Author Talks: How decades of cancer research shed light on the power of genetics

In this edition of Author Talks, McKinsey Global Publishing’s Querida Anderson chats with Lawrence Ingrassia about his book A Fatal Inheritance: How a Family Misfortune Revealed a Deadly Medical Mystery (Henry Holt and Co./Macmillan Publishers, May 2024). Ingrassia details his family’s battle with numerous cancers, spotlights the pioneers who worked tirelessly to solve the puzzle of genetic mutations, and explores the ongoing advancement in cancer research and development. An edited version of the conversation follows, and you can also watch the full video at the end of this page.

Why did you write a book about Li-Fraumeni syndrome and your family’s experience with it?

A Fatal Inheritance is a memoir and medical detective story about my family and families like mine who question seemingly unrelated cancer diagnoses and about the doctors who solved the medical mystery behind those cancers. The writing process helped me expand my understanding of cancer and cancer treatment improvement.

Initially, I didn’t plan to write a book. I wanted to learn more about Li-Fraumeni syndrome, the cancer condition that robbed me of my family. My mother died of breast cancer at 42, and my youngest sister died of abdominal cancer at 24. Additionally, my other sister died of lung cancer at 32, my brother died of cancer at 69, and his son was diagnosed with his first cancer when he was only two years old.

I knew a genetic mutation caused Li-Fraumeni syndrome, but I wanted to know more. I decided to research online, and what I saw intrigued me. As of 2011, approximately 500 families in the United States have Li-Fraumeni syndrome. Children and young adults often get cancer with the syndrome, which is unusual.

During my research, I discovered Dr. Joseph Fraumeni, who began studying cancer-prone families in the late 1960s with Dr. Frederick Li. Dr. Fraumeni is still alive, while Dr. Li died in 2015. So I called Dr. Fraumeni to learn more about the syndrome. Talking to Dr. Fraumeni intrigued me; he spoke about how he stumbled across a family in the late 1960s that included a young father with leukemia and his baby son, who had a soft cancer tissue in his arm. It was unusual.

When the doctors investigated the family’s history, what they found was even more bizarre: various types of cancer had riddled the family for generations. Therefore, the doctors continued to study the family members and wrote a paper detailing how they weren’t sure what was occurring but considered that the cancer could be hereditary. This was at a time when little was known about cancer and much less was known about cancer genetics. The experts didn’t believe that cancer could be hereditary.

Dr. Fraumeni and Dr. Li began their journey to find answers. Persistent, undeterred, and curious, they kept searching.

After that conversation, I knew there was something intriguing for me to write about, and I wanted to continue learning more. Then my journalistic instincts kicked in.

How did you emotionally prepare to write about a deadly disease that affected your family?

Writing about family and painful moments that involve your family can be difficult. Many people feel their most intense emotions during difficult times. I felt those emotions when I experienced my mom’s, sisters’, and brother’s deaths.

Writing about my family was a way for me to get to know them better and feel closer to them; that was one of the reasons I began this journey. I looked through old photographs, which brought back many memories, and talked to relatives who knew my parents better than I had ever known them.

Then, with my wife’s help, I reconnected with my youngest sister’s best friend, Angela, who was at my sister’s side from the beginning of her diagnosis until she died six months later. Angela helped me understand my sister’s fears, hopes, and what she thought she would miss out on. Of course, hearing those things brought me to tears, but it felt good to learn more about her and her thought process.

My other sister, Gina, died at 32. She started a diary when she found out about her cancer diagnosis and wrote until she couldn’t write anymore. After her death, her husband shared it with me. It was painful to read, but it made me feel close to her. She wrote about willpower and believed that if she had enough of it, she could beat cancer. While reading that, all I could think was that it was a genetic mutation and that she could do nothing.

Learning more about my family was cathartic. It meant so much to me and was my life’s most rewarding writing experience.

Can you share more about the decades’ worth of cancer research you traced?

When I began writing, I knew little about cancer science and scientific research; I had to talk to numerous people and read academic papers, which contained a lot of jargon.

Through conversations, you can gain valuable insights and a better understanding of the historical context of cancer research. Dr. Fraumeni played a significant role in helping me grasp the initial landscape of cancer research when he and Dr. Li embarked on their study of genetically mutated families. At that time, [medical professionals] believed that viruses caused many cancers. Of course, that turned out to be inaccurate, but that thinking is why Dr. Fraumeni and Dr. Li’s research was initially dismissed.

I wanted to understand more about the evolution of cancer. It wasn’t a straight line. Instead, it was often a halted, meandering path. Over time, Dr. Fraumeni and Dr. Li followed that journey—those families—and learned more, but they weren’t the only ones.

A handful of other pioneers also hypothesized that genetics is more important to cancer than previously thought. So it wasn’t one person. All these things came together. It became a period of expanding knowledge, which led to an explosion in the scientific understanding of genetics. I focus on Dr. Fraumeni, Dr. Li, and their contributions, but other scientists were also expanding our understanding of cancer.

My aim was to narrate these stories through the lens of the scientists, who were propelled by a shared desire to alleviate the suffering of families affected by cancer.

What should those affected by cancer—and the cancer research and development community—take from A Fatal Inheritance?

I hope the families who read the book, particularly families that deal with many cancers, will know they are not alone. I want them to know there are ways to combat cancer; you may not be able to cure cancer, but there are ways to deal with it.

Also, I want people to know that if there is a lot of cancer in your family, it doesn’t mean that it’s hereditary; only 10 to 15 percent of cancers are. Most cancers are environmental, but I do encourage genetic testing. If cancer is hereditary in your family, you can get screened frequently. Frequent screenings catch cancers early; early detection is the best way to beat cancers.

My brother’s battle with cancer lasted until he was 69, which was relatively longer than it was for my mother and sisters. He received his first cancer diagnosis at 46, and he didn’t know that it was hereditary. After his diagnosis, he became very vigilant, constantly getting tested and screened. Although he had multiple cancers, he lived 22 years after his original cancer diagnosis.

I want drug companies and scientists to know they’ve made a difference. Cancer knowledge and treatment have increased dramatically in the past 50 years. Research has drastically improved breast, colon, and prostate cancer survival rates. Scientists like Dr. Fraumeni and Dr. Li are heroes who entered public service not to make money, but to help families.

How did you weave the science of cancer research with personal stories?

Cancer genetics and scientific research are complicated topics. As a journalist, I’ve learned that the best way to tell a story is through people and characters. I was fortunate to talk to interesting individuals, to whom I could tell my story and weave the science with the personal.

Dr. Fraumeni and Dr. Li are fascinating characters. Both are children of immigrants and were young “outsiders” when they began working at the NCI [National Cancer Institute]. They weren’t among the leading experts, but they had a passion and a goal to understand what was happening with cancer-prone families.

Second, I talked to surviving members of “Family A,” the original family Dr. Fraumeni and Dr. Li researched, starting in 1967. They didn’t have many memories, but they shared the few they had and talked through their grief. Additionally, they allowed me to access medical records from the NCI. I could trace the doctors’ steps with the records and ask questions such as, “What were they thinking when they came across this family? How did they track down medical records? How did they broaden their research and add more families?” I wanted to weave the science, the scientists, and the family together.

My mother died in 1968; therefore, I could tell that story in parallel. During that same period, Dr. Fraumeni and Dr. Li began their Family A research. Those parallels felt like an excellent way to weave together a narrative that explains complex ideas to readers in a meaningful way.

What surprised you the most while writing this book?

I didn’t realize how big of a story Li-Fraumeni syndrome was when it was identified in 1990. It wasn’t only massive in the scientific press, but it was also a national news story. It was on the front page of the New York Times and featured in the Wall Street Journal.

My brother and I both worked as editors at the Wall Street Journal. We didn’t write about science but were there during the Li-Fraumeni story. We overlooked the article and didn’t connect it to our family. Initially, we blamed our father’s cancer on his work; he was a research chemist. We believed he brought carcinogenic chemicals into our home via his clothing, but, of course, that was wrong.

Before our mother, there wasn’t a history of cancer in our family. How could that be if it’s hereditary? Doctors told me that it was because my mother likely had a de novo mutation, and she didn’t inherit it. Instead, she was probably born with that mutation in a particular gene. This mutation happens in about 5 to 10 percent of Li-Fraumeni patients; she was the first in our family to have the gene.

We never suspected this. No doctors ever told us, “All these various cancers in your family might be hereditary.”

The mutation that causes Li-Fraumeni syndrome occurs in a gene called p53. Doctors realized how important the gene was after they discovered it. It’s now the most studied single gene in the human body and is known as the “guardian of the genome,” because it usually functions as a cancer suppressor. Our cells constantly divide and mutate, and they can become cancerous. But our cancer suppressor protects us. When our p53 gene isn’t working correctly, the odds of getting cancer increase exponentially.

The last thing that surprised me was the race to find p53. Two teams discovered the mutation at the same time. One team received the credit, because they published their paper weeks before the other could. It was a fascinating backstory.

Was there a person, family, or moment that crystallized the story for you?

My brother and I were extraordinarily close—there were several reasons why our relationship was strong. Our parents and sisters died early on, so we just had each other and our individual families. We had so much in common; we worked together for over two decades. I always believed that if someone wrote a book about Li-Fraumeni syndrome, it would be him, because he and his son inherited the mutation.

I didn’t inherit it. I tested negative but often accompanied my brother to his doctor appointments. I stood by his side and held his hand, along with his wife, when he died. He lived with the mutation and never let it dominate him. Cancer wasn’t his life; he had a prosperous, successful career. He inspired me, and I felt close to him because we were the only survivors.

Are we doing enough to tackle cancer?

There was a feeling we could conquer and cure cancer when the “War on Cancer” was launched in the 1970s. It was a naive thought. Cancer is an incredibly complicated disease, but we’ve seen steady, incremental progress, thanks to scientists and drug companies.

I’ve noted that survival rates for some, but not all, cancers have increased, and we will see those continue to rise. There will not be an instant cure for cancer. Instead, we’ll see continued progress. The big question is how people will afford those drugs. Developing new drugs that target and kill cancer cells can cost hundreds of millions to billions of dollars.

There’s also a new technology, CRISPR, which edits genes. It can potentially repair hereditary mutations, and while it’s in the early stages of development, it holds immense promise. Any research that results from CRISPR will be costly, but it will pave the way for significant progress within the next five to ten years.

The overarching questions are, how will we, as a society, afford new drugs and who will have access to those drugs?

I commend scientists for the remarkable progress they’ve made. It’s incredible to think how little was known about cancer just 50–60 years ago. We’ve come a long way, and our increased understanding has significantly improved our ability to combat this disease and enhance survival rates.

Watch the full interview

Visit Author Talks to see the full series.

Learn more