When Regina Ingrassia died at 42, leaving four children, her death seemed cataclysmic but random. “She was one of 318,500 Americans who died of cancer in 1968,” Lawrence Ingrassia, her second-oldest child, writes. “It was tragic, but what was there to say?”
Part memoir, part medical mystery, Ingrassia’s deeply reported book interweaves two narratives. One is the poignant and distressing story of his family, and others, who were repeatedly menaced by something they knew nothing about. The other is the often stirring account of scientists who worked tirelessly to unravel the mystery. Ultimately, researchers identified an inherited cancer syndrome and, eventually, the culprit behind it.
“A Fatal Inheritance” is not a beach book; reading about the agonized families can be painful and frustrating, given there still is no cure for the disorder. But readers will be rewarded with a detailed look at the high — and all-too-human — stakes of cancer research. And the anecdotes about the scientists, by turns inspirational and competitive, leaven the stories of heartbreak.
Ingrassia, a former high-ranking editor at the New York Times, the Wall Street Journal and the Los Angeles Times, wisely sets his narratives within the broader framework of cancer research, with its various fads and preoccupations. At the time of his mother’s death, few scientists were focusing on an inherited susceptibility to cancer; viruses were viewed as much more likely to cause the disease. But at the National Cancer Institute, two young epidemiologists — Frederick Pei Li and Joseph F. Fraumeni Jr. — were beginning what would be their lives’ work: studying the fatal predisposition that seemed to run in some families.
Piquing their interest was an unusual case that Li heard about at a dinner party: A young father, named Ned Kilius, was undergoing treatment for leukemia in Baltimore at the same time his 10-month-old son, Darrel, was being seen for a rare soft-tissue cancer in his arm. The patients’ doctors did not see a connection. But Li and Fraumeni were intrigued, constructing a detailed medical history of the Kilius clan that showed an unusually high rate of malignancies. The work was central to their seminal 1969 paper, which suggested the discovery of a previously unknown inherited cancer syndrome. The paper got little attention. But in subsequent years, Li and Fraumeni found additional cancer-prone families, and the disorder came to be known as Li-Fraumeni syndrome.
In 1990, scientists discovered the cause of the cancer syndrome — a mutation in a gene called p53 that normally suppresses tumors but, if defective, can allow cancer to grow uncontrollably. If a parent has the mutation, a child has a 50 percent chance of inheriting it, drastically raising the risk of cancer.
Only about 5 to 10 percent of cancers are caused by inherited cancer disorders, Ingrassia writes, and Li-Fraumeni syndrome is among the rarest. But research into the condition has provided important insights into cancer mechanics in general.
While lucidly describing the science involved, Ingrassia keeps the focus on the beating heart of the book — the patients, many of whom were stricken at a young age, often more than once. Darrel Kilius, who as a baby had survived the soft-tissue cancer by having part of his right arm removed, was battered by tumors in his 20s and died at 29.
The Ingrassia family fared no better.
In the 1980s, Lawrence writes, his younger sisters died at 24 and 32. His nephew Charlie was diagnosed at 2 with the first of three different cancers. In 1997, Charlie’s father — Paul Ingrassia, a Pulitzer Prize-winning journalist for the Wall Street Journal and Dow Jones Newswires — developed early-stage lung cancer at 46. (I knew Paul, as we both worked at the Journal, but was never aware of his health situation.)
Sometimes, the brothers wondered why their family was so unlucky. Had their father, a research chemist, inadvertently carried toxic chemicals home on his clothes? They were unaware of Li-Fraumeni syndrome — as were many doctors — and genetic testing outside of studies was years away.
But in late 2014, the mystery was finally resolved. Paul underwent genetic testing and was positive for the p53 mutation, a huge blow. His brother, tested later, was negative, a big relief. When Lawrence emailed his brother about the fortuitous result, Paul quickly responded, “Great news!!!”
There are other moments of grace and courage. In 2019, while Paul battled pancreatic cancer, his son Charlie fought bone cancer that required the amputation of his leg. A week before Charlie died at 39, he renewed his Chicago Cubs baseball tickets. A few months later, 69-year-old Paul called friends from the ICU to say goodbye.
Today, Ingrassia writes, there are a few glimmers of hope for people with the disorder. Intensive screening is detecting some cancers early enough to save lives. And the gene-editing technology CRISPR might someday be a useful tool for treating the condition.
But that is far down the road. When Paul was diagnosed with pancreatic cancer, he received harsh chemotherapy, not a high-tech game changer.
Still, Paul was not one to complain, his brother writes. Accepting a prestigious journalism award for lifetime achievement a few years before he died, Paul deadpanned, “I often think my biggest lifetime achievement is simply having a lifetime.”
Laurie McGinley is a former health reporter and editor at The Washington Post and the Wall Street Journal.
A Fatal Inheritance
How a Family Misfortune Revealed a Deadly Medical Mystery
By Lawrence Ingrassia
Henry Holt. 320 pp. $29.99
A note to our readers
We are a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for us to earn fees by linking to Amazon.com and affiliated sites.
