Otto Warburg, Cancer Pioneer

This week, 83 years after Otto Warburg published his landmark paper on cancer, the New York Times has a major article on the revival of his idea that cancer cells can be starved to death (NYT, May 12, 2016).

Otto Warburg (1883 – 1970) was arguably the most brilliant and productive chemist of all time. Throughout his 50 years of research, he made major breakthroughs in intracellular respiration, photosynthesis and cancer.   Almost 100 years ago, in 1923, he showed that cancer cells are different from normal cells in that their primary source of energy comes from fermenting sugar without needing oxygen.  Today scientists are getting closer to curing cancer by following his brilliant breakthroughs. He was nominated for the Nobel Prize 47 times and won it in 1931.  He probably would have received another in 1944, but Hitler did not allow German scientists to accept Nobel prizes.

He trained many of the leading chemists of the 20th century in his laboratory.  He worked all the time, never married, never dated, and was never reported to have been seen socially with a woman. He appeared to be totally asexual, yet he was a very brave and athletic man. Throughout his incredibly productive lifetime, his only recreation appears to have been riding his horses; he was an accomplished competitive rider.

Warburg’s father was a noted professor of physics at the University of Berlin, and the family socialized with many of the world’s greatest physicists and chemists such as Albert Einstein, Max Planck, Emil Fischer and Walther Nernst.   As a student, Otto was the most brilliant of the brilliant. He received his Ph.D. at the very young age of 23 in 1906, studying chemistry at the University of Berlin under the great Emil Fischer, who won a 1902 Nobel Prize for making breakthroughs on what sugar is and how the body uses sugar for energy. He then studied under Ludolf von Krehl and received his M.D. from the University of Heidelberg in 1911.

In 1913, at the unusually young age of 30, he was appointed to head his own laboratory at the Kaiser Wilhelm Institute (later Max Planck Institute) in Berlin. He started making many important discoveries right away. However, when World War I broke out, he left the Institute to volunteer to be an officer in the elite Uhlans (cavalry). He served on the Russian front where he was wounded and received the Iron Cross for risking his life in battle. He probably would have become a general if Albert Einstein had not intervened. Einstein was a close personal friend of Warburg’s father, Emil, as both were famous Jewish physicists. Einstein wrote to Otto, telling him that if he stayed in the army, he would deprive the world of his great research into preventing human diseases. Warburg returned to his research and Einstein remained a close friend.

In 1931, he was made director of the Kaiser Wilhelm Institute for Cell Physiology in Berlin, which was renamed the Max Planck Society.  In the 1930s, Germany had one of the highest cancer rates in the world and scientists throughout Germany felt that Warburg was the world’s leading researcher most likely to produce a cure for cancer.  Hitler was a hypochondriac who believed he had cancer after having had a large polyp removed from his throat. He wanted Otto Warburg to stay in Germany so he could continue his experiments and save him from dying of cancer.  In the late 1930s, he received an offer from the Rockefeller Foundation to continue to fund his work if he emigrated to the United States.  Warburg was so dedicated to his work that he stayed in Germany despite the fates of his Jewish colleagues and relatives.

Warburg’s many Jewish students, including Hans Krebs, left Germany in the 1930s.  Krebs went on to win a Nobel Prize for working out the way human cells turn food into energy and the series of chemical reactions is called the Krebs Cycles in his honor.  He wrote that Warburg had stayed in Germany because he had spent so many years building his team of researchers and technicians that he was afraid that he would not be able to duplicate that expertise anywhere else.  Warburg continued as director of the Max Planck Institute despite his outspoken hostility toward the Nazi regime until 1941, when he was fired.  A few weeks later, he  received a personal order from Hitler’s Chancellery to resume work on his cancer research.

Warburg’s decision to work for the Nazi regime was offensive to his colleagues outside of Germany, and when he made inquiries about moving to the United States after the end of the war, he was turned down.  The Russians offered to build him an institute in Moscow, but Warburg decided to remain in Germany.   However, he fired all of his laboratory help because he believed that they had betrayed him during the war by reporting his remarks about the Nazis to the Gestapo. He maintained his post as director of the Max Planck Institute until 1970, when he died at age 87 of an “illness.’ Two years earlier, he had fallen off his horse and broken his femur,  the long bone of his upper leg.  Apparently it did not heal properly and he developed a clot in his leg that traveled to his lungs to cause a pulmonary embolism that killed him.

Over his long, productive life in research, Warburg made more than 59 major discoveries and was:

• the first to isolate flavoproteins

• the first to show that niacin is required for respiration

• the first to show many aspects of how plants use light to make chemicals

He discovered ferredoxin (the electron carrier in green plants) and demonstrated how light energy becomes chemical energy in photosynthesis.

He showed that:

• many chemicals added to food and some used in agriculture can cause cancer by interfering with how cells turn food into energy

• some cancers are preventable

• smoking cigarettes causes cancer

• cancer cells can be destroyed by radiation

• cancer cells get their energy from sugar with and without oxygen,

Today, many researchers believe that Warburg was correct in thinking that cancer cells need to use sugar for energy, which may be the key to finding a cure.This might explain why cancers are associated with diets that are high in added sugars, red meat, fried foods and excess calories that lead to weight gain and diabetes.

The best and brightest biochemists worked in Otto Warburg’s laboratory.  His students included Nobel Prize winners Otto Meyerhof, Hans Krebs, Axel Theorell, and George Wald.  My biochemistry professor at Harvard, George Wald, won his Nobel Prize for discovering vitamin A in the retina while working under Warburg in Germany from 1932 to 1933. The most famous of his students was Sir Hans Adolf Krebs, a Jewish biochemist who fled Nazi Germany in the early 1930s, went to Cambridge University in England, and won a Nobel Prize for his work showing how the body gets its energy from food (now called “the Krebs Cycle”). Diana’s father, Donald Purdie, worked with Krebs and was a professor at Cambridge and chairman of the chemistry department at Raffles College (now University of Singapore). His career ended when he was captured by the Japanese and died working on the Burma-Thai Railway (“The Death Railway).

I have written several reports based on Warburg’s work on the link between cancer and sugar; for example, see:
More Links Between Cancers and Sugar
A Cure for Cancer is Coming

October 8, 1883 – August 1, 1970