that our approaches were not the same. They were actually beautifully complementary and we kind of decided on the spot and much credit to Lap-Chee, that he was willing to take this leap as well, that we would just merge our labs and we would stop competing. And we would basically become one family of researchers between Toronto and Ann Arbor.

And what seemed like it might be an unsolvable problem got solved in just about two years.

Jane Grogan: Can you describe the moment when you and, and/or you and the team knew that you had the cystic fibrosis gene or the gene that causes cystic fibrosis?

Katie Hafner: That’s Jane Grogan, our scientist-in-residence.  She’s an immunologist by training and currently running research in cell and gene therapy at GraphiteBio in San Francisco.  

Francis Collins: At the time I remember, uh, we were at a meeting. He and I were at Yale. It was one of those human genetics meetings and, uh, he had set up a fax machine in his room. We were all staying in the dorms at Yale, which were, shall we say a little austere.

And we had a very long day. And at the end of the day, he and I went to his room where the fax machine was. And there was all this paper on the floor. That's the way we communicated back then, there was no email.

Jane Grogan: Some of us sending furious messages, right?

Francis Collins: Yes! ‘Cause it was that day's data. And so we pulled the papers up off the floor and we began to look at the evidence that this three base pair deletion in a previously unknown gene correlated with cystic fibrosis and that as we looked through the data, it got better and better.

And that was it. That was it for me. That was a rainy night in May, 1989, in New Haven. 

And I was like, over the moon, excited.

Katie Hafner: This discovery was a big big deal—it was on the cover of the journal Science, and it was all over the popular press too. Now that the gene abnormality had been identified, it seemed that a cure for CF was just around the corner. 

Katie Hafner: And the discovery of the gene has led to all kinds of things, right?

Bijal Trivedi: That's right, that’s right. But you know, it's interesting, when they discovered the gene in 1989, it was very early days and people were just learning about genes and genes that cause diseases. 

Katie Hafner: That’s Bijal Trivedi, the science journalist we interviewed in episode 1. Last year, she published Breath from Salt, the definitive and lengthy history of cystic fibrosis. 

Bijal Trivedi: They were trying this new type of therapy called gene therapy. So the understanding at the time was, if you discover a gene for a genetic disease, then you can give the healthy version of the gene to people who are sick, because they carry a mutation. You know, they tried that and it, it didn't work. In fact, it, it failed quite catastrophically.  

Katie Hafner: It turned out that the scientists couldn’t find a way to get the genes to take, often because they were delivered along with a harmless virus, which the body’s immune system attacked. 

Bijal Trivedi: Just finding a gene is not a guarantee of a cure.

And the disease was once again, deemed, you know, in the mid 90s, it was deemed incurable. Nobody could figure out how you would ever treat it because a broken piece of DNA—you couldn't just shove it into the patient and have it work like it should.

And you know, that was a really difficult time for, for the cystic fibrosis community because they invested all this time, all this research funding in finding a gene and then in gene therapy, trying to figure out, how do you get this healthy gene into the lungs of sick patients? And it just was not easy.

Katie Hafner: After the gene was found—it’s known as CFTR, short for cystic fibrosis transmembrane regulator—it ended up being about a decade until the next aha moment.

But, this next breakthrough was a big one. Scientists realized that there was not just a single mutation in the gene, but there could be thousands that lead to the defective protein found in CF patients. So the scientists shifted from studying gene therapy to looking at this single defective protein. 

By the 2010s, drugs were developed that actually helped correct this protein. In 2019, the FDA approved Trikafta, the latest version of these drugs. Trikafta is a combination of three so-called modulator drugs—drugs that help improve protein function. Here’s Francis Collins again.

Francis Collins: And here's where, over the course of now the last three or four years, we have arrived at an amazing place. Where Trikafta, this combination of drugs that does have this effect on the common mutation, this drug combination is almost miraculous in terms of what it does to reverse the problems.

And I have seen so many reports, uh, of large-scale studies, but I've also gotten incredible personal comments from CF patients who were, many of them, in really difficult places. And then within a few days of starting this drug would say, I can breathe again. This is different. I am, I'm a different person. I was about ready to say I better get on the lung transplant list.

Trikafta Patients Montage: “I could feel it working…..I’m literally, I think it was like 10 hours after I took my first dose ... .Sort of head open up, my nasal passages open up…. I started clearing out a bunch of mucus; it was just like coming out, so easily, moving out….My nose started running, like, it really started running. It’s an initial purge where like all this stuff came out of my lungs….And then the next day, again, I woke up, and it was like, ahhhhh, I can breathe even better now. It was crazy, like my energy was better….You know they would say, mom, you know, I don’t think I’ve ever been able to breathe this deeply before….You know, I could keep up with my toddler, without like, feeling like I was gonna fall over and faint….If, if this were before that drug, I would easily have coughed 150 times by now….I mean, the Trikafta made a huge difference….I felt like I hadn’t felt since I was a kid….It was just like this whole new...life.”

Bill Skach: And if people are started on those drugs in early lifetime. So in their, you know, early childhood, those individuals very likely will not die from CF. They will live a normal life span and have relatively normal lives.

Katie Hafner: However, one huge drawback with Trikafta is that it doesn’t work for everyone. 

Trikafta works on the most common CF mutations. But that means that the basic defect in about 10% of CF patients is still not being treated.

This leads us back to focusing on the gene. But today we have modern techniques to actually edit genes, with CRISPR—the genetic scissors.  Emmanuel Charpentier and Jennifer Doudna, yes, two female scientists, won the Nobel Prize in chemistry for their work on this in 2020. 

Perhaps this gene editing technique could help everybody with CF.

Francis Collins: The gene editors. This is really getting to the point of being like a word processor where you just say, find and replace.

Katie Hafner: Gene editing technology acts like a cursor placed next to a typo, capable of editing a gene at a level so granular it can change a single letter in a long genetic sequence.

Leonela Amoasii: I'm Leonela, um, and I'm a gene editor.

Katie Hafner: That’s Leonela Amoasii, a molecular biologist who specializes in gene editing. She spoke with Jane Grogan. 

Leonela Amoasii: And I'm really excited to be in that field because it feels like, um, my career path and my science kind of led me to this incredible opportunity to do something about those diseases and how we can correct them.

So what we looking into...that we’re really trying to understand how we can reassemble that code almost like a puzzle, if you think about it. How you can re-puzzle the, the code to make sure that we get the functional, uh, protein to really do its proper role in the tissue.

Jane Grogan: So, this may be a bad analogy, but I think of this a little bit like a sweater that's dropped a stitch and you have to go in and correct that hole or else the hole will get bigger. The sweater won't, you know, be a sweater anymore. Um, and you could go in with black thread, but then you get a hole that's just looking patched up.

Whereas if you go in with the exact material and the exact wool and precisely repair that, then you would never know that there'd been a defect.

Leonela Amoasii: Yeah, that's a great analogy. That's exactly what's allowing really, um, this technology to do. 

Katie Hafner: But the hard part is figuring out how to get the gene editing molecules to the right place in the body. We’re talking about editing a single gene—tens of thousands of which would fit into a period on a printed page. 

Francis Collins: It's all about delivery. The rest of it maybe seems straightforward, but delivery is not. And both you have to get it there and you have to evade the immune system's tendency to say, oh no, you don't. In which case you don't get the response for more than a brief time.

Maybe in the next 10 years, we would have the ability to effectively zip code, uh, your gene editor, or for that matter, a drug, uh, to the exact cells in the tissue where you want it to go, uh, safely and efficiently without necessarily having to go other places where there might be some side effects. But if you had this gene editing approach worked out, that could be scalable.

That's the sort of thing. If you knew how to do the delivery, you knew what the mutation was you needed to fix, then why couldn't you imagine a scenario where you apply that to thousands of diseases, that's the dream.

Katie Hafner: Speaking of dreams...

Jane Grogan: And I gather, back in 2009 at a cystic fibrosis conference in Minneapolis, uh, you were caught performing a song about cystic fibrosis on stage.

Francis Collins: That's true. A song I wrote about, uh, what we might hope for. Yeah. The title of the song is Dare to Dream, about all our brothers and sisters breathing free. And I got everybody to sing the chorus and uh, boy, it was hard not to lose it. That was such a powerful moment. All those people in that room, many of them who had spent decades working on the research, many of them, also family members of patients and some patients themselves, and all on their feet daring to dream.

Jane Grogan: Would you be willing to sing a line?

Francis Collins: [Chuckles, then sings] Dare to dream, dare to dream, all our brothers and sisters breathing free, unafraid, our hopes unswayed, till the story of CF is history...

Katie Hafner: Dorothy Andersen worked on something she never managed to cure. She seldom saw kids live past their teens. Yet she did live long enough to see things improve. If she saw how far things have come, I think she’d be astonished.

Think about all those young children who died on her watch. The fact that many people can now expect to live a normal life span is nothing short of a miracle. 

She couldn’t have dreamed that we would be ultimately editing genes with chemical scissors, or that two women would win the Nobel Prize for that discovery. But she must have known in her heart that progress was impossible without truly understanding the nature of this terrible disease. Because you can’t begin to attack a disease until you fully understand its underlying biology and she did that, starting with the first time she performed an autopsy on a three-year-old child, and had the suspicion that this was something very different from what prevailing wisdom had dictated was the cause of death.

Four years before her own death, she seemed to understand that her work had begun paving a way to a brighter future for these kids. This is something she captured with startling prescience in 1959, in a letter she wrote to the father of a CF patient in Australia. She wrote, quote: “It used to be true that children with this disease rarely lived past their fifth birthday. Now, however, with early diagnosis and better care, many are enjoying life at least to the later teen-age and early twenties. It is too soon to know how their future will be. We have come a long ways but still have far to go.” 

[music cue to transition]

Katie Hafner: Before we close out this season, I want to jump in and talk a little about what’s changed since we first aired this episode in 2021. 

Trikafta, which you heard about earlier, is the combination drug that works to fix the “broken” protein caused by CF. It has been nothing short of miraculous. 

Brian O'Sullivan: When I was a medical student and, first starting in the CF world, if we made the diagnosis of CF with a baby, we met the family with a box of tissue paper because we knew that this was going to be a sad diagnosis and we were going to have to tell them it was likely the child was going to die very young.

Katie Hafner: That’s Brian O'Sullivan, the pediatric pulmonologist we heard from earlier in the episode. We interviewed him again ahead of the re-run of this season. 

Brian O'Sullivan: Nowadays, when I make the diagnosis, I say, eh, you know, we’ve got medicines that change this and we expect a full healthy life span for your child. Trikafta has made an amazing difference for our patients. No question. 

Katie Hafner: Brian’s patients, for the most part, live normal lives–they play sports, they go camping, they participate in normal school activities, and they no longer spend weeks on end in the hospital. Brian even has a former patient who ran the Boston Marathon. 

Brian O'Sullivan: Years ago, that would have been impossible to imagine. 

Katie Hafner: The results have been so dramatic that CF patients don’t automatically qualify for the Make-A-Wish program anymore. And that’s a good thing to be disqualified for.

But, like any medication, Trikafta has brought with it unintended consequences. And more of these are coming to light now that the drug has been available for nearly five years.  Some of those consequences have been positive–women with CF  have found it easier (and maybe safer) to get pregnant. And, if the baby being carried also has the CF gene, that baby will  benefit from the Trikafta the mother is taking, as well…

Brian O'Sullivan: There’s a group of those babies, and it’s only a handful that have been documented so far, who are born with genetic CF, but don’t have clinical CF. Their sweat chlorides are normal. Their newborn screen is normal. Their pancreatic function is normal. Because they’ve spent their fetal life bathed in Trikafta, they don’t have the signs and symptoms of cystic fibrosis. 

Katie Hafner: Which is absolutely mind-blowing. 

But, there are a few drawbacks. Trikafta can damage the liver and it can cause cataracts. And perhaps more perplexing…

Sarah Zhang: The big question mark that’s really been the discussion within the CF community is the link to these neuropsychiatric side effects. 

Katie Hafner: That’s Sarah Zhang, a staff writer for The Atlantic who’s been writing about the dramatic ways Trikafta has changed the CF landscape.

Sarah Zhang: They aren’t proven. But there have just been lots and lots of anecdotal reports of patients starting Trikafta and then experiencing things like really intense insomnia or anxiety or depression of a really different kind than sort of, you know, what they had ever experienced before, like really dramatic. And then that going away as soon as they stop. 

Katie Hafner: While we hope to understand why this is happening, and how this relates to Trikafta in the future, for now it's something of an unknown for a small percentage of CF patients. 

And this is one of the many unknowns in the CF world. Another unknown how to handle all of the philosophical questions this new era of CF treatment raises. 

Sarah Zhang: What came along with this kind of beautiful and life changing miracle sometimes was this existential question of okay, what do I do with my life now? Maybe I didn’t plan to have a future. Maybe I never planned to have a career. Maybe I never planned to have a family. Maybe I spent all the money in my retirement account because I expected to not make it to retirement. 

Katie Hafner: In the course of  her reporting, Sarah looked for a historical parallel to what was happening in the cystic fibrosis community. And she found one. In the 1990s, when the first really effective drugs for HIV and AIDS came out, patients had to grapple with these same questions. What now? How do I live a life I didn’t plan for? 

Social workers called this phenomenon the Lazarus Syndrome. 

Sarah Zhang: Because you had people who kind of were resurrected from their dead beds, like Lazarus in the Bible.

Katie Hafner: Like with AIDS in the 1990s, this abrupt change in life expectancy has caused a sort of reckoning for some CF patients .

But, in some ways, getting to rethink your life now that you’ll have a lot more of it is, in itself,  a privilege. And one not afforded to all CF patients. Some have stopped taking Trikafta due to side effects. Others have had so much lung damage that they still require intensive care, even if they’re on Trikafta. And then there’s the price – Trikafta costs a shocking  300,000 dollars a year.

And finally, as we spoke about earlier in this episode, Trikafta doesn’t work for all CF mutations – only the most common one. So, for about 10% of CF patients, Trikafta isn’t really an option.

So, what’s next? What about all of those for whom Trikafta hasn’t been a life-changing miracle? 

Well, for starters, Vertex, the company that developed Trikafta, just published the results of a clinical trial for a new combination drug. 

Brian O'Sullivan: We all know taking medicine once a day is easier than taking medicine two or three times a day. 

Katie Hafner: That’s pediatric pulmonologist Brian O'Sullivan again. 

Brian O'Sullivan: Right now, Trikafta is a twice a day medication and the new product that Vertex is working on is a once a day medication. So, we do have the potential for a new CF medication coming out in the new future that may be even better than Trikafta, but certainly will be easier to administer. 

Katie Hafner: There’s hope that some of the patients who’ve stopped taking Trikafta due to the side effects may respond better to this new drug. 

And scientists are still looking into gene therapy– something that could benefit everyone.

Brian O'Sullivan: There are CF gene therapy trials going on right now. That’s still a little bit of a … I don’t want to call it a pipe dream, but a goal that’s out in the future. We’re not there yet. I don’t want to take a guess as to how long it will take, but I will take a little guess and maybe say five to ten years. It’s not in the immediate future, but people are working on that. 

Katie Hafner: So even though there’s more to do, we’ve really come such a long way.  

Brian O'Sullivan: I think Dorothy Andersen would be incredibly proud of what her discovery has led to…and to be able to see it become a treatable disease I’m sure was in her wildest dreams, but something she probably thought would never happen. And for her to be able to see this happen would be quite amazing. So maybe from on high, she is seeing this.

[Beat and music to transition…]

Katie Hafner: To end – just as we did in the original episode – I want to tell you the story of one particular CF patient. Because while the cystic fibrosis community is huge, it includes patients and doctors, research scientists and parents, drug makers] and a vast foundation,  the disease itself is felt acutely by individuals.

Brian McTear is a musician and producer who lives in Philadelphia.  He’s 51 years old and throughout his life, Brian has been chasing the CF life expectancy as he’s grown, the CF life expectancy has grown with him. So in essence, the course of his life has paralleled many of the advancements in treatments and drug therapies.

Brian has been on Trikafta since 2019 and the drug has massively improved his life, especially his ability to sing his way through a song without stopping over and over again to cough. 

But for Brian, it’s important to keep hope alive but also to know that the work isn’t done. For the end of this season, we wanted to give a CF patient the last word with a song. After we talked to Brian, we asked him to write a song in Dorothy Anderson’s memory.

And here’s what he composed. The title of the song is “Breakfast in the Snow”, and Brian sings it with full, clear, strong lungs.  

Brian McTear: [sings] The line of succession is a noble tree. It isn’t a profession, it’s more like the air we breathe. The hero learns … 

Katie Hafner: And that’s our story—”The Pathologist in the Basement.”

Brian McTear: [sings] And the future, it’s goes where she can’t go. Tell them that Breakfast in the Snow.  

Katie Hafner: This episode of Lost Women of Science was produced by Tracy Wahl and Sophie McNulty. Abdullah Rufus and Hansdale Hsu were our sound engineers, Lizzy Younan composed the music, and Nora Mathison and Lexi Atya did the fact checking. 

Thanks to Jeff DelViscio and our publishing partner, Scientific American. Thanks also to my co-executive producer Amy Scharf and to senior managing producer Deborah Unger.

Lost Women of Science is funded in part by the Alfred P. Sloan Foundation and the Anne Wojcicki Foundation. We're distributed by PRX.

Thanks for listening, and for more, go to lostwomenofscience.org and subscribe, so you'll never miss an episode. I’m Katie Hafner. See you next time. 

Brian McTear: [sings] And the river flows where none of us will go. Ooh uh uh oh, OK, Breakfast in the snow.