Pod Insights This Podcast Will Kill You Special Episode: Lawrence Ingrassia & A Fatal Inheritance About this episode 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 http://www.larryingrassia.com/ 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 https://bookshop.org/a/3175/9781250837233, 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.
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0:01 Speaker 00 This is Exactly Right.
0:06 Speaker 00 This is Troy Millings. If you travel for work like I do, you know every trip is an opportunity to get more from the miles you're already earning. Whether you're heading to your next client meeting or catching a flight home, those miles can go a long way. For a limited time, new Delta SkyMiles Business Card members can earn 200,000 bonus miles, the highest miles offered this year with the Delta SkyMiles Reserve Business American Express Card. Apply today at www.deltacom/podcast. Offer ends November 4th, 2026. Minimum spending requirements and terms apply.
0:40 Speaker 01 This is Stugatz from Stugatz and Company Live. Buy smart, drive for less, and trade for more. That's Toyota affordability. And it all starts with a great deal on an all-wheel-drive Camry, Corolla Cross, or a Corolla Sedan with the latest features and tech, or test drive a spacious Grand Highlander or adventure-ready RAV4. And with so many hybrid models available, you can enjoy longer trips without all the stops. While Toyota's legendary resale value means you can get more at trade-in. Get a great deal today and a great value tomorrow. Shop toyota.com for deals and details. Toyota, let's go places.
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2:32 Speaker 03 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, thispodcastwillkillyou.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.
3:17 Speaker 03 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
4:02 Speaker 03 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 mourn this painful loss.
4:48 Speaker 03 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 Ingrassia. 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 Fraumany, uncovered a key piece of the cancer puzzle, the P53 gene, when a family suffered heartbreaking loss after heartbreaking loss to cancer. For Ingrassia, 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.
5:33 Speaker 03 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, Ingrassia 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, Ingrassia 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,
6:16 Speaker 03 so let's take a quick break and get into it.
6:42 Speaker 03 Larry, thank you so much for joining me today.
6:45 Speaker 04 It's my pleasure, Erin.
6:47 Speaker 03 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?
7:14 Speaker 04 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 amputating his leg and hip.
7:52 Speaker 04 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 Leuveni 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,
8:37 Speaker 04 I knew I was meant to write.
8:40 Speaker 05 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?
8:51 Speaker 04 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.
9:13 Speaker 04 Along with the story of the researchers, dedicated researchers who spent years, actually decades before they they solved the mystery, and that actually was part of the thing that intrigued me about the book and and the whole condition is 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 pernicious. 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
9:57 Speaker 04 medical mystery, Joseph Brawmey 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.
10:12 Speaker 03 Let's take a quick break. And when we get back, there's still so much to discuss.
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11:32 Speaker 06 Hey, it's Lunchbox from the Bobby Bones Show. Buy smart, drive for less, and trade for more. That's Toyota affordability, and it starts with a great deal on an all-wheel-drive Camry, Corolla Cross, or a Corolla Sedan with the latest features in tech. Or test drive a spacious Grand Highlander or an adventure-ready RAV4. And with so many hybrid models available, you can enjoy longer trips without all the stops, while Toyota's legendary resale value means you could get more at trade-in. Get a deal today and great value tomorrow. Shop toyota.com for deals and details. Toyota, let's go places.
12:10 Speaker 07 Hello, hello. I'm Malcolm Gladwell, host of Smart Talks with IBM. Imagine your business depends on a system you didn't build and don't fully control. For years, it works perfectly. It's fast, reliable, affordable, so over time, more and more of your operations rely on it. Then one day, the terms change. What once felt flexible now feels difficult to leave. Moving to another provider or bringing those capabilities back under your own control could take years, cost millions, and disrupt the business in the process. That's the challenge of digital sovereignty. Businesses today rely on all sorts of third-party systems: cloud platforms, data pipelines,
12:55 Speaker 07 AI models, software tools. Most days, these systems operate quietly in the background, but when something changes, like costs go up or rules shift, organizations are forced to confront how much control and flexibility they actually have. So to understand the challenge up close, I traveled to Paris to speak with IBM's Anapaula Assis and acts as CIO, Giovanni Daniele, two people who think about these questions every day. Hear the full conversation at ibm.com/smarttalks or wherever you get your podcasts.
13:50 Speaker 05 Welcome back, everyone. I've been chatting with Lawrence Ingrascia 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?
14:15 Speaker 04 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
14:56 Speaker 04 of the understanding of cancer and the causes of cancer, because that really has changed over the decades since my mother died. And then trying 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.
15:27 Speaker 05 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.
15:57 Speaker 04 First of all, Dr. Fraumany was exceptionally helpful. But Dr. Fraumany 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 were 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.
16:36 Speaker 04 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 Fraumany.
17:15 Speaker 05 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, bird's 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?
17:35 Speaker 04 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.
17:44 Speaker 05 Right.
17:45 Speaker 04 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. If 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 a lot that you have cancer in your family. Now, there were inklings that there might be. Environmental causes of some cancers. And there was 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.
18:30 Speaker 04 And most of the government research money was actually targeted to 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 Fowmene, epidemiologists, who are just curious about cases that are unexplained.
18:51 Speaker 05 Mm-hmm.
18:52 Speaker 04 They were young scientists at the National Cancer Institute. This is back in the mid to late 60s.
18:57 Speaker 05 When you say thieves were epidemiologists looking at patterns of cancer, what were they looking for and what were the cases that were catching their attention?
19:06 Speaker 04 Well, they 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 years old, who had leukemia. And much later, his 10-month-old son developed a soft-tissue rhabdomyosarcoma 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.
19:51 Speaker 04 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.
20:13 Speaker 04 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 experts said, ah, must be a virus that you just haven't been able to identify. Even though they had tested some tissues for viruses and hadn't been able to find anything. Or maybe it's an environmental factor that you haven't been able to identify.
20:57 Speaker 04 Or, you know what, 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 our few are going to have a lot of cancers and this just happened to be one of them. Leon Fraumany said, okay, look, we can't prove it. And they actually acknowledged 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.
21:25 Speaker 05 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?
21:42 Speaker 04 After their first paper was published, it got a little bit of attention and other doctors who were coming across families would send them this information. So Leon Fraumany 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 continuing 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.
22:26 Speaker 04 And so the experts were like, hmm, these aren't related. How could that be hereditary? Again, it was against whatever knowledge existed.
22:37 Speaker 04 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 then 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.
23:20 Speaker 04 And the combination of these things was critical. And the fact that Lee Fromany 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.
23:54 Speaker 05 And there, 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 that, those final pieces being put into place that led to Lee Fromany syndrome being this clinical syndrome that can be defined and characterized?
24:16 Speaker 04 So in the late 1980s, they finally had the tools to look inside the genetic makeup 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 helped them start focusing on where to start looking. So they had a few spots where in studies of mice that they had found a particular gene
24:59 Speaker 04 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 cancers. Not all cancer tumors, but in actually in more than 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.
25:42 Speaker 04 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, in that same P53 gene, there was no mutation. The other aha moment was they realized that P53 wasn't causing the cancer. P53 is normally meant, and when it's working properly, it stops cancer from occurring. Well, we all have, our cells are dividing all the time. And most of those cell divisions are benign. Nothing happens.
26:27 Speaker 04 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 destroy 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,
27:08 Speaker 04 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 one versus 5% in the whole population as a whole. Your 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, prevents you from getting breast cancer and ovarian cancer and stuff. But it's really a site specific.
27:51 Speaker 04 P53 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, you know, of the New York Times, the Wall Street Journal had a big story. I mean, it was electrifying in the scientific. P53 has become the single most studied gene in the human body. And it's called the guardian of the genome because it regulates cell growth and kind of helps prevent you from getting cancer.
28:27 Speaker 03 Let's take a quick break here. We'll be back before you know it.
28:32 Speaker 00 This is Troy Millings. As someone who travels a lot for work, I really appreciate a premium airport experience. With the Delta SkyMiles Reserve Business American Express Card, it truly feels like you can have it all. For a limited time, new Delta SkyMiles Reserve Business Card members can earn 200,000 bonus miles, the highest miles offered this year. Card members can also enjoy 15 visits to the Delta Sky Club each medallion year when flying Delta, and you can unlock unlimited Delta Sky Club access after spending $75,000 in purchases on your card during a calendar year. Those are benefits you can get behind. You also get four one-time guest passes each medallion year, so you can bring a friend or colleague along.
29:16 Speaker 00 15 Sky Club visits plus four guest passes? That's up to $950,000 annual value. Value estimate based on a $50 per visit rate to purchase additional visits or bring a guest to the Delta Sky Club. It's the kind of premium access that helps you feel right at home and at ease, no matter where you're headed. Apply today at www.delta.com/podcast. Offer ends November 4, 2026. Minimum spending requirements and terms apply.
29:46 Speaker 01 This is Stugatz from Stugatz and Company Live. Buy smart, drive for less, and trade for more. That's Toyota affordability. And it all starts with a great deal on an all-wheel-drive Camry, Corolla Cross, or a Corolla sedan with the latest features, Entec. Or test drive a spacious Grand Highlander or adventure-ready RAV4. And with so many hybrid models available, you can enjoy longer trips without all the stops. While Toyota's legendary resale value means you can get more at trade-in. Get a great deal today and a great value tomorrow. Shop toyota.com for deals and details. Toyota, let's go places.
30:25 Speaker 07 Hello, hello. I'm Malcolm Gladwell, host of Smart Talks with IBM. Imagine your business depends on a system you didn't build and don't fully control. For years, it works perfectly. It's fast, reliable, affordable. So over time, more and more of your operations rely on it. Then one day, the terms change. What once felt flexible now feels difficult to leave. Moving to another provider or bringing those capabilities back under your own control could take years, cost millions, and disrupt the business in the process. That's the challenge of digital sovereignty. Businesses today rely on all sorts of third-party systems: cloud platforms, data pipelines,
31:10 Speaker 07 AI models, software tools. Most days, these systems operate quietly in the background. But when something changes, like costs go up or rules shift, organizations are forced to confront how much control and flexibility they actually have. So to understand the challenge up close, I traveled to Paris to speak with IBM's Annapola Assis and Acts as CIO, Giovanni Daniele, two people who think about these questions every day. Hear the full conversation at ibm.com/smarttalks or wherever you get your podcasts.
32:04 Speaker 05 Welcome back, everyone. I'm here chatting with Lawrence Ingraccia about his book, A 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 germ line 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?
32:40 Speaker 04 There are two kinds of mutations. One is a germ line mutation. That is something that you're born with. You're inherited. Okay, so it's in every cell in my body. So I also know what's called a somatic mutation. It's like a sporadic mutation. So again, our, 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 P53 mutations, even in people who didn't have an hereditary syndrome.
33:22 Speaker 04 So, you know, the understanding of how this mechanism works helped 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, 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.
34:08 Speaker 04 It can help you live a much longer life.
34:10 Speaker 05 Right, be, be a little bit proactive in, in some respects, even though we may not have a direct treatment or cure for the underlying cause.
34:19 Speaker 04 Right.
34:19 Speaker 05 When Lee-Fra Mani syndrome was named and described, and when this P53 discovery was made, I'm, I'm curious to know the impact of these developments on the families themselves that were involved in these, these early family trees, this early research. What did it mean to them to have this answer?
34:39 Speaker 04 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, 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 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 with 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?
35:23 Speaker 04 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, it was hard for them. In fact, so not long after the discovery of P53, and kind of this is the cause of Lee-Fraumeni syndrome, all these cancers in your family. One branch of Family A, a 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 a 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 were, you can't help me if I know it. So, you know, they kind of pulled back a little bit. And I think that's understandable.
36:08 Speaker 04 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.
36:50 Speaker 05 It is certainly a dilemma 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.
37:10 Speaker 04 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.
37:22 Speaker 05 Yeah, I absolutely can understand both perspectives. And I'm curious to know, when did you first learn about Le Fanuori syndrome?
37:31 Speaker 04 Let's go back again to 1990 and 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, you know, 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 the cancer.
38:16 Speaker 04 And the other thing is that doctors never suggested to us that it might be hereditary. For a long time, Le Fanuori 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, the way that there was with family A. So, fast forward, in 2014, my nephew had had his second cancer, 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.
39:00 Speaker 04 I think you should get tested. My brother called me up, and this was the first I'd ever heard of P53 or Leukaemia. 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, 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 is a value of knowing.
39:46 Speaker 04 I didn't really realize this at the time, but if you have Leukaemia 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 on. 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.
40:31 Speaker 04 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. It causes 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. You know, 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.
41:16 Speaker 04 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 if my brother had reacted a different way. And so that was another of those ultimate brotherly love, things that really kind of helped a lot in this journey.
41:34 Speaker 05 As you write about, you two had this really special and best friend relationship. But I'd love to hear more about this, this relationship that you had with your brother.
41:44 Speaker 04 We're both journalists. He was at the Wall Street Journal many years. He won a Pulitzer Prize for his coverage of the auto industry. I've had a, been lucky to have a great career too. And I think kind of 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. Well, we played 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, 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 at pretty young. He was 59, although he didn't
42:26 Speaker 04 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's a combination of that, our loss, being in the same business, we're very close. In fact, I, 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 10 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
43:07 Speaker 04 age. I don't have any of my siblings. And it just, 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.
43:36 Speaker 05 You, you paint such a beautiful picture, it's such a clear picture of your siblings and of your mom as well, and, and your experience with watching them and being witness to their illness and then ultimately them passing. And it, I felt like I, I knew many of, 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.
44:12 Speaker 04 My sisters died in the 1980s. It's, you know, 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 had 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 till 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.
44:56 Speaker 04 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. See, I wish she was putting it on herself to cure herself. And it's 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 brought to 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.
45:36 Speaker 04 And I knew he was in Chicago. And so I set up a message, 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 oncologist 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."
46:16 Speaker 04 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."
46:56 Speaker 04 He says, "To this day, I can remember her face and I can see her and I can see those flowers." And, you know, I thought, what an amazing young woman, what amazing woman 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.
47:38 Speaker 04 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?
47:48 Speaker 05 Please, please, yeah.
47:49 Speaker 04 Because I think it explains a little bit. I wanted to tell the story about my family. It was 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 into doing it. And I was writing the last chapter of the book, and you know, occasionally when you're writing, a lot of times you're thinking about every paragraph, then you're writing and rewriting, and occasionally something just kind of flows out. And this flowed 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 through the people whose lives we have touched, however briefly.
48:32 Speaker 04 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.
49:04 Speaker 05 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 and on their loved ones as well. And I think that is what you have done so wonderfully with your book.
49:31 Speaker 04 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 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 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.
50:14 Speaker 04 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 are isolated. Nobody understands what we are going through. And I've really been moved by that. Now we can give this book to friends, or our friends can read it, and they get a sense of just how devastating this syndrome has been for
50:55 Speaker 04 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 love each other as you go through this difficult time.
52:09 Speaker 03 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, thispodcastwillkillyou.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 Rita recipes, show notes and references for all of our episodes, links to merch, our bookshop.org affiliate account, our Goodreads
52:54 Speaker 03 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 Liana Scolacci and Tom Bryfogle for our audio mixing, and thanks to you listeners for listening. I hope you liked this episode and are 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.
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Previous Ep 203 Cancer Part 2: Why does it happen? Next Ep 204 Cancer Part 3: How do we treat it? Page updated October 31, 2026 · transcript and summary are machine-generated
