Book Review: Ravenous by Sam Apple

Dr. James Odell, OMD, ND, L.Ac.

In Ravenous, Sam Apple tells the incredible story of how Otto Warburg, a Nobel Prize-winning biochemist, and a homosexual of Jewish descent, survived the Third Reich in a posh Berlin suburb, and how his theories of metabolic cancer cells may yet hold the key to finding a cure for this epidemic disease of our time. Warburg was commonly considered in his day as one of the most brilliant and influential biochemists of the twentieth century, a man whose research was integral to humanity’s understanding of cancer. However, he was among the most despised figures in Nazi Germany. As a Jewish homosexual living openly with his male partner, Warburg represented all that the Third Reich detested. Yet Hitler and his top advisors greatly feared cancer, and protected Warburg in the hope that he could cure it.

While most Jewish scientists fled Germany in the troubling years leading up to World War II, Warburg remained in Berlin, working under the watchful eye of the Third Reich. While Nazis rounded up and systematically murdered or imprisoned millions of Jews political dissidents, Warburg awoke each morning in the affluence of a beautiful home and rode horses with his partner, Jacob Heiss, before delving into his research at the Kaiser Wilhelm Society.

Apple shows that Hitler and other Nazi leaders were deeply concerned by increasing cancer rates across Europe, viewing cancer as an existential threat akin to Judaism or homosexuality. Ironically, they viewed Warburg as Germany’s best chance of survival. Setting Warburg’s work against an absorbing history of cancer science, Apple journals him as he arrives at his central belief that cancer is a problem of metabolism.

Warburg’s central observation of cancer metabolism later became referred to as the ‘Warburg Effect’. He discovered that lactate production from glycolysis did not depend on the presence of oxygen. That had not been expected, since according to Pasteur, the presence of oxygen should have suppressed glycolysis. The fact that there appeared to be no direct relationship between respiration and glycolysis led to the conclusion that in cancer cells, glycolysis was a reaction which could produce energy, independent of respiration (oxygen consumption). In other experiments with varying glucose and bicarbonate concentrations, it was shown that there was no generalizable difference in oxygen consumption between the tumor and the respective normal epithelial tissue. Warburg hypothesized that there was a defect in the relationship between glycolysis and respiration. Even though this observation was corroborated with other tumors by several contemporary scientists, the observation that oxygen could not suppress glycolysis prompted him to propose that a damage in respiration leads to carcinogenesis.

Warburg further demonstrated that cancers frequently rely less on mitochondria and obtain as much as 50% of their ATP by metabolizing glucose directly to lactic acid, even in the presence of oxygen. This came to be a highly controversial issue climaxing in his famous papers in Science in 1956.

Though Warburg’s metabolic approach to cancer was considered groundbreaking, his work was soon eclipsed in the early postwar era, after the discovery of the structure of DNA set off a search for the genetic origins of cancer. He was awarded the Nobel Prize in Physiology in 1931 for his discovery of the respiratory enzyme cytochrome c oxidase (CcO), which resides at the inner mitochondrial membrane.

Defects in mitochondrial oxidative phosphorylation complexes, altered bioenergetics and a metabolic shift to fermentation are often seen in cancers. Warburg’s research has now been proven to show that a defect in a mitochondrial electron transport component, the cytochrome c oxidase, leads to increased glycolysis and carcinogenesis

Remarkably, Warburg’s theory has undergone a resurgence in our own time, as scientists have begun to investigate the dangers of sugar and the link between obesity and cancer, finding that the way we eat can influence how cancer cells take up nutrients and grow.

Warburg was a role model for meticulous research, contributing so much towards our knowledge of how best to diagnose and treat cancer. Apple demonstrates how Warburg’s midcentury work may well hold the secret to why cancer became so common in the modern world and how we can reverse the trend. A tale of scientific discovery, personal peril, and the race to end a disastrous disease, Ravenous would be the stuff of the most inventive fiction were it not, in fact, true.

In short, this is a bona fide page-turner.

Sam Apple has written for the New York Times Magazine, Wired, The Atlantic, MIT Technology Review, and The New Yorker. He is on the faculty of MA in Science Writing and MA in Writing programs at John Hopkins.

For a biographic summary of Otto Warburg visit: