Otto Warburg found that cancer cells crave sugar

Person

Otto Warburg

Lived

1883–1970

Field

Biochemistry

From

German

The story

Most healthy cells get their energy by splitting glucose through glycolysis and then burning the products completely with oxygen inside their mitochondria, a process that releases a large amount of energy. In the early 1920s Otto Warburg, a professor at the Kaiser Wilhelm Institute for Biology in Berlin-Dahlem, turned his attention to tumours and asked whether their chemistry differed from that of normal tissue.

Beginning in 1922, using thin slices of tissue and the sensitive pressure gauges he had designed himself, Warburg and his group measured how tumour tissue handled sugar. They found that cancer cells took up glucose greedily and turned much of it into lactic acid, and that they kept doing so even when there was plenty of oxygen for normal respiration. The effect appeared both in the test tube and in living animals, though its strength varied from one cancer to another. By contrast, no growing normal tissue he examined produced lactic acid from glucose in the presence of oxygen. He gathered the results in a 1926 book, published in English in 1930 as The Metabolism of Tumours.

Warburg called the pattern aerobic glycolysis, and later scientists named it the Warburg effect. It proved to be a common feature of many cancers. Warburg went further and argued that damaged respiration was the prime cause of cancer, a view he defended in lectures for the rest of his life. Later research showed that cancer is driven mainly by mutations in oncogenes and tumour suppressor genes, and the metabolic shift is now generally seen as a result of those mutations rather than their cause. His central observation, however, has stood the test of time.

Why tumours behave this way is still debated. One leading idea is that fermenting sugar, though a wasteful way to make energy, lets fast-growing cells keep more of the carbon from their food for building new cell material. Others point to low oxygen levels inside tumours, or to cancer genes that turn mitochondria down.

The Warburg effect has also become a practical tool. Because tumours absorb so much glucose, a radioactive glucose analogue injected before a PET scan collects in them and reveals where they are. Researchers have tested drugs that block glycolysis, such as 2-deoxy-D-glucose and dichloroacetate, and although no such treatment has yet proved itself, cancer metabolism remains an active field. A discovery made with glass flasks and pressure gauges a century ago still shapes the questions cancer biologists ask.

Why it matters

The Warburg effect is one of the best-known features of cancer biology and remains a guide for researchers searching for ways to detect and treat tumours.

About Otto Warburg

Biochemist who uncovered how cells breathe and discovered that tumours burn sugar by fermentation, the “Warburg effect”; Nobel laureate in 1931 who kept working in Nazi Berlin as a “Mischling.”

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Otto Warburg

1883–1970 · Biochemistry

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More about Otto Warburg

• Otto Warburg's discovery lets PET scans find tumoursPET scans locate cancers by tracking a radioactive form of glucose that tumours absorb in excess, putting Otto Warburg's century-old discovery to work in hospitals every day.
• Otto Warburg used light to unmask an invisible enzymeOtto Warburg showed that carbon monoxide blocks cell breathing and that light lifts the block, and used this trick to read the chemical signature of the respiratory enzyme.
• Otto Warburg built the tools of modern biochemistryOtto Warburg introduced the thin tissue-slice technique in 1923 and refined manometric methods for measuring how living tissue consumes oxygen, tools used in labs for decades.
• Otto Warburg discovered how cells use oxygenOtto Warburg identified the iron-containing enzyme that lets living cells use oxygen, winning the unshared 1931 Nobel Prize in Physiology or Medicine.
• Otto Warburg measured life's first breath in an eggWorking at the Naples marine station before the First World War, Otto Warburg showed that a sea urchin egg's respiration rises sharply the moment it is fertilised.
• Otto Warburg revealed the helper molecules of metabolismIn the 1930s Otto Warburg discovered the yellow enzymes and identified flavin and nicotinamide as the active parts of the enzymes that move hydrogen in living cells.

Sources

• Warburg effect (oncology) Wikipedia
• Otto Heinrich Warburg Wikipedia

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