"Ravenous" - A Book Review

Author Sam Apple received an undergraduate degree from the University of Michigan and studied writing at Columbia University. He has written articles that have appeared in such diverse publications as The Los Angeles Times, The Financial Times, and ESPN The Magazine. In 2021 he wrote "Ravenous: Otto Warburg, the Nazis, and the Search for the Cancer-Diet Connection." It is a compelling read and a real page-turner; a non-fiction book that reads like fiction. Even if you are not normally a fan of science writing, you probably have had a friend or family member affected by cancer. If you value your health and you value learning, the information presented in this book should be of interest to you.

"Ravenous" covers the history of cancer research and experimentation in four parts, starting with the late 19th century and working up to the present. A central figure of the book is Otto Warburg, considered by many to be one of the preeminent German scientists of the first half of the 20th century. He was a contemporary of Albert Einstein, and in many ways Warburg was just as influential in his field of physiology as Einstein was in physics. By most accounts Warburg was stubborn, arrogant, and insufferable to be around; he expected those who worked in his lab to have his same drive and to keep the same round-the-clock schedule as he did. However flawed he may have been in dealing with others, this insatiable intellectual curiosity led to some amazing discoveries, as well as the Nobel Prize for Physiology or Medicine in 1931. Warburg's decision to study cancer was largely due to two factors: rising rates of cancer diagnoses in the western world (and Germany in particular), and also the curious case of Crown Prince Friedrich, heir to the throne of Germany. Friedrich was beloved by the German people, yet was diagnosed with and succumbed to cancer after merely four months on the throne. As an interesting footnote, history may have changed significantly if not for this unfortunate occurrence. The Crown Prince was said to detest war, favored democratic reforms, and was quite sympathetic to German Jews. Had he survived, Kaiser Wilhelm would not have come to power, World War I might not have occurred, and the world could have been spared the evil atrocities of Adolf Hitler and World War II.

Warburg's key discovery was that cancer cells, "Produce energy not through the usual citric acid cycle and oxidative phosphorylation in the mitochondria as observed in normal cells, but through a less efficient process of 'aerobic glycolysis' consisting of a high level of glucose uptake and glycolysis followed by lactic acid fermentation taking place in the cytosol, not in the mitochondria, even in the presence of abundant oxygen." This was a startling revelation, and it gave credence to the idea that cancer was largely a metabolic disease, not a genetic condition. The 'Warburg Effect' went a long way toward explaining not only how cancer cells multiply so rapidly in many cases, but it also shed light on why cancer rates started skyrocketing in the western world in the late 19th and early 20th century: increased sugar consumption. What was different in the more affluent western world, compared to most of the developing world, was that sugar was much more available and present in the foods people ate. Where it was more expensive and harder to produce, cancer rates remained relatively low. Once sugar became easier to produce, cancer rates in those areas climbed. Unfortunately, with the rise of Hitler and the Nazis, Warburg's progress stalled and his work began to suffer. He was constantly harassed for his Jewish heritage and rumors circulated about his homosexuality, so he found it extremely difficult to keep a staff together and have enough funding to continue his research. Yet he stubbornly refused to leave Germany as many other prominent scientists did during this time, and many of his colleagues harbored resentment toward him and his theories. Some of this was due to jealousy and Warburg's notoriously abrasive personality (he rarely admitted to being wrong), but he was also unfairly branded as a Nazi sympathizer. Unfortunately, much of Warburg's work was largely forgotten in the scientific community once James Watson and Francis Crick discovered DNA in 1953. At that point, cancer research shifted toward a genetic mindset rather than a metabolic inclination, and that was where the focus stayed for most of the next half century.

In the last twenty years or so, Otto Warburg's reputation has been rejuvenated as we have gained a greater understanding of the links between cancer and diabetes, the dangers of sugar and how diet can cause genetic predispositions to be expressed, and the role of insulin. Diabetes can either be type 1 (insulin dependent) or type 2 (insulin resistant); insulin is the hormone that is secreted by the pancreas to help the cells absorb the nutrients from the food we consume. If you consume a large percentage of your calories from carbohydrates (especially sugar), more insulin needs to be secreted in order to help the cells absorb nutrients. At a certain point one becomes insulin resistant, thus leading to type 2 diabetes. According to the author, "Since 1960 the diabetes rate in the United States has increased by 800 percent, and half of American adults are now estimated to have either diabetes or prediabetes." Further, a consensus report by the American Diabetes Association and the American Cancer Society states that, "Epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer." Fortunately, many younger scientists have taken up the mantle of Warburg's work and continue to explore the metabolic aspect of the disease, rather than simply tow the establishment line about it being simply genetic or environmental.

This book has many interesting components. There is certainly a historical and political angle that covers world events, but it also discloses the fun fact that Hitler was a sugar addict and that most of his teeth had fallen out near the end of his life. I also enjoyed the profile of Warburg's courage in standing up to the Nazis, and the price he paid for his bravery. Apple gives excellent examples of the modern impact of Warburg's work and how cancer treatments have changed over the years, but also what the future might hold. In this book we also learn that the first chemotherapy drugs originated from the emerging German chemical dye industry of the late 19th century. Paul Ehrlich is mentioned as a pioneer in the development of so-called "magic bullets" designed to target tumors while sparing healthy tissue. Unfortunately, as we know, this did not happen; as the author states, "Firing a bullet at cancer was like turning a gun on yourself."

"Ravenous" is a compelling book that I would recommend to anyone with an interest in history, cancer research, or science in general. Apple does a wonderful job of documenting the timeline of research, its origins, and where we may head in the future. His praise and his criticisms of Otto Warburg are accurate; he was right about many things, wrong about others, arrogant, but also brilliant. The author writes extremely well, as you might expect from someone who is on the MA in Science Writing at Johns Hopkins, and his prose makes you want to turn the page and see what's going to happen next. Pick up a copy and experience it for yourself.