The Nobel Laureate Otto Warburg was regarded as one of the most significant biochemists of the 20th century, whose exhaustive research led to an understanding of cancer that remains significant to this day. Warburg was also one of the most despised figures in his homeland of Nazi Germany. As a Jewish homosexual, Warburg was a poster boy for all the Third Reich detested to the point of annihilation. Yet Adolf Hitler, who dreaded cancer, protected Warburg in the hope that he could cure the disease.

BOOKMARK

Title: Ravenous: Otto Warburg, the Nazis, and the Search for the Cancer-Diet Connection

Author: Sam Apple

Publisher: Liveright Publishing Corporation

Publication Date: May 2021

Price: $27.95, hardcover, 416 pages

A new book by Sam Apple, Ravenous: Otto -Warburg, the Nazis, and the Search for the Cancer-Diet Connection, brings Otto Warburg to life, in painstaking detail that will intrigue lovers of science, history, and high drama. Mr. Apple, who has written for notable publications such as The New York Times Magazine, The Atlantic, and TheNew Yorker, is also on the faculty of the Johns Hopkins science writing program, which becomes clear as he deftly delivers high-concept science into a lay-public gem.

A Complicated Genius

Born in Freiburg, Germany, in 1863, Warburg was a physiologist, medical doctor, and sole recipient of the Noble Prize in Physiology or Medicine in 1931; he was nominated for the award 47 times during his career. During World War I, Warburg served as an officer in the cavalry on the front, where he won the Iron Cross for valor. As the outcome of the war was inevitable, fearing the world would lose a great mind, Albert Einstein beseeched Warburg to leave the army and return to academic research.

After winning the Nobel Prize, Warburg was named Director of the Kaiser Wilhelm Institute for Cell Physiology. It was there he would ramp up his research in the metabolism of tumors and cellular respiration, particularly cancer cells. Although Ravenous is a rich read on many levels, the sections on his groundbreaking cancer research will be the most interesting to readers of The ASCO Post, and it is in those sections where Mr. Apple shines, as his passion and belief in Warburg’s sometimes exotic scientific theories are palpable.

Seminal Finding

Mr. Apple points out that the Nazis interest in Otto Warburg was rooted in established science, albeit, of the time. “Warburg created several tools to measure the metabolism of cells. When he used those tools to study cancer cells, he was amazed at what he found. The cancer cells were not eating like other cells. They were swallowing up huge portions of glucose—as much as 10 times that of healthy cells in the same tissues. The cancer cells were eating like shipwrecked sailors. They were ravenous,” writes Mr. Apple, alluding to the title of his fine book.

What Warburg also found was that cancer cells were using fermentation as the engine to create energy via ATP production, instead of oxidative phosphorylation, as normal cells do. This finding would lead to the famous Warburg hypothesis, which postulates that the driver of tumorigenesis is an insufficient cellular respiration caused by insult to mitochondria. Warburg would state: “Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause. Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.”

Trip to the United States

Mr. Apple describes the end of World War II in vivid, page-turning detail. Because Warburg was in an area occupied by the Soviets, who were enamored of his scientific genius, they tried to conscript him into their ranks and make him a Soviet scientist. They confiscated Warburg’s scientific equipment and many of his manuscripts, but he used guile and street smarts gained from his service in World War I to escape.

In 1947, Robert Emerson, a prominent American botanist, invited Warburg to spend 6 months in Urbana at the University of Illinois. For the scientific community, Warburg’s arrival was a major happening. In September, TheNew York Times ran an article about Warburg’s efforts to cure cancer by blocking the enzymes of fermentation. His time in the United States was lively, controversial, and filled with scientific backstabbing, all of which makes for a great read.

Return to the Fatherland

Warburg would return to Germany and remain there, heading the Kaiser Wilhelm Institute for Cell Physiology. He worked in his lab and published in major scientific journals. However, with the advent of the somatic mutation theory of cancer, acceptance of his metabolic theory waned and eventually withered on the academic vine. As molecular biologists studying cancer turned their attention to DNA and cancer-causing genes, Warburg’s research in how cells extract energy from food and use fermentation as the energy driver seemed not only outdated but backward. A 1972 article in the German magazine Der Spiegel claimed that Warburg’s research had “unilaterally” sent cancer research in the wrong direction. The attacks were unfounded, but as Warburg often quoted an aphorism attributed to Max Planck: “Science advances one funeral at a time.”

Warburg died of a pulmonary embolism in 1970. Today, his metabolic theory of cancer is gaining new interest. He did not live long enough to see convincing evidence linking sugar to the strange metabolism of cancer, and all that it means in terms of future research. He was a strange and complicated genius, whose work is still being investigated. Mr. Apple has written a tour de force, which, given its cancer-driven narrative, is highly recommended for readers of The ASCO Post.