The Question Mark

BRIAN O’SULLIVAN: Cystic fibrosis back then…

BIJAL TRIVEDI: ...was just considered a death sentence.

SARA KOMINSKY: It feels like you’re suffocating to death.

BIJAL TRIVEDI: Dorothy Andersen…

SCOTT BAIRD: She was the first to diagnose CF in a living patient...

BIJAL TRIVEDI: She was down in the basement doing these autopsies.

SCOTT BAIRD: And the first to recognize that CF was a hereditary disease...

BRIAN O’SULLIVAN: I mean, she’s just brilliant. And she put this puzzle together.

SCOTT BAIRD: Dorothy Andersen was able to push the boundaries.

CELIA ORES: She was kind, intelligent, and very bossy.

KATIE HAFNER: Welcome to Lost Women of Science. I'm Katie Hafner. What you just heard was from the intro to our very first season, “The Pathologist in the Basement.” We're returning to it now, almost three years later for a few reasons. First, the month of May is cystic fibrosis awareness Month and it's the birthday month of Doctor Dorothy Andersen who was born on May15th, 1901. She's the pathologist who first identified cystic fibrosis in 1938. And she was the subject of that very first season.

Everyone at Lost Women of Science fell in love with this story while we were making it three years ago. And there are a lot more of you listening to us now. So we want to cue more of you in on the amazing woman, Doctor Andersen was, she was flat out brilliant. A total outside of the box thinker.

She was intrepid in her life and in her work and she was kind and generous when it came to giving credit to her colleagues, maybe too generous. However, when we started working on the season, Dorothy Andersen was well, pretty much lost to history. But that's no longer the cas. Since the “Pathologist in the Basement” first came out, there have been some notable changes both in the way Dorothy Andersen has been recognized and in CF treatment, in general. An example is in November, 2021, when Scott Baird, a pediatric critical care doctor at Columbia University, Doctor Andersen's own institution, published an exhaustive biography on her. His reason for digging up her story at the time was similar to ours. She didn't get the credit she deserved during her lifetime.

And then in 2023 the Cystic Fibrosis Foundation renamed its highest scientific honor.

It was originally named after Paul de Sant Agnesi, who was one of Doctor Andersen's mentees. And now it's named for them both. Some progress there.

And very recently with support from the Craig Newmark philanthropies, we've been busy updating Dorothy Andersen's Wikipedia page, which was not great. So, Dorothy Hansine Andersen is still not a household name, but slowly and very surely she's getting some of the recognition she deserves.

As for the science we're now approaching five years since the FDA approved Trikafta, a life changing drug for many CF patients.

BRIAN O’SULLIVAN: Trikafta has made an amazing difference for our patients. No question. 

It’s a drug that works for about 90% of all CF patients – and turns what once was a death sentence into a disease that can be pretty manageable. 

SARAH ZHANG: What came along with this kind of beautiful and life-changing miracle sometimes was the existential question of okay, what do I do with my life now? 

KATIE HAFNER: In episode four, we'll catch up on where we are now and explore what “life changing” really means.

But for now, let's return to where Lost Women of Science first began: episode one of “The Pathologist in the Basement,” which originally aired in November 2021.

KATIE HAFNER: We're calling this first season “The Pathologist in the Basement.” And we'll be shining a light on Dr. Dorothy Andersen. She was a physician and pathologist whose brilliant and dogged detective work in the 1930s led her to solve a medical mystery. And that mystery was this: What was the real nature of cystic fibrosis, a devastating illness that was killing young children and had been routinely misdiagnosed, for years and years?

FRANCIS COLLINS: So, I’m Francis Collins. I’m a physician and a scientist and currently the director of the National Institutes of Health.

KATIE HAFNER: In addition to leading the NIH, Dr. Collins in the 1990s led the Human Genome Project, the massive effort that unraveled the mysteries of DNA. Dr. Collins knows a little about Dorothy Andersen.

FRANCIS COLLINS: I know her as the person who, in 1938, described this disorder, cystic fibrosis of the pancreas.

KATIE HAFNER: But he was a bit chagrined to admit, that’s pretty much all he knows.

FRANCIS COLLINS: I don’t know much about her career, her person, as somebody who must have traveled an interesting journey as a woman working in medical research.

KATIE HAFNER: As one of the scientists who isolated the cystic fibrosis gene in 1989, Dr. Collins stood on the shoulders of path-breaking scientists like Dr. Dorothy Andersen. He is also an outspoken champion of women in science. So if he doesn’t know much about her, who does? 

In this episode, we’re going to tackle two mysteries. The first is the disease itself–cystic fibrosis. In the 1930s, it was a cruel killer of infants that was routinely misdiagnosed—until Dorothy Andersen solved the puzzle. And then we’ll turn to the mystery of Dorothy Andersen herself, an ingenious medical sleuth who left behind very few clues for those of us trying to understand what made her tick. 

Dorothy Andersen stood out. She was one of the very few women working as a physician in the first half of the twentieth century.

BIJAL TRIVEDI: In the thirties, women made up only five percent of practicing physicians, so she was a rarity.

KATIE HAFNER: That’s Bijal Trivedi, a science journalist whose book, “Breath from Salt,” describes the history of cystic fibrosis. 

BIJAL TRIVEDI: Dorothy Andersen had always wanted to practice medicine. She was a determined woman and she wanted to have a career, and settled for becoming a pathologist.

KATIE HAFNER:  At the time, there were few options for women with medical degrees–many hospitals wouldn’t hire women, and even if they did, women usually got pigeonholed to specialties like gynecology or psychiatry. In those days, men and women alike often objected to being seen by female physicians, which also led many women to  pathology, where doctors rarely interacted with patients.

Pathologists study the nature and cause of disease. And in the 1930’s, one of the only ways to investigate how disease ravaged the body was through autopsies. 

That’s how it came to pass one day in 1935 that Dr. Dorothy Andersen stood at  a stainless steel table in the basement of Columbia’s Babies Hospital in Washington Heights. Her task was indescribably tragic, but she was all business as she set upon it—to dissect the organs of yet another child who had died.  This child was a 3-year-old girl.

The girl had come into the hospital a year before...

BIJAL TRIVEDI: ...and she looked terrible. She had a distended belly, skinny limbs, foul, persistent diarrhea, and she had been diagnosed with celiac disease and sent home. But there she was a year later, and she was dead. And so Dorothy Andersen started doing this autopsy and slowly began to realize that this was not celiac disease.

KATIE HAFNER: At the time, it was common for children with cystic fibrosis to be misdiagnosed with celiac disease–

A lot of people are sensitive to gluten, and a subset of those people have full-blown celiac disease—an immune reaction to wheat and rye that inflames the intestine and can cause severe GI symptoms. This inflammation is also a symptom of cystic fibrosis. Of course these are two very different diseases with very different treatments and outcomes. But, at the time, the misdiagnosis was understandable. And there were two reasons for it.  First, they had the GI symptoms in common. That was number one. And number two: Frequent pneumonias and breathing problems were misattributed to the malnutrition that accompanies celiac disease instead of a problem with the lungs. 

So as Dorothy Andersen began examining the organs of the 3-year-old child...

BIJAL TRIVEDI: ...she realized that there were a lot of differences, and the most profound differences were in the lungs. And as she started to look into the airways of the lungs, she saw that they were, they were plugged full of mucus, thick, sticky, green mucus. But when she cut into the pancreas, I mean, she could barely get the scalpel in. And when she sort of tried to cut, she heard a scraping sound, as if she were cutting through grit or sand. All she could see was this, this fibrous, tough material, completely enveloping the whole gland. So, you know, she knew that this was something very, very different. 

WILLIAM SKACH:  You know, with Dorothy Andersen's description of the actual entity of CF, it became clear that it was multi-system. 

KATIE HAFNER That’s Dr. William Skach, the outgoing Chief Scientific Officer of the Cystic Fibrosis Foundation.

WILLIAM SKACH: It did not just affect the lungs or the pancreas, but affected multiple tissues.

KATIE HAFNER: To understand just how cystic fibrosis affects multiple systems, we need to take a brief medical excursion into the body–and specifically, its tubes. Bear with me. One of the miracles of our construction is that we’re filled with tubes–conduits that move stuff from one place to another. Perhaps the most familiar ones are blood vessels–an intricate arborized network of miles of tubes that circulate blood. Block these tubes–most commonly by a clot–and the tissue at the far end dies. When it’s the brain, it’s a stroke. When it’s the heart itself, it’s a heart attack.

The lungs also have blood vessels, but the most important tubes in and out of the lungs are the ones that allow for oxygen to come in and carbon dioxide to come out. If those tubes are blocked, we can’t live. 

The pancreas also has tubes–the main one being the pancreatic duct. The miracle here is that the pancreas, which is producing digestive enzymes capable of breaking down a piece of steak in our intestine, doesn’t digest itself. The reason is that the corrosive enzymes flow into these tubes, and from there they enter the intestines. But block these tubes and the juices back up into the pancreas itself, to devastating effect. 

What Dorothy Andersen discovered was that the primary problem with these patients was very different from what causes celiac disease. 

And so Dorothy Andersen’s discovery was that the lungs and pancreas shared the same fatal problem—that the real issue wasn’t inflammation in the wall of the intestine. It was the clogging of the tubes in the pancreas and the lungs. Something was gumming up the tubes like molasses in a straw.

Again, Bijal Trivedi.

BIJAL TRIVEDI: With this disease, patients get persistent lung infections that destroy lung tissue and limit the ability to breathe. This thick mucus also builds up in their airways, so they can’t actually inhale properly. They can’t take a full breath and breathe deeply. They can’t laugh properly, because they don’t have the air to laugh.

SARA KOMINSKY: It feels like you’re suffocating to death. And at the point before my first lung transplant, I couldn’t even walk across the room, even on oxygen, without gasping and feeling like I’d…throw up because it took so much effort.

KATIE HAFNER: That was Sara Kominsky who’s 50 now, describing what it’s like to have cystic fibrosis. Next is Mallory Woodruff, who’s in her mid-30s.

MALLORY WOODRUFF: I started getting winded a lot easier. I started producing more mucus, cough, coughing up plugs. The plugs started getting, you know, thicker and greener, yuckier. And then, by the time I was in college...it was really hard to get to class, honestly. 

SARA KOMINSKY: All the other CF patients I met during my childhood and young adulthood, by the time I was in my mid-20s early-30s, all of them had passed away.

KATIE HAFNER: In the 1970s and 80s, when Sara and Mallory were born, CF patients rarely lived past their teens. 

But the prospects are improving. Today, the life expectancy for CF patients is around 50. And a breakthrough drug called Trikafta was approved by the FDA just two years ago. It’s very expensive, but Trikafta promises to dramatically improve this prognosis and the patients’ quality of life.

Dorothy Andersen wasn’t setting out to identify an entirely different disease. But she kept an open mind, open enough to process surprising findings and consider the possibility that the medical community’s prior understanding was just plain wrong.

BRIAN O’SULLIVAN: Well, I have Dorothy Andersen’s papers right here by my desk. In fact, I keep them in a bag that I bring back and forth to work, pretty much all the time.

KATIE HAFNER: That’s Brian O’Sullivan, a pediatric pulmonologist who teaches at the Geisel School of Medicine at Dartmouth. 

BRIAN O’SULLIVAN: And the first is one from the American Journal of Diseases of Childhood in 1938. And it’s title is “Cystic Fibrosis of the Pancreas and Its Relation to Celiac Disease: A Clinical and Pathological Study,” by Dorothy H. Andersen, MD, New York.

KATIE HAFNER:I first came across Dr. O’Sullivan’s name when he was quoted in a 2014 article in The Lancet, one of the most popular medical journals. The article was a brief biographical sketch of Dr. Andersen. And it turns out that every year when Brian O’Sullivan lectures to first-year med students about cystic fibrosis...

BRIAN O’SULLIVAN: The disease has obviously been around for millennia. It’s a genetic disease. 

KATIE HAFNER:  He  makes a point of paying tribute to this key figure in the history of the disease.

BRIAN O’SULLIVAN: I want to take a minute to call out Dorothy Andersen. This is a woman who, you know, in the 1920’s, late twenties, early thirties when she was going to medical school, there weren’t a lot of women in medical school. And it’s funny, I’m looking out at the audience now, and it’s almost all women. But it was very different in the thirties.

KATIE HAFNER: That 1938 paper he carries with him at all times was 50-pages long and written by a single author, which would be unheard of in today’s world of publishing, where there are usually at least half a dozen, and sometimes hundreds of authors on a paper. 

BRIAN O’SULLIVAN: There’s the old saying, “Luck favors the prepared mind.” The luck was that she was in a position where she saw some children, unfortunately, who had died of this problem. The prepared mind is Dorothy. I mean, she’s just brilliant, and she put this puzzle together. And so she recognized that she was seeing a group of children who had some of the hallmarks of celiac disease but on autopsy had very different problems.

KATIE HAFNER: That 50-page paper she published reviewed 20 cases from Dr. Andersen’s own institution and many more from other places, in an era where there was no Google Scholar. 

BRIAN O’SULLIVAN: She must have spent hours in the library finding these articles and then writing to other physicians and seeing if she could get their slides from autopsies to be able to compare to what she was seeing. 

KATIE HAFNER: She reviewed hundreds of pathology slides from other children believed to have died from celiac disease, until...

BRIAN O’SULLIVAN: She really spelled out that she was identifying a completely different disease, and it was the first time it really was recognized as a separate entity.

KATIE HAFNER: And she didn’t stop there. After recognizing cystic fibrosis as something different, Dorothy Andersen went back to work, trying to understand as much as she could about the disease. And she started racking up a lot of firsts. 

SCOTT BAIRD: She was the first to diagnose CF in a living patient, the first to emphasize diet and pancreatic enzyme replacement therapy in CF, the first to successfully treat pulmonary infection in CF with antibiotics, and the first to recognize that CF was a hereditary disease expressed in the manner of a recessive trait.

KATIE HAFNER: Scott Baird is a pediatric critical care doctor at Columbia University Medical Center and he’s seen scores of CF patients throughout his clinical career. Like Dorothy Andersen before him, Dr. Baird has spent the bulk of his professional life at Columbia, so there’s a kinship there. And Scott Baird, it turns out, isn’t just a fan of Dr. Andersen’s work; he’s on a quest to fill in the details of her life. 

SCOTT BAIRD: Dorothy Andersen, who never was specifically trained in pathology, never specifically trained in pediatrics, became a world-class pathologist, a world-class pediatrician, and clearly was a world-class researcher, somebody who was able to define and determine what might be associated with disease in patients, and who was able to push the boundaries. 

KATIE HAFNER: Coming up, we’ll start to untangle more about this mysterious scientist. I’m Katie Hafner and this is Lost Women of Science.

(AD) 

KATIE HAFNER: So now that we appreciate what Dorothy Andersen did, let’s try to unravel another mystery. Who she was. 

Dorothy Hansine Andersen graduated from Johns Hopkins Medical School in 1926, one of only 5 women in her class. But Hopkins was well ahead of its time. When the medical school opened in 1893, there were three women admitted to the first class. Harvard Medical School wouldn’t officially admit its first women until 1945!

Here’s Brian O’Sullivan again: 

BRIAN O’SULLIVAN:. Um, following that she went to Rochester and did an internship and then she wanted to become a surgeon. In that day, women just were not accepted as surgeons. 

KATIE HAFNER: In 1926, when Dorothy Andersen graduated medical school, there were practically no female surgeons. In fact, until 1975, the American College of Surgeons admitted five or fewer women a year. So Dorothy Andersen settled for a career in pathology.

In the medical community, pathologists sometimes have a reputation for not being people people, of working with dead bodies and lifeless organs for a reason. Pathologists seldom see living patients, except to do certain biopsies. But Dorothy Andersen was a different kind of pathologist. Here’s Scott Baird again: 

SCOTT BAIRD: She felt the suffering of others, and she did her best to try to minimize that whenever possible. It’s difficult to advance the care and advance medical knowledge at the same time that you're providing the sympathetic care she provided for all of them.

KATIE HAFNER: In the 1940s, cystic fibrosis was so new that parents had trouble finding physicians who knew much about it, or who were even willing to take on a new cystic fibrosis patient, especially when the prognosis was so grim and death so swift. At the time, it was rare for patients with CF to live past five. But word started to spread that there was this doctor in New York City who knew all about the disease. Desperate parents began bringing their kids to Dr. Andersen from all over the place. Here’s Doris Tulcin, whose daughter was diagnosed with cystic fibrosis in 1953.

DORIS TULCIN: And after taking her to many, many different doctors who could not figure out what was wrong, we went through an agonizing three months until a very dear friend of my mother’s, who was a nurse, read in a nurse’s magazine about a Dorothy Andersen and cystic fibrosis.

KATIE HAFNER: So Doris Tulcin took her daughter to see Dr. Andersen.

DORIS TULCIN: She was a dowdy-looking thing, with a bun in the back of her head, no makeup. She had on a lab coat. You could tell she was a big smoker because she smelled of cigarettes, but she was very kind. And you knew that she really, really cared about what she was doing for these kids.

KATIE HAFNER: Okay, so let’s see: Dowdy (by the way, I can’t think of a single time I heard a man described as “dowdy”), brilliant, a heavy smoker, great with a microscope, but what else?

We knew she’d grown up in North Carolina and Vermont and she’d been orphaned as a teen. She never married and dedicated her life to her work. And that piece in The Lancet that I mentioned earlier, it said this.  She described herself as a “rugged individualist.”

And I knew she earned her bachelor's degree in Chemistry and Zoology at Mount Holyoke College, a women’s college in South Hadley, Massachusetts. 

LESLIE FIELDS: My name is Leslie Fields, and I am the head of archives and special collections at Mt. Holyoke College.

KATIE HAFNER: The school keeps biographical files on many of its graduates, organized by graduating year. Dorothy Andersen entered Mt. Holyoke in 1918, the year the Spanish flu pandemic hit the country, and she graduated in 1922, not even two years after women got the right to vote. 

LESLIE FIELDS: So some students and alums might simply have a single biographical sheet that has a little bit of factual information about them. And others might have 50 boxes of correspondence. So hers is on the smaller side. So it is two thick folders. That’s the extent of what we have in her biographical material. They’re primarily made up of professional documents and administrative records from the college perspective on her. So we actually, we don’t have her personal papers here.

KATIE HAFNER: The alumni questionnaires that asked about marriage and children were left blank.  

LESLIE FIELDS: But her education section about graduate school and becoming a doctor, that’s in great detail. And there’s even a question about publications, and she usually writes something like, “Over 80 publications, too numerous to list here.”

KATIE HAFNER: That part makes sense. In terms of career accomplishments, Dorothy Andersen fulfilled the Mt. Holyoke promise. The school was a bastion of science education from the day in 1837 when Mary Lyon, a devoutly religious educator and self-taught chemistry professor, opened its doors. And much was expected of Mt. Holyoke’s students. 

LESLIE FIELDS: There is an expectation by Mary Woolley...  

KATIE HAFNER: Who was the president when Dorothy Andersen was a student. 

LESLIE FIELDS: ...that they are going to do something with their lives, they’re going to serve the world in some way. Helping others in some way was a real focus of the college community at that time. And then they’re sort of launched into the world, and I think for some of them, it looks like that was hard because maybe the world wasn’t quite ready to accept them as professional women in some ways. So out there, real options might have been more limited.

KATIE HAFNER: I couldn’t go to Mt. Holyoke in person because of COVID. So as I’m perusing the 80-page PDF that Leslie Fields’s colleague has sent, something catches my eye. It’s a questionnaire Dorothy Andersen filled out in 1944. There in the middle of the back page is this question: “Name and address of person most likely always to know your whereabouts.” Dorothy Andersen put a question mark.  Here’s this woman, 43 years into her life, and when asked, “Who will always know where you are?” she didn’t have an answer.

And it gets me to wondering, What does it mean to live a life filled with accomplishments and not to be able to answer that basic question? Who is going to preserve the memory of what you’ve done and who you were? I think this is how large pieces of a life go missing. They slip through the cracks of history and they’re lost. It means that big swaths of your life may be punctuated with a question mark.

Most of Dorothy Andersen’s colleagues have died, but there is one….

CELIA ORES: Can you put this down and we'd go and pick up doctor Andersen and put her here on the table?

SOPHIE MCNULTY: Oh, the photo? Yeah. Yeah, let's go. Let's go find the photo.

KATIE HAFNER:The people you will be hearing are Sophie McNulty, who’s our associate producer, Michelle Ores, and her mother—

CELIA ORES: My name is Celia Ores. I was born in Poland in the town of Dubienka, and we were forced to leave our homes when Hitler came to our home.

KATIE HAFNER: Dr. Ores eventually made her way to the United States and went on to be a prominent pediatrician herself. She’s in her nineties now, and she worked with Dorothy Andersen at Babies Hospital in the early 1960s.

Celia Ores completely revered Dr. Andersen. And it turns out that she even keeps a framed photograph of Dr. Andersen on a shelf, right next to her bed.

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.  

CELIA ORES: It’s um, this is in the country, she was.

SOPHIE MCNULTY: This photograph?

CELIA ORES: She had a country home and students were invited for groups. It’s a huge forest and it was family.

KATIE HAFNER: The black and white photograph was taken in the early 1960’s, just a year or so before Dr. Andersen died. She looks tough, as many people say she was, but also kind. The photo stayed on the table during the interview with Dr. Ores. And once in a while, while she was talking, she would glance over at it.

CELIA ORES: She was my supporter there. No man could come to me while she was alive and there and tell me any negative thing because they would be killed by her. So she was my protector and my guide, and she gave me the courage to do a lot of things. 

KATIE HAFNER: Dr. Ores stopped practicing medicine more than a decade ago, and her daughter Michelle has her mother’s papers stored in her basement in Connecticut.

MICHELLE ORES: We’re going down to the basement, where my mother kept her medical files.

KATIE HAFNER: At first, it looks like we’ve hit a dead end.

SOPHIE MCNULTY: It looks like most of these boxes are just from her private practice and continuing work at Columbia.

KATIE HAFNER: That’s Sophie again, she’s gone to Connecticut to look through Dr. Ores’s boxes. 

SOPHIE MCNULTY: I’ll let you know if I find anything.

KATIE HAFNER: Then, a discovery…

SOPHIE MCNULTY: Okay, I think I hit the jackpot. I just found two folders titled “Dorothy Andersen.”

KATIE HAFNER: In our next episode of Lost Women of Science we’ll dig through the boxes and see what we can find.

This episode of Lost Women of Science was produced by Tracy Wahl and Sophie McNulty. Abdullah Rufus andHansdale 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 Ann Wojcicki Foundation. We're distributed by PRX.

Thanks for listening, and for more go to LostWomenofScience. org so you'll never miss an episode.

I’m Katie Hafner, see you next time.