This Podcast Will Kill You - Special Episode: Lawrence Ingrassia & A Fatal Inheritance

Episode Date: March 17, 2026

For centuries, physicians noticed that cancer sometimes ran in families, but until the 1960s, an answer to this mystery remained out of reach. Only then were scientists beginning to unlock the cellular dynamics underlying cancer, and what they found finally allowed grief-stricken families to put a name and explanation to their experience. It wasn’t simply bad luck. It was genetics: a heritable mutation in a key tumor suppressor gene that greatly increases the risk of developing cancer in your lifetime, a condition known as Li-Fraumeni Syndrome. Journalist Lawrence Ingrassia belongs to one of those families; he has lost his mother, three siblings, and a nephew to cancer. In this TPWKY book club episode, Ingrassia joins me to discuss his book A Fatal Inheritance: How a Family Misfortune Revealed a Deadly Medical Mystery, where he weaves together his family’s story with that of the scientists who sought to uncover the cellular drivers of cancer. Tune in for a heartbreaking and inspiring journey. Support this podcast by shopping our latest sponsor deals and promotions at this link: https://bit.ly/3WwtIAuSee omnystudio.com/listener for privacy information.

This is exactly right. Hey, it's Alec Baldwin. This season on my podcast, Here's the Thing. I talked to composer Mark Shaman. It's about the hang. It's the pleasure of hanging out with the people that you're with.

You know, Rob and I was always a great hang. And journalist Chris Whipple. Every White House staffer, they work in a bubble called the West Wing, and it's exponentially more so in the Trump White House. Listen to the new season of Here's the Thing on the Eye Heart. radio app, or wherever you get your podcasts.

Hi listeners, I'm Annesonfield, the host of The Girlfriend Spotlight, and I've got some great interviews coming your way. I'm also excited to tell you that you can now get access to all episodes of season one, two, three, and four of The Girlfriends, and every single episode of The Girlfriend Spotlight, 100% ad-free, and one week early through the I-Heart True Crime Plus subscription. exclusively on Apple Podcasts. Plus, you'll get access to other chart-topping true crime shows you love, like betrayal, paper ghosts, Pikeson Massacre, The Brothers Ortiz,

what happened in Nashville, hell and gone, the godmother, and more. So don't wait, head to Apple Podcasts, search for iHeart True Crime Plus, and subscribe today. Hi, I'm Danielle Robe, host of Bookmarked, the podcast by Reese's Book Club. And this week, we are talking about a mom. Or maybe the woman who refused to be one. I'm sitting down with Maggie Gyllenhaal to unpack her new film, The Bride. And trust me, this isn't your grandmother's bride of Frankenstein. What I was more interested in was the monstrousness inside of each of us.

You can spend your life running from those things, or you can turn around and shake hands with them. Listen to Bookmarked, the Reese's Book Club podcast on the IHeart Radio app, Apple Podcasts, or wherever you get your podcast. When you feel uncomfortable, what do you put on? Biggie. You put on Biggie when you feel uncomfortable? Because I want to get confident. This is DJ Hester Prynne's Music is Therapy. A new podcast from me, a DJ and licensed therapist.

12 months, 12 areas of your life. Money, love, career, confidence. This isn't just a podcast. It's unconventional therapy for your entire year. Listen to DJ Hester Prins, Music is Therapy, on the IHeart Radio app, Apple Podcasts, or wherever you can. get your podcasts. Welcome to Dirty Rush, the truth about sorority life, the good, the bad, and the

sisterhood. With your host, me, Gia Judice, Daisy Kent, and Jennifer Fessler. The reality of Greek life has been a mystery for those outside the sorority circles until now. Is it really a supportive sisterhood that's simply misunderstood? Or is there something more scandalous having on campuses across the country? Let's get dirty. Listen to Dirty Rush on the Iheart radio app, Apple Podcasts, or wherever you get your podcast. Hi, I'm Erin Welsh, and this is, this podcast will kill you. You're listening to the latest episode in our TPWKY Book Club series, where I bring on authors of popular science and medicine books to chat about their work, the stories they cover, and the inspiration behind them. We have featured some wonderful books so far this series, and if you'd like to check out the full list of book club books, you're in luck.

Head on over to our website, this podcast will kill you.com, find the extras tab, and then click on Bookshop. That will take you to our Bookshop.org affiliate page, which has a bunch of podcast-related lists, including a book club list that has all the books from this season and past seasons. And if you have any book suggestions, episode topic suggestions, or just other thoughts you'd like to share with us, please reach out using the contact us form on our website. Two last things before moving on to this week's book, and that is to first, please rate, review, and subscribe if you haven't already. It does help us out. And secondly, you can now find full video versions of most of our newest episodes on YouTube. Make sure you're subscribed to Exactly Right Media's YouTube channel so you never miss a new

episode drop. Stories of scientific progress and discovery often portray scientists armed with facts and data, triumphing over death and disease. It's a forward march with a clear narrative arc, from a place of ignorance to one of enlightenment. And as much as we love tidy stories like these, science rarely happens that way. More often than not, it's a battle with each hard one inch of progress contested and dismissed before it's accepted. or it's a promising hypothesis that turns into a wild goose chase after years of time and resources have been spent. Maybe it's simply making slow, incremental headway on a puzzle. This zigzag two steps forward, one step back nature of scientific progress rarely makes it into the polished final product.

Nor does the human cost. Those whose lives ended prematurely because science didn't yet hold the answers, and their grieving families who were left to more. this painful loss. But these crucial elements are a feature of this week's book, A Fatal Inheritance, how a Family Misfortune revealed a deadly medical mystery by author Lawrence and Grascia. Part memoir and part medical thriller, a fatal inheritance takes readers through the riveting story of how two doctors, Dr. Frederick Lee and Dr. Joseph Framani, uncovered a key piece of the cancer puzzle, the P53 gene, when a family suffered heartbreaking loss after heartbreaking loss to cancer.

For Ingrossia, this is a deeply personal story, as his own family has been tremendously impacted by cancer, losing his mother, two sisters, his brother, and a nephew to different forms of this disease. When faced with such devastating loss, it's natural to ask, why me, why our family? But what if the answer brings you knowledge without a way to use it? In a fatal inheritance, Ingrossia grapples with this question, and by doing so, illustrates that knowledge can be both a blessing and a curse. But with continued support for scientific research, we can turn that knowledge into interventions that save lives and prevent heartbreak.

Through his meticulous research and compassionate writing, Ingracia leaves readers with a deeper appreciation of the human experience of cancer research and how vital it is to not give up hope. I'm very excited to share this conversation with you all, so let's take a quick break and get into it. Larry, thank you so much for joining me today. It's my pleasure, Erin. Your book, A Fatal Inheritance, it strikes this really beautiful and delicate balance between medical mystery and memoir, with these two stories ultimately converging as that mystery is unraveled. And not only do you showcase this truly transformative period in cancer research, but you also place it in a human context by discussing your family. What initially set you on the journey to write this

book? You know, my brother died a few years ago. And when he died, he was the last surviving member of my family. And my mother had died of cancer, breast cancer, when she was 42. I had two younger sisters die of cancer. One had an abdominal cancer. She died at 24. The other had lung cancer died at 32. And my brother had a son who had his first cancer when he was just two years old. And he died of his third cancer at age 39 after a desperate attempt to save his life by imputating his leg and hip. So I just wanted to know more about this rare genetic condition that had wiped out my family. I knew very little about it. It's called Lee from any syndrome. And all I knew at the time my brother died was that it was caused by a mutation in a

gene that normally prevents cancer from occurring. And that was kind of it. And so I just began this journey. I googled and what I saw initially just piqued my interest. And that's how it began, not with a plan initially to write a book. In fact, I say this was not a book that I ever intended to write, but once I began, I knew I was meant to write. When you knew that this is a book, this is becoming a book, did the shape of that book or the outline sort of change shape as you put it together, or did you have this vision sort of all along? Once I finally decided, it took some months of research before I said, yeah, I think this is a book. I had in my mind's eye how this would intertwine, that it would be a story about my

family and families like mine who had really been devastated by this hereditary cancer condition, along with the story of the researchers, dedicated researchers, who spent years, decades before they solved the mystery. And that actually was part of the thing that intrigued me about the book and the whole condition. It's just how long it took to figure this out. But initially it began actually, you know, kind of with this search and finding out that this was a rare condition, it was very prodigious. Families that had it, there were a lot of cancers at young ages, all different kinds of cancers, too, which is a little bit different from a lot of cancer conditions. And I saw that one of the two researchers who this is named after and who led the effort to solve this medical mystery, Joseph Brownini Jr. was still alive.

he was in his late 80s. And his colleague, Frederick Lee, had died in 2015. And so I reached out to him. And I got even further intrigued when I talked to him. Let's take a quick break. And when we get back, there's still so much to discuss. Hi, I'm Danielle Robe, host of Bookmarked, the podcast by Reese's Book Club. And this week, we are talking about a monster.

Or maybe the woman who refused to be one. I'm sitting down with Maggie Jillon Hall to unpack her new film The Bride. And trust me, this isn't your grandmother's bride of Frankenstein. It's darker, smarter, sexier, a full reimagining of what happens when the monster gets a voice of her own. What I was more interested in was the monstrousness inside of each of us. You can spend your life running from those things, or you can turn around and shake hands with them. If I'm honest about that, and I tell my story about monsters really dealing in something truthful, and I do it in a way that's pop, that's hot, that's like getting on a roller coaster, will people respond?

Listen to Bookmarked, the Reese's Book Club podcast on the Iheart Radio app, Apple Podcasts, or wherever you get your podcasts. When you feel uncomfortable, what do you put on? Biggie. You put on Biggie when you feel uncomfortable? Because I want to get confident. This is DJ Hesterprin's Music is Therapy, a new podcast from me, a DJ and licensed therapist that asks one simple question. Who do you want to be? And what's the song that can take you there.

Music changes what you feel. And what you feel changes what you do, right? That moment where a song shifts something inside you, that's where transformation starts. I'm talking to experts across every area of life, like personal finance icon Gene Chatsky, New York Times journalist David Gellis, relationship legend Dan Savage, human connection teacher Mark Groves, and the man who sheet my ear more than anyone, Questlove. They'll bring the strategies. I'll pair them with the right records and will teach you how to use the music to make change stick. This isn't just a podcast. It's unconventional therapy for your entire year.

Listen to DJ Hester Prins' Music is Therapy on the IHeart Radio app, couple podcasts or wherever you get your podcasts. Ever feel like you're being chased by the marriage police. Welcome to boys and girls, the podcast where dating isn't dating. Arranged marriage is basically a reality show, except the contestants are strangers and your entire family is judging. You're sipping coffee with one maybe, grabbing dinner with another, and praying your Karmic Ken or Barbie appears before your shelf life runs out.

Trust me, I've been through this ancient and unshakable tradition. I jumped in, hoping to find love the right way, and instead I found chaos, cringe and comedy. And now, I'm looking for healing. Boys and Girls dives into every twist and turn of the arranged marriage carousel, the meat-awquard, the near-misses, the heartbreak, and let's not forget all the jokes. Listen to boys and girls on the IHard Radio app, Apple Podcasts, or wherever you get your podcasts.

Hi, it's Alec Baldwin. This season on my podcast, here's the thing I'm speaking with more artists, policymakers, and performers. My composer Mark Schaman. Once you've established that you have the talent, it's about the hang. It's the pleasure of hanging out with the people that you're with. You know, Rob and I was always a great hang. We would sit in kibbutz for hours and then eventually, get around to the music. That's what I mostly think of when I think of him, the time together laughing.

Lawyer at Robbie Kaplan. The great gift of being a lawyer is the ability to actually change things in our society in a way that very few people can. I mean, you can really make a difference to causes in the United States if you bring the right case at the right time. Marriage equality. Yeah, Windsor's the perfect example. And journalist Chris Whipple. Every White House staffer, they work in a bubble called the West Wing. And it's exponentially more so in the Trump white ass. Listen to the new season of Here's the Thing on the I-Heart Radio app or wherever you get your podcasts.

Hello, it's me, Anna Sinfield from The Girlfriends, the number one hit true crime show that puts women right in the center of their own stories. I'm back with more one-off interviews with some truly kick-ass women on The Girlfriend's Spotlight. I want to introduce you to Sylvia. I'm going to climb this. And then there's Fisaka. Let's see how we can stop killing and save lives. Layla dared to ask the question.

Is badness hereditary? And finally, we'll meet Rosamond. If it wasn't for the year where Ella lived, she wouldn't have died on that fatal night. You'll even get to meet my mum in that one, who I can always count on to keep my feet on the ground. I'm not too intimidated by her. What are you talking about?

Listen to the Girlfriend Spotlight on the IHeartRadio app, Apple Podcasts, or wherever you get your podcasts. Welcome back, everyone. I've been chatting with Lawrence and Gracia about his book, A Fatal Inheritance, how a family misfortune revealed a deadly medical mystery. Let's get back into things. You mentioned your journalist background. You're no stranger to investigating stories. and putting these stories together, but this was a very personal story for you as well. How was that process different?

Well, and first of all, I was a business journalist. I wasn't a science journalist. So I had never written about anything really personal about my family. I call this a journey of discovery and connection. And it was difficult at times, but also so rewarding. I think I learned more and I feel closer to my family. now that I have done all this research. And at the same time, I wore a different hat at different stages of the reporting, where I was just trying to understand the science, trying to make sure

I got it right, the genetics, because it's so much about genetics, trying to understand the history and the evolution of the understanding of cancer and the causes of cancer, because that really has changed over the decades since my mother died. And then try to make it a compelling story instead of a dry textbook story because in the end, this is about families. It's about families like mine and it's about loss, but it's also about love. In fact, I call this, you know, the book is as much a love letter to my families and families like mine as it is a book. I mean, that shines through so, so very clearly. I felt like I knew some of your family members By the end, I really loved that aspect of it.

And it's also so clear how much research went into this in terms of placing these discoveries in the broader context of what was happening in the history of medicine at the time. And I was wondering which sources you found to be particularly influential or helpful in this process. First of all, Dr. Frommini was exceptionally helpful. But Dr. Frommini had a lot of colleagues. One of the things I learned about science and scientific discovery is that there's really one person who does it all. It's often a team of scientists working together and sometimes working in competition who push knowledge forward.

So there are a lot of his colleagues, former colleagues, who were extraordinarily helpful. And also there were competitors who were working on some of the same efforts to try to identify these genes and, what they were doing and what the mutations might be doing. But in parallel, I also was helped extraordinarily by the family that was the focus of a lot of the early research. This family was so central and so helpful when I was finally able to reach them. And they really opened up. And I mean, to me, that was critical to telling the story of the medical mystery because my family wasn't a focus of the research. We learned about the condition and the mutation in our family decades later. This family, you know, kind of was a focus on the research from the beginning

of Liam Frommetti. I want to talk about this family and sort of their contributions that they made. But first, I want to take a step back and get this landscape, birds eye view of what cancer research was like at the time when this first family tree was being looked at. What was known about the cause of cancer and what were some of the prevailing hypotheses? Okay, so let's go back to the 1960s, and you really have to go back to that period in time. And cancer was not talked about a lot. Right. Kind of hushed tones.

And I think one of the reasons is that the prevailing theory at the time was that most cancers were caused by viruses. You think about that for a second. If cancers are caused by viruses, you maybe can catch cancer. So you don't really want to talk about it a lot that you have cancer in your family. Now, there were inklings that there might be environmental causes of some cancers. And there were some thinking that maybe certain types of cancers, especially site-specific cancers, like if you had a lot of breast cancer in your family, maybe, maybe that might be hereditary in some way,

although we don't really understand it. However, all the cancer experts believed that the vast majority of cancers, were caused by viruses. And most of the government research money was actually targeted efforts to identify viruses. Now, they weren't having any luck in doing that, but they kept spending and looking for that. And along come Lee and Falmini epidemiologists who are just curious about cases that are unexplained. They were young scientists at the National Cancer Institute. This is back in the mid to late 60s. When you say these were epidemiologists looking at patterns of cancer, what were they looking for and what were the cases that were catching their attention?

Well, I think they were particularly interested in childhood cancers. But what happened was in 1967, they came across a very unusual case. There was a father who was then 20-year-old's old who had leukemia. And much later, his 10-month-old son developed a soft tissue, rabdo, myosarcoma in his arm. Now, either of these cancers, the odds are very high against having. Having them father and son, the same family, I mean, it's astronomical. And so they were curious. Like, maybe we should take a look into this family. And when they began looking in this family, with the help of some of the family members, it was difficult because this is a sprawling family. You know, as many families in the United States, they're all over the country. They found a history. of cancer, all kinds of cancers at all ages, including other cancers among infants, going back five or six generations. And that was where they said, hmm, let's see if we can find a cause.

And they published a paper a couple of years later. It actually took quite a while to put together this family tree because they had to write to medical centers and get medical records. And it just, it took an enormous amount of time. And they added a few more families. to the study and they showed that there was a lot of cancers. They didn't know exactly why. In fact, their first paper that they wrote about it ended in a question mark that said, is this a familial syndrome? There was skepticism. The cancer expert said, ah, must be a virus that you just haven't been able to identify. Even though they had tested some tissues or viruses that hadn't been able to find anything. Or maybe it's an environmental factor that you haven't been

able to identify. Or, you know, actually more likely, it probably is just chance. I mean, you know, there are 100 million plus families in the United States. The odds are that if you are going to have a lot of cancers, and this just happened to be one of them. Being from any of like said, okay, look, we can't prove it. And they actually acknowledge that it could be one of those things. Although in their minds, they were, hmm, doesn't feel right. So they kind of said, we're not really so sure about that either. Eventually, this work seemed to build momentum. And there was more and more data that supported this hypothesis that maybe these cancers,

there is some sort of genetic or hereditary link to it. So what else were they finding? And how were they finding these other families? After their first paper was published, they got a little bit of attention. And other doctors who were coming across families would send them this information. So Lee and Fralmini began tracking more and more families over time. that were cancer prone. And every five to 10 years, they would publish another paper saying, hmm, we're finding more and more evidence that indeed these cancer prone families are

continued to have a high rate of cancer. One of the things that puzzled everybody, including them, but definitely the experts, was the fact that just like my family, there were all sorts of cancers, brain cancer, leukemia, you know, soft tissue cancer, lung cancer, breast cancer, bone cancer. And so the experts were like, these aren't related. How could that be hereditary? Again, it was against whatever knowledge existed. You know, even in cancer-prone families, cancers occur sporadically. It's not like they occur at regular intervals. There was more than a decade between my mother dying of cancer and my youngest sister than getting cancer. That was another thing that made it hard to speed up the research. But the understanding of genetics was

increasing dramatically in the 1970s and the technology that enabled scientists to look at individual genes and to study genes and find mutations. There also was an explosion in that equipment. And the combination of these things, things was critical. And the fact that Lee and Fralmani kept studying families, so they had a bigger pool of families, and very smartly, going back to the late 1960s with Family A, they collected tissue samples. So when they finally had the tools to examine the tissue samples, to look at individual genes, they could spot something that a decade or two earlier and certainly in the 1960s, would have been impossible.

And so there was many steps that had to be taken between recognizing this pattern in this very first in Family A, all the way to this becoming a named syndrome. What kind of led to those final pieces being put into place that led to Leiframani's syndrome being this clinical syndrome that can be defined and characterized? So in the late 1980s, they finally had the tools to look inside the genetic making, of these cancer families. Of course, humans have more than 20,000 genes. You know, kind of, where do we start looking? I mean, it's like, you know, kind of, it's like saying, hey, it's somewhere in Manhattan, but you have no idea where the address is,

you know, kind of there are millions of homes. So figuring that out, you know, where do we start looking? And this is a little bit where the knowledge of other scientists help them start focusing on where to start looking. So they had a few spot. where in studies of mice that they had found a particular gene that seemed to be present in many tumors. It's a gene called P53. And they actually thought that, hmm, this P53 must be a cancer-causing gene because it is so common in cancer. It's not all cancer tumors, but actually in more than cancer-causing.

half of cancer tumors, they found a mutation of P53. So they began focusing on P53, and once they started looking at the tissue samples of these family members, after a couple of years of study, they had their eureka moment. And the eureka moment was that in the tissues of the family members that had cancer, there was a mutation in P53. and that in the tissue members of family members who did not have cancer, and that same P53 gene, there was no mutation. The other aha moment was they realized that P53 wasn't causing a cancer. P53 is normally meant, and when it working properly, it stops cancer from occurring.

We all have our cells are dividing all the time. And most of those cell divisions are benign. Nothing happens. Occasionally, some of them are potentially malignant. And the amazing thing about the human body is that over millions of years of evolution, we have developed genes called cancer suppressor genes that are kind of search and destroying genes. They sense potentially cancerous cells. And they go and either repair that cell or they kill it so you don't get cancer. But if you have this mutation, they realize, it doesn't work properly. And your propensity, your chances of getting cancer are much higher. And this explains so much when they finally realized it. First of all, when I talked about how

pernicious this is, by age 40, if you are born with this mutation, this inherited mutation, you have a 50% chance of getting cancer. And often multiple cancers, if you survive your first, versus 5% in the whole population as a whole. The risk is 10 times higher. But it also explained why you would get cancers throughout the body. This P53, it turns out, was so important that it protected you from cancers throughout the body, except when it was mutated, it didn't. And this is in contrast to most cancer genes.

I mean, everybody, probably the best known cancer gene is the BRCA cancer gene, which helps you, prevent you from getting breast cancer and ovarian cancer to stuff. But it's really a site-specific. P-53 is a much broader gene and protects your whole body. And actually, since this discovery, and it was in late 1990 when it was announced, it was huge news, huge news in the scientific world. Not just in the scientific world. It was the front page of the New York Times, the Wall Street Journal had a big story. I mean, it was electrifying in the scientific.

P-53 has become the single most studied gene in the human body. It's called the guardian of the genome because it regulates cell growth and kind of helps prevent you from getting cancer. Let's take a quick break here. We'll be back before you know it. Hi, I'm Danielle Robe, host of Bookmarked, the podcast by Reese's Book Club. And this week, we are talking about a monster. Or maybe the woman who refused to be one.

I'm sitting down with Maggie Gyllenhaal to unpack her new film, The Bride. And trust me, this isn't your grandmother's bride. of Frankenstein. It's darker, smarter, sexier, a full reimagining of what happens when the monster gets a voice of her own. What I was more interested in was the monstrousness inside of each of us. You can spend your life running from those things, or you can turn around and shake hands with them. If I'm honest about that, and I tell my story about monsters really dealing in something truthful. And I do it in a way that's pop, that's hot, that's like getting on a roller coaster, will people respond.

Listen to Bookmarked, the Reese's Book Club podcast on the Iheart radio app, Apple Podcasts, or wherever you get your podcasts. Ever feel like you're being chased by the marriage police? Welcome to boys and girls, the podcast where dating isn't dating. arranged marriage is basically a reality show, except the contestants are strangers and your entire family is judging. You're sipping coffee with one maybe,

grabbing dinner with another, and praying your karmic ken or Barbie appears before your shelf life runs out. Trust me, I've been through this ancient and unshakable tradition. I jumped in, hoping to find love the right way, and instead I found chaos, cringe and comedy. And now I'm looking for healing. Boys and Girls dives into every twist and turn of the arranged marriage carousel.

The meat awkward, the near misses, the heartbreak, and let's not forget all the jokes. Listen to Boys and Girls on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. When you feel uncomfortable, what do you put on? Biggie. You put on Biggie when you feel uncomfortable? Because I want to get confident. This is DJ Hester Prince's Music is Therapy, a new podcast from me, a DJ and licensed therapist that asks one simple question,

who do you want to be and what's the song that can take you there? Music changes what you feel, and what you feel changes what you do, right? That moment where a song shifts something inside you, that's where transformation starts. This year, I'm talking to experts across every area of life, like personal finance icon Gene Chatsky, New York Times journalist David Gellis, relationship legend Dan Savage, Human Connection teacher Mark Groves

and the man who sheet my ear more than anyone, Questlove. They'll bring the strategies. I'll pair them with the right records and will teach you how to use the music to make change stick. This isn't just a podcast. It's unconventional therapy for your entire year.

Listen to DJ Hester Pryn's Music is Therapy on the IHart Radio app, Apple Podcasts, or wherever you get your podcasts. Hi, it's Alec Baldwin. This season on my podcast, here's the thing I'm speaking with more artists, policymakers, and performers. by composer Mark Shaman.

Once you've established that you have the talent, it's about the hang. It's the pleasure of hanging out with the people that you're with. You know, Rob and I was always a great hang. We would sit in kibbits for hours and then eventually get around to the music. That's what I mostly think of when I think of him,

the time together laughing. Lawyer of Robbie Kaplan. The great gift of being a lawyer is the ability to actually change things in our society in a way that very few people can't. I mean, you can really make a difference to causes in the United States if you bring the right case at the right time. Marriage equality. Yeah, Windsor's the perfect example.

And journalist Chris Whipple. Every White House staffer, they work in a bubble called the West Wing. And it's exponentially more so in the Trump White House. Listen to the new season of Here's the Thing on the I-Heart Radio app or wherever you get your podcasts. Hello, it's me, Anna Sinfield, from the government. The number one hit true crime show that puts women right in the center of their own stories. I'm back with more one-off interviews with some truly kick-ass women on the girlfriend's spotlight. I want to introduce you to Sylvia.

I'm going to climb this. And then there's Fasaka. Let's see how we can stop killing and save lives. Leila dared to ask the question. Is badness hereditary? And finally, we'll meet Rosamond. If it wasn't for the year where Ella lived, she wouldn't have died on that fatal night.

You'll even get to meet my mum in that one, who I can always count on to keep my feet on the ground. I'm not too intimidated by her. What are you talking about? Listen to the Girlfriend Spotlight on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Welcome back, everyone.

I'm here chatting with Lodaghd You. Lawrence and Gracia about his book of fatal inheritance. Let's get into some more questions. I mean, the discovery, and you illustrate this so clearly in your book, too, that this discovery was revolutionary for understanding the mechanism underlying so many different cancers. And it's fascinating to talk about how, okay, this guardian gene can get disrupted in our germline cells, but then also there can be disruptions later on. And so how did this sort of change our understanding or help us to formulate this two-hit hypothesis. There are two kind of mutations. One is a germline mutation. That is something that you're

born with. You're inherited. So it's in every cell in my body. So also what's called a somatic mutation. It's like a sporadic mutation. So again, our cells are dividing constantly and mutating constantly. And even if you don't have an inherited mutation in P53, if you have this sporadic spontaneous mutation post-birth in P53, that breaks down your body's ability to fight cancer, which explained why you've had so many cancers with P-53 mutations, even in people who didn't have an hereditary center. So, you know, the understanding of how this mechanism works help doctors start saying, what can we do to try to target medicines to help prevent cancers? Now, of course, that's turned out to be very difficult because fixing B53 or any other mutation is very difficult.

But you can have the ability to look for that mutation. This was one of the breakthroughs. If you know that you have that mutation, you can screen for cancers and try to catch them early. And the best defense against cancer is to catch it early. And so this was one of the great advantages of learning this. and it doesn't stop you from getting cancer. But you can identify it early on if you know that it's in your family.

It can help you live a much longer life. Right. Be a little bit proactive in some respects, even though we may not have a direct treatment or cure for the underlying cause. Right. When Lee-Framani syndrome was named and described, and when this P53 discovery was made, I'm curious to know the impact of these developments on the families themselves,

that were involved in these early family trees, this early research, what did it mean to them to have this answer? I think the most important thing is that they finally knew the cause. I mean, for a long time, the family members are dying. They figure something must be wrong. For a while, they thought it might be environmental. Knowing they had it was, I wouldn't say a relief, but when you're looking for an explanation, knowing is something that is very helpful. But, kind of go back to the 90s, especially in the early 90s, where they're saying, okay, now we know this. What can we do with this? And early on, there wasn't a lot they could do it.

We could do more research to try to figure out what we can do with this. And I think so for the families, particularly Family A, it was helpful to know this, but it was like, you can't help us now that you know this. And they were like, well, no, but we're hoping that we'll be able to help you some point in the future. So I think it was hard for them. In fact, so not long after the discovery of P53, and this is the cause of Lee from Mini syndrome, all these cancers in your family.

One branch of Family A, the father got brain cancer. He was in his early 30s. And within a year, his 10-year-old son also got brain cancer. And they both died within the year. Nothing could be done to help them. I think so some of the family members felt maybe I don't want to know. I mean, some of them did want to get tested to know that they had it and figure out what to do, but other family members where you can't help me if I know it so, you know, they kind of

pulled back a little bit. I think it's understandable. So the other thing is, if you have this mutation in your family, there's a 50-50 chance of each child inheriting it. So you have branches of the family that are riddled with it because it was passed on. And then you have other branches of the family that are cancer-free, which is also difficult and can cause pain and tension within families too. And I think that was part of the reason why some of the family members just felt, come back to me and let me know when you can, you have information that this can help me,

as opposed to just scare the daylights out of me and, you know, be worried all the time that I'm going to have cancer. It is certainly a dilemma. And in testing for many different genetic diseases and disorders, what do we do with that knowledge? What does that knowledge give us? And some people may feel empowered by that or like you said, it can help with screening and in preventative ways, but ultimately does it change an outcome?

It's a hard thing to weigh. It's a very personal decision. And while I think that knowledge is power and you want to know, I also understand why some people say, hey, I think I'd prefer not to know. Yeah, I absolutely can understand both perspectives. And I'm curious to know, when did you first learn about Lee Framani syndrome? Let's go back again to 1990 in this discovery, big news. By that time, my brother and I were both senior editors at the Wall Street Journal.

Our two sisters and mother died and his son had had cancer. I don't think we ever talked about this discovery. And it was odd. We didn't say, oh, my God, that must be us. The reason is, I think there were a couple of reasons. First of all, our father was a research chemist. And we had this supposition for a long time that he must be inadvertently coming home with tiny particles of chemicals on his clothing. We're ingesting it.

Years later, this ends up being cancer. So we had our theory about what was causing a cancer. And the other thing is that doctors never suggested to us that it might be hereditary. For a long time, Leifarmini syndrome is so rare. all the cancers are different, a lot of doctors weren't aware of it, they certainly wouldn't have suggested it. And another reason they wouldn't have suggested it to us is that our mother was the first in our family to have cancer. There wasn't a long history of cancer in our family, their way that there was with family A. So fast forward, in 2014, my nephew had had had his second cancer, and my brother had

had another couple of cancers. Fortunately, they both had survived those. And his doctor finally said, you know, you've got this pattern. It might be hereditary. I think you should get tested. My brother called me up. And this was the first I'd ever heard of P53 or Leafrowmini, although I didn't do anything about it. And he said, I'm going to get tested for this mutation. And sure enough, a month later, 2015, he sent me a note saying, I tested positive. And he said, you know, actually, it's a relief. Now, I know. And he had caught all his cancers early, but then he started to do even more rigorous screening. I didn't immediately go out and get tested. I was at that point in my early 60s, and I was figured, I don't have anything to worry about.

But my daughter, I have two children. My daughter finally prevailed on me. She says, Dad, you really should get tested. I want to know. So it turns out that there was a value of knowing. I didn't really realize this at the time. But if you have Leframani syndrome, you have this inherited P53 mutation. There's a 95% chance in your lifetime of getting cancer. Staggering. But there's a 5% chance that you won't. So I could have been a carrier.

I could have the mutation, but be in that 5% and still have passed it up. So the value in getting tested was having that certainty. So I got tested and tested negative for the mutation. So this also explained why I had been spared while my siblings had not. And I distinctly remembered, and it was just one of those moments that you never forget. It's etched in your memory. I sent an email to my brother and said, I tested negative. And again, it can be hard for some family members to know that they have it and his son had cancer and that other family members don't have it.

And I've seen it to cause a strain. And it's understandable. That's not unusual or abnormal reaction, actually. Instead, my brother sent me back a two-word email response with exclamation points. Great news. He was happy for me. He never said, why me? Why not you?

This is not fair. People ask me a little bit, do you feel survivor's guilt? And for whatever reason, I don't think I feel survivor's guilt, or at least it's not heavy on me. And I think there are two reasons. One, I guess I'm rational enough to say, this is genetics. There was a 50-50 chance for me to get this. I didn't get it.

And the other thing, I think I probably would have felt a bit worse of our results if my brother had reacted in a different way. And so that was another, those ultimate brotherly love, things that really kind of helped a lot in this journey. As you write about, you two had this really special and best friend relationship. I'd love to hear more about this relationship that you had with your brother. We were both journalists. He was at the Wall Street Journal many years.

He went up for his coverage of the auto industry. I've had a been lucky to have a great career too. And I think the fact that we worked together and knew a lot of the same people, in fact, it's funny. A lot of siblings have friends in childhood who are the same friends. We play different sports and we did different things, even though we're two years apart, we didn't have a lot of. friends in common in childhood. But in our adulthood, we have a lot of friends in common. So I think

that was one reason that we were particularly close. And I think inevitably close because we lost our mother and both our sisters. Our father also died pretty young. He was 59, although he didn't have cancer. He had a heart condition. You know, when you're the last surviving member of your family, you've got those shared memories. So you think about it. Your oldest memories, your longest memories are from childhood and growing up together. And so I think it was a combination of that, our loss being in the same business. We're very close. In fact, I write in the book, occasionally I'll come across people who say that they are estranged

from their siblings. They haven't talked to their siblings for five or ten years or only see them on rarest occasions. And I'm like, do you know how lucky you are to have your siblings? I mean, most people I know have either all or most of their siblings at my age. I don't have any of my siblings. And it really kind of pains me. And, you know, I've had a couple of people after reading the book reach out to me and say, you know, I read that.

And I've reached out to my sibling. And yeah, I thought I was right and they were wrong or whatever. But I realized that in the end, that doesn't matter. What matters is that we reconnect. That's been one of the unexpected but nice side effects of writing the book. You paint such a beautiful picture, it's such a clear picture of your siblings and of your mom as well and your experience with watching them and being witness to their illness and then ultimately them passing. And I felt like I knew many of your siblings just from the beautiful way that you wrote

about them. And I was wondering if you could tell me a bit more about your mom and your sisters. And there's one moment in particular in your book that really has stuck with me so much, which is when you were reaching out to your sisters, one of your sister's doctors, and he remembered her right away. My sisters died in the 1980s. It's four decades ago. And I wanted to know more. Obviously, I knew a lot about it.

But I wanted to talk to their friends to figure out from their perspective. And one of my sisters have been married. She didn't have any kids. And this was, again, feeling of closeness. So one of my sisters, Gina, who died at 32, kept a diary. from the time that she learned about having cancer until the times that she couldn't anymore. And she died within about six months. And reading about her hopes and fears initially starting out, very hopeful that this could be overcome.

If only she would fight it strongly enough, if only she had enough willpower. I mean, that was hard to read because, you know, knowing what I know now, it's like it had nothing to do with whatever willpower. She was putting in on herself to cure herself. It was like, oh, my gosh, it doesn't have anything to do with that. You have inherited this mutation, that is a deadly mutation. And I definitely was brought to tears. But the moment, probably the single moment, most unexpected and most part tears was what you mentioned about my sister Angela, who was 24 when she died.

Again, I was hoping to talk to her doctor, and I didn't know exactly who her doctor was. I had an idea. I was talking to my sister-in-law, who's my brother's wife, and she thought, you know, kind of maybe this was his last name. And I knew he was in Chicago. And so I set up a message on LinkedIn to this doctor in Chicago and said, hey, I don't know if you would remember, but my sister died of cancer in the early 1980s in Chicago. You were an ecologist then. And I think you might have. I'd like to talk to you if you were. But of course, I'm sure you've treated a lot of patients and may not remember her. And we're kind of going back decades.

Within a couple of hours, I got an email from Dr. Locker. And the email subject line was, I have never forgotten your sister. And I can tell you, I just sat there and my eyes welled up. I was like my breath was taken away. And so Angela, again, just 24 years. old, before she died, but knowing that she was dying, had arranged to have flowers sent to us her siblings, to her friends, and to her caregivers after she died. And the flowers arrived with a one-word message forward. And Dr. Locker had never forgotten that. He said,

I've never forgotten that. He says, to this day, I can remember her face. I can see her and I can see those flowers. And, you know, I thought what an amazing young woman, what amazing women she could have grown to be, to have thought to do that at that young age. I mean, it's just kind of remarkable. And, you know, I talked to her friends and some of her other friends had received it

and I said it was like so, so like Angela to do that. I encourage everybody to try to make these journeys of discovery. Talk to your relatives about important times. in your life, talk to your aunts and uncles, grandparents, while you can, while you're here. I wish I had done more of that before I wrote this book. But these memories are so precious to me. And I think they're precious to everybody. In fact, can I read just one paragraph from the book? Please. Please. Yeah. Because I think it explains a little bit. I wanted to tell the story about my family. It's important to tell the story about these other families. I wanted to honor the

doctors, dedicated doctors, who again, against all odds and being discouraged of doing it. And I was writing the last chapter in the book. And occasionally when you're writing, a lot of times you're thinking about every paragraph and you're writing and rewriting, and occasionally something just kind of flows out. And this flows out when I had in the last chapter describing this interaction with Dr. Locker and the flowers. When we are gone, we live on in memories. Those memories can remain surprisingly vivid for a long time, the people whose lives we have touched. However, briefly, I was moved that Dr. Locker still treasured memories of Angela, but I know memories invariably can fade and even be lost when

the people whose lives we touched are themselves gone. So while this is a book about scientific discovery begun by two tireless doctors, it is even more a love letter to my family written to preserve memories for my children and their children and the children after them, because I will be gone someday as well, and I don't want these memories to be gone with me. It's so beautiful. It's such an important message and a beautiful tribute to your family, and it's so meaningful because what we don't do often enough, I think, in science is to humanize these discoveries and show the direct impact that it has on people's lives. on their loved ones as well. And I think that is what you have done so wonderfully with your book.

Thanks for those words, Aaron. I think these doctors also, I mean, they wanted to make this great discovery, but I think they were driven by what can they do to help people too. And that was really, really important. And in the intervening years, many of the doctors who worked with Dr. Lee and Frommany have continued their work. You know, what more can we learn about P53 and one of their colleagues, Dr. David Malkin, who was very young at the time, helped discover the P53 gene, has created this protocol, this screening protocol that is very valuable in helping to prolong lives. And there is a association, the Lee from Any Syndrome Association, that helps families both cope with living with this, but also furthering research. And so, but it is about families. It centers on

the families and the doctors who tirelessly, tirelessly kept out. after this. I don't think we can thank them enough. And the other thing is that I learned that we tend to think that scientific discovery happens like that. It's slow. It's halting. It's often goes down a wrong path before it gets on the right path. It takes time. It takes money. It takes collaboration. And without that, where would we be? These families, there still is no cure, but they are a lot better off knowing and kind of having the screening protocol and all. And, you know, I've heard from so many people. That's one of the things unexpected, reaching out to me, you know, saying, your family is my family.

People feeling that they're isolated. Nobody understands what we are going through. And I've really been moved by that. Now we can give this to friends or our friends can read it and they get a sense of just how devastating this syndrome has been for us. And again, it's not a matter if you have this. mutation. It's not a matter of if you're going to get cancer, but it's when and how often you're going to get cancer. And so to the extent that I can raise awareness and help these families, that's the most important thing for me. Well, I have really, really enjoyed chatting with you

today. It has been such a meaningful conversation, and I appreciate so much you taking the time. Thank you. And to all the families, I hope you can persevere. And I, love each other as you go through this difficult time. A big thank you again to Lawrence and Gracia for taking the time to chat with me. This was such a moving conversation and so especially important in light of all the cuts to cancer research funding in this country. If you enjoyed today's episode and would like to learn more, check out our website, This Podcast Will Kill You.com, where I'll post a link to where you can find a fatal inheritance,

how a family misfortune revealed a deadly medical mystery, as well as a link to Larry's website where you can find his other work. And don't forget, you can check out our website for all sorts of other cool things, including but not limited to transcripts, quarantini and placebo-rida recipes, show notes and references for all of our episodes, links to merch, our bookshop.org affiliate account, our Goodreads list, a firsthand account form, and music by Bloodmobile. Speaking of which, thank you to Bloodmobile for providing the music for this episode

and all of our episodes. Thank you to Leanna Squalachi and Tom Bri Fogle for our audio mixing. And thanks to you listeners for listening. I hope you liked this episode and our loving being part of the TPWKY Book Club. And a special thank you, as always, to our fantastic patrons. We appreciate your support so very much. Well, until next time, keep washing those hands. Hi listeners, I'm Anistonfield, the host of The Girlfriend Spotlight,

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