InterviewWarburg Effect: Cancer cells fuel growth through glucose

Why the Nazis allowed a Jewish cancer scientist to remain in Berlin during WWII

Sam Apple’s new book ‘Ravenous’ tackles the fascinating scientific nexus between cellular metabolism and oncogenes, warning of a link between excessive sugar consumption and cancer

Renee Ghert-Zand is the health reporter and a feature writer for The Times of Israel.

  • Otto Warburg in his laboratory at the Kaiser Wilhelm Institutes. (The German Federal Archives)
    Otto Warburg in his laboratory at the Kaiser Wilhelm Institutes. (The German Federal Archives)
  • Otto Warburg at work (Archive of Frederic Burk)
    Otto Warburg at work (Archive of Frederic Burk)
  • Otto Warburg (second from right) with scientists at the University of Illinois at Urbana. (University of Illinois Archives)
    Otto Warburg (second from right) with scientists at the University of Illinois at Urbana. (University of Illinois Archives)

In June 1941, just hours before Germany’s invasion of the Soviet Union, renowned biochemist Otto Warburg was summoned to Nazi headquarters in Berlin.

As other great Jewish scientists such as Albert Einstein, Fritz Haber and Lise Meitner fled the country in the 1930s due to persecution, Nobel laureate Warburg defiantly stayed put as director of the Kaiser Wilhelm Institute for Cell Physiology in Berlin.

Overly assured and notoriously arrogant, the half-Jewish and apparently gay Warburg withstood all intimidation from Nazi officials. The way he saw it, he and his genius predated the Nazis, so he would not be bullied or succumb to threats.

However, Warburg feared the compulsory June 1941 invitation to Nazi headquarters signaled that his luck had run out. Fortunately for Warburg, Hitler and the Nazi leadership were more concerned about the exponential increase in cancer cases among the Aryan master race than about Warburg’s mischling (part-Jewish) status.

Regardless of whether Hitler himself was personally aware of Warburg’s research, there were enough people in Hitler’s inner circle who believed that Warburg’s expert knowledge of the metabolism of cancer cells could offer hope for a cure to the disease. Warburg would have to move his lab to a different location, but he could stay.

Of the many Jewish scientists and scientists of Jewish descent who worked at the world-famous Kaiser Wilhelm Institute (now the Max Plank Institutes), Warburg was the only one to remain. The rest either became refugees or victims of the Holocaust.

‘Ravenous: Otto Warburg, the Nazis, and the Search for the Cancer-Diet Connection’ (Liveright)

The life and work of the brilliant and idiosyncratic Warburg serve as the frame for author Sam Apple’s fascinating new book about the link between diet and cancer. Ravenous: Otto Warburg, the Nazis, and the Search for the Cancer-Diet Connection” was published in May 2021, and has received positive reviews from both cancer researchers and general readers interested in how the way we eat in Western societies (specifically the inordinate amounts of sugar we consume) make us vulnerable to cancer.

Although the book has biographical and historical elements, “Ravenous” is first and foremost about scientific research on the molecular and cellular level.

“One of my concerns was that there is a lot of science in the book, particularly at the end,” Apple told The Times of Israel in a recent Zoom interview from his home in the Philadelphia area.

“For some people it’s too much, but I’ve been pleasantly surprised that a lot of people without science backgrounds have told me that despite not necessarily understanding every facet of it, they were able to follow the broader logic,” he said.

Sam Apple (Mark Tassoni)

The book is the result of five years of work expanding on a 2016 New York Times Magazine article by Apple on how today’s researchers are again recognizing the importance of Warburg’s findings on cancer cell metabolism — specifically the Warburg Effect, which theorizes that cancer cells fuel their growth by swallowing up enormous amounts of glucose, or blood sugar, and breaking it down without oxygen through fermentation.

As genetics and molecular biology took off in the 1950s and 1960s, the pendulum swung completely away from metabolism to the point that mention of Warburg — arguably the greatest biochemist of the first half of the 20th century — disappeared from scientific papers and medical textbooks. It was only in the new millennium that scientists began to realize that fixing or shutting off genetic mutations alone would not cure cancer. Rather, the interplay between genetics and metabolism was likely the key.

A professor of writing at Johns Hopkins University in Baltimore, Apple, 45, has focused on science reporting in the last decade. As he delved into learning more about obesity and Type 2 diabetes (and related insulin resistance), Apple was surprised to learn that there was evidence linking cancer to these conditions.

“I understood heart disease was part of these conditions, but I really did not think cancer was related. I grew more curious,” Apple said.

As Apple read more, he came across mention of Warburg in an article. It was just one sentence stating that in 1923 a famous German scientist discovered that cancer cells take up a lot of glucose and ferment it.

Otto Warburg at work (Archive of Frederic Burk)

Apple performed an internet search on Warburg and was fascinated to learn about his background, including the fact that he was a member of the illustrious Warburg banking family and the son of noted German physicist Emil Warburg. (Otto Warburg’s mother was not Jewish and he did not identify as Jewish.)

“I’ve written about the Holocaust and Jewish themes many different times over the years, including my book ‘Schlepping Through The Alps.’ So once I saw Warburg’s story, it was sort of a marriage of the two things I was interested in — the Jewish historical side and the captivating science,” Apple said.

As intrigued as Apple was by Warburg’s life and difficult personality — he was known to never admit being wrong but was quick to point out others’ shortcomings — the author wasn’t interested in writing Warburg’s biography.

“It’s really a book about cancer and diet, with Warburg as its main character and with Hitler and German history brought into it, as well,” Apple said.

In Apple’s opinion, it is unfortunate that metabolism science as it relates to cancer was largely ignored from the 1960s to the late 1990s.

“I do think that set cancer science back. It would have made a big difference if people had thought about Warburg’s fundamental discovery and the importance of metabolism,” Apple said.

He finds it amazing that even as physicians used PET scans — which look at where the body is taking up more glucose — as a diagnostic test for cancer, the focus for decades was still almost exclusively on genetics.

The neglect shown to Warburg’s findings was partly due to the excitement about molecular biology and the theory that cancer could be treated by turning off genetic mutations. But Apple posits that it was also due to Warburg’s outrageous behavior and belittling of colleagues, as well as his having remained in Nazi Germany, carrying on as though nothing had changed.

Apple mentions in “Ravenous” that while interviewing pioneering cancer researcher Robert Weinberg, the Massachusetts Institute of Technology scientist confessed to “harboring very negative feelings about Warburg because of his Nazi affiliation.”

“I make it clear in the book that Warburg was not sympathetic to the Nazi cause,” Apple said. “But it is certainly understandable that people were skeptical of him given that he stayed.”

He added that Weinberg, a Jew whose parents fled Nazi Germany in 1938, wasn’t alone in his dislike for Warburg.

The author thinks that on a simple level, Warburg grasped that people were angry at him, whether because he remained in Germany or for his superior demeanor. However, as a narcissist, he wasn’t capable of fully sympathizing with others’ points of view.

Otto Warburg (second from right) with scientists at the University of Illinois at Urbana. (University of Illinois Archives)

“He saw any dislike of him as unfair treatment. He couldn’t comprehend that he had ever done anything wrong. His crime was not being able to think about anyone other than himself,” Apple said.

Warburg’s theories and 21st-century cancer research come together in the final section of “Ravenous,” in which Apple explains how today’s scientists have discovered that mutations in oncogenes (genes with the potential to cause cancer) are the ones that affect metabolism.

His crime was not being able to think about anyone other than himself

“I could have just told the story of the cancer cell and understanding oncogenes and metabolic enzymes, but I also wanted to go one step further and see if we could connect that to whole-body metabolism and the way we eat,” Apple said.

From left: Drs. Otto Warburg, Bernardo Houssay and NIH Director Rollo E. Dyer at the National Institutes of Health. (NIH History Office, Public domain, via Wikimedia Commons)

“For me, the real breakthrough was understanding the relationship between diet, insulin and the mechanics of the cancer cell,” he said.

“Ravenous” is not the only book that warns of the unique harmfulness of sugar and how it drives insulin resistance, which has turned out to be an important risk factor for cancer.

Apple said that with “Ravenous,” his intention is to be among those sounding the alarm about the dangers of excessive sugar consumption.

“I hope people enjoy the book, but I hope the sugar part scares them a bit. It certainly scares me,” said Apple.

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