A Fatal Inheritance

December 1, 2023

Ingrassia (Billion Dollar Brand Club), a former business and economics editor at the New York Times, turns to his own family story after losing several relatives to cancer. Interweaving his personal narrative with the history of cancer research, he offers a riveting medical memoir. With a 75K-copy first printing. Prepub Alert.

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April 1, 2024
A journalist tracks cancer through his family history. "[My mother] was one of 318,500 Americans who died of cancer in 1968," writes Ingrassia, former deputy managing editor of the New York Times and author of Billion Dollar Brand Club. "It was tragic, but what was there to say?" He adds that there is more to say, for cancer would befall the family again. His mother's death coincided with an upsurge in cancer research, as well as its politicization, as scientists urged Richard Nixon to declare war on it, noting that for every $410 spent on national defense only $0.89 went to studying cancer. Scientists noted that there was a hereditary aspect to cancer, and though not every sibling might fall ill, many certainly did. Some suspected environmental causes; many researchers attributed cancer to a mysterious virus. One particularly difficult illness to figure out, given that cancer is generally rare in children, was pediatric retinoblastoma. When an explanation based on two gene mutations was proposed, "it was greeted with some skepticism, because it was based on a mathematical calculation rather than scientific evidence gathered in a lab experiment." Even so, the implication of genes and mutation eventually carried the day in numerous studies that gained force when genes were sequenced, allowing a clearer understanding of hereditary cancers--which turn out, though, not to be statistically hugely significant, for all the pain they have brought to many families. As one Nobel Prize-winning scientist observed, "Every single cancer is different when you look at it on a genetic level. It's not one disease, it's many different diseases." Still, writes Ingrassia in this memorable chronicle, the distribution of causation falls mostly on environmental factors, with viruses having a comparatively minor role. An impressive, deeply researched contribution to popular studies of epidemiology and oncology.

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April 15, 2024
Mingling medical research, memories, and melancholy, journalist Ingrassia shares the tragic stories of families cursed with and devastated by cancer. In his own family, his mother, brother, two sisters, and a nephew died (most at a young age) from malignancies. Ingrassia recounts the dueling fortitude and fatalism that grips those struck by these hereditary cancer syndromes. He reports on the medical detective work conducted by physicians and scientists to track down the cause. In the hereditary cancer profiled here, Li-Fraumeni syndrome, the problem is the p53 gene, a gene responsible for a protein that prevents damaged cells from becoming cancerous. But the gene sometimes mutates and loses its ability to control altered cells that then become malignant. Sadly, the mutated p53 gene can be passed on to offspring. While genetic testing is available, no curative treatment for the mutation presently exists. Frequent and extensive screenings for the detection of possible tumors are recommended so early intervention can be initiated. This is an emotionally charged narrative about genetic proneness to cancer, the promise of scientific discovery, hope, loss, grief, and, especially, familial love.

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July 8, 2024
The discovery of a fatal inheritable cancer is recapped in this arresting account from journalist Ingrassia (Billion Dollar Brand Club), whose family suffers from the disease. Through interviews with other affected families, Ingrassia emphasizes the extreme devastation wrought by Li-Fraumeni syndrome, which has a 50% chance of being passed down from parent to child (“These families... are extremely fatalistic, particularly the older people who have so many relatives,” explains one doctor; Ingrassia notes that many gene carriers die as children, compounding the families’ trauma). He pairs these harrowing accounts with a riveting scientific detective story. Through the 1960s, scientists believed all cancers were viral or environmental, but in 1969, two cancer researchers, Frederick Li and Joseph Fraumeni, compiled medical charts and death certificates of children diagnosed with a rare cancer, rhabdomyosarcoma, and were shocked to find many were related. Li and Fraumeni tracked the children’s families for 20 years, over which time 40 of the 57 family members were diagnosed with 52 different cancers. In 1990, the gene mutation that causes LFS was identified, kicking off a hunt for more genetically caused cancers; however, researchers have yet to develop successful treatments for LFS. Ingrassia’s account is at its most wrenching when he recalls his own loss—all three of his siblings have succumbed to the disease. It’s an evocative look at a pivotal episode in the history of cancer research. (May)Correction: A previous version of this review incorrectly stated that the gene mutation that causes LFS was identified in 1979.