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'A Fatal Inheritance' follows a family's struggle with cancer across generations

SCOTT SIMON, HOST:

It may be hard to imagine a family in America that hasn't been wounded by cancer. The losses in Lawrence Ingrassia's family have been extraordinary. His mother, Regina, died of breast cancer when she was 42. Larry was 15. His sister Angela died about a decade later of abdominal cancer at the age of 24. And his nephew Charlie got cancer in his cheek when he was just 2. His sister Gina was lost to lung cancer when she was 32. And his brother Paul, also then working for The Wall Street Journal, had to contend with several different cancers for more than 20 years.

The loss, pain and incomprehension has sent Larry Ingrassia on his search to try to find some scientific thread through these unfathomable losses. His new book is "A Fatal Inheritance: How A Family Misfortune Revealed A Deadly Medical Mystery." And Lawrence Ingrassia, former managing editor of the Los Angeles Times and deputy managing editor of The New York Times, as well, joins us from New York. Larry, thanks so much for being with us.

LAWRENCE INGRASSIA: It's my pleasure, Scott.

SIMON: You know, when I read your memoir, I had to contend with the fact that I've known many people who've died of cancer. I've done obituaries for many people who've died of cancer. I'm not sure I really know what cancer is. Do we really know what it is and what causes it?

INGRASSIA: You know, that's a great question. If you go back a half-century, you know, or a little bit more to the 1960s, cancer was very, very deadly back then. Don't get me wrong, it still is a terrible killer. But there's been a lot of progress, particularly with some kinds of cancer. You know, now so much has been learned about cancer. I learned in this journey of discovery that I went on that two of the main pioneers, two young doctors at the National Cancer Institute who stumbled across a family like mine that had a lot of cancers, all different kinds of cancers, all different ages - they were determined to figure out what was going on. Now it took them a long time, more than 20 years, but they did. And, you know, I consider them two heroes - Fred Li and Joe Fraumeni.

SIMON: What did Frederick Li and Joseph Fraumeni develop, uncover, discover, establish that had been missing?

INGRASSIA: Around the time my mother was ill - this is in the late '60s - they came across this family. Initially, there was a father who was 23 years old who had leukemia and a 10-month-old son who had a soft tissue cancer in his arm called rhabdomyosarcoma. Both of these are pretty unusual for those ages, but the combination of that in a father and son was - the odds against it we astronomical. And as they started looking at this family, they said, you know what? The pattern here seems - maybe there is something hereditary going on there. So it took more than 20 years, and a lot of other pioneers joined in in the search for the genetic cause of the cancer.

And lo and behold, in 1990, late 1990, they discovered a mutation and a gene that turns out to be hugely important. It's called p53. It's a cancer suppressor gene. So we all have cells that are constantly mutating. But the good thing that we have is that we have cancer suppressor genes. BRCA, the breast cancer gene, is probably the best known. But p53 - it is kind of on a search and destroy mission. This gene will find potentially cancer cells anywhere in the body and will kill or repair potentially cancerous cells from becoming malignant. That's great, except if you're born with the mutation in p53, and that was the miracle moment.

And this opened up not just an understanding of hereditary cancer but broadly of, hey, how cancer can be caused when you have mutations in cancer suppressor genes. That's one of the things. So this really was a huge moment. I didn't realize it. It turns out The New York Times ran a two-column story at the top of page one. The Wall Street Journal ran a four-column story. You know, that's where my brother and I were working. Somehow, we missed it. Again, that was because we were thinking it's something with - had to do with all the chemicals that our father was taking home.

SIMON: Because your father worked as a scientist.

INGRASSIA: Yes. But you really have to give credit for Li and Fraumeni for persisting, for being determined, for showing a dedication, even though there was a lot of skepticism early on about their research.

SIMON: I've got to ask. What was it like to do this book?

INGRASSIA: You know, Scott, it was painful. But also, I would have to say it was rewarding. My brother and I were always close, especially because we were the only ones left, and he died a few years ago. But I knew a lot about my sisters and their cancers, but I learned so much more as part of this journey of discovery that I went on. For example, my sister. Her husband shared with me the diary that she had kept from the moment she learned that she had cancer, and it was painful to read. This was back in the '80s when there was a lot of belief that, you know, just positive thinking, you know, could cure whatever ailed you, right?

And I'm reading this, and I'm thinking, Gina, you had this deadly mutation. There was nothing that you could have done. I was thinking back, you know, my mother being ill all those years and dying at 42 with four young children. And, you know, as a parent, you want to see your children grow up. Oh, my God, how - as hard as being ill was for her, how hard that must have been that she was not going to have that life with her children. And so kind of for me, looking back, you know, we're here, and we're gone. And while we're here, make the most of those connections that you have with people. That's what everybody is going to remember.

SIMON: After all you've learned, what you've discovered - and I ask this question with respect for scientists and researchers - can science be so certain about one thing, it overlooks others?

INGRASSIA: Yes. But the good news is that there are always scientists out there, always pioneers out there who are searching for answers and who say maybe what we think we know is not the whole truth. We know so much more than we used to know, but there's still so much more to learn. For example, why did my nephew get his first cancer at age 2, and my brother didn't get his first cancer until age 46, and they're different cancers?

SIMON: You know I've got to ask this. How are you?

INGRASSIA: I am at peace. I am sad to have lost my family. I am very fortunate. I tested negative for the mutation. You know, there's a 50/50 chance...

SIMON: Yeah.

INGRASSIA: ...That you will inherit the mutation. I tested negative, which means that I can't pass it on to my children, which means that it can't be passed on to my grandchildren. I have two children and six grandchildren. And, you know, Scott, there has been a lot of pain in my life, but I know that in a lot of people's lives, there's a lot of pain. And I think my brother and I tried to focus on also how blessed we were, having these wonderful experiences and careers working for these great news organizations, having wonderful families. You know, even with all the cancers, I think we can look back and say, you know, life in many ways has been good to us. Thank you. Thank you.

SIMON: Lawrence Ingrassia - his new book, "A Fatal Inheritance: How A Family Misfortune Revealed a Deadly Medical Mystery." Larry, thanks so much for joining us.

INGRASSIA: Scott, I really hope that this will help families like mine. This is a love story to my family, but it is a love story to all those families.

(SOUNDBITE OF MUSIC) Transcript provided by NPR, Copyright NPR.

NPR transcripts are created on a rush deadline by an NPR contractor. This text may not be in its final form and may be updated or revised in the future. Accuracy and availability may vary. The authoritative record of NPR’s programming is the audio record.

Scott Simon is one of America's most admired writers and broadcasters. He is the host of Weekend Edition Saturday and is one of the hosts of NPR's morning news podcast Up First. He has reported from all fifty states, five continents, and ten wars, from El Salvador to Sarajevo to Afghanistan and Iraq. His books have chronicled character and characters, in war and peace, sports and art, tragedy and comedy.