Otto Heinrich Warburg

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Reader's Guide

Warburg's significance lies in his pioneering work on cellular respiration and cancer metabolism. He discovered that animal tumors produce large quantities of lactic acid, leading to his hypothesis that cancer is caused by a shift from oxidative respiration to fermentation of sugar—a concept now known as the Warburg effect. Although modern cancer biology attributes malignant transformation primarily to genetic mutations, Warburg's metabolic insights remain influential in cancer research and systems biology. Three of his laboratory alumni, including Sir Hans Adolf Krebs, later won Nobel Prizes. Warburg's legacy endures in the ongoing study of mitochondrial dysfunction and metabolic reprogramming in cancer.

Did You Know?

• He was nominated for the Nobel Prize 47 times over his career.
• During the First World War, he served as an officer in the elite Uhlans cavalry and won the Iron Cross (1st Class).
• He lived with his personal assistant Jacob Heiss in a villa in Berlin-Dahlem.

Scientific Breakthroughs and the Science of Cellular Energy

Krebs devoted his career to unraveling how living cells extract usable energy from the food and oxygen they consume. Working first as a research assistant under Otto Heinrich Warburg at the Kaiser Wilhelm Institute in Berlin, he produced sixteen publications in just four years before his mentor encouraged him to seek independent work. At the University of Freiburg, he and graduate student Kurt Henseleit identified the ornithine pathway of urea synthesis, a metabolic route now universally called the urea cycle. Their work also yielded a specialized aqueous buffer solution for studying arterial blood flow outside the body, still referenced in laboratories today. His most celebrated achievement came later: the elucidation of the citric acid cycle, a sequence of reactions that enables oxygen-breathing organisms to harvest far more cellular energy in the form of ATP than anaerobic pathways like glycolysis can provide. This discovery earned him the 1953 Nobel Prize in Physiology or Medicine. Together with Hans Kornberg, he also identified the glyoxylate cycle, a variant of the citric acid cycle operating in plants, fungi, bacteria, and protists. Collectively, these findings made him a foundational figure in the study of cellular respiration.

Persecution, Exile, and a Narrow Escape

Krebs was of Jewish ancestry, and that single fact would shatter his promising career in Germany. When the Nazi Party seized power in 1933, the new regime enacted the Law for the Restoration of the Professional Civil Service, which mandated the removal of non-Aryans and political opponents from all professional positions. Krebs received his formal dismissal notice in April of that year, and his employment was officially terminated by July. His escape from the country was swift but desperate. The renowned biochemist Sir Frederick Gowland Hopkins at Cambridge intervened on his behalf, persuading the university to take him into its Department of Biochemistry. Financial backing from the Rockefeller Foundation helped sustain him during the transition. Crucially, German authorities permitted him to carry his personal laboratory equipment and research samples across the border. Among those items was a manometer originally designed by Warburg for measuring oxygen consumption in thin tissue slices, an instrument that would prove indispensable to Krebs's subsequent breakthroughs. By July 1933 he was settled in Cambridge, and his scientific life in Britain was underway.

Building a Laboratory Empire at Sheffield

In 1935 Krebs accepted a lectureship in pharmacology at the University of Sheffield, drawn by a larger laboratory and a salary twice what Cambridge offered. What began as a modest appointment grew into nearly two decades of transformative institutional building. In 1938 the university established a dedicated Department of Biochemistry, and Krebs was named its inaugural head; he was elevated to full professorship in 1945. Under his stewardship the department evolved into one of the preeminent centers of biochemistry worldwide. His responsibilities continued to expand: in 1943 he assumed direction of the Sorby Research Institute, and the following year the British Medical Research Council founded a Unit for Cell Metabolism Research at Sheffield, appointing Krebs as its director. The laboratory grew so large in scope and staff that local residents took to calling it "Krebs's Empire." The department, now known as the Department of Molecular Biology and Biotechnology, carried forward the tradition he established. His tenure at Sheffield represented the longest single institutional commitment of his career and the period during which his reputation as a world-class biochemist was firmly cemented.

Oxford, Retirement, and a Lasting Scientific Imprint

In 1954 Krebs relocated his MRC unit to the University of Oxford, taking up the Whitley Professorship of Biochemistry, a post he held until his retirement in 1967. Even after stepping down from his professorial role, he remained actively engaged in research, transferring his unit to the Nuffield Department of Clinical Medicine at the Radcliffe Infirmary. When the editorial board of the Biochemical Journal extended their congratulations on his retirement, Krebs humorously pledged to keep them occupied with continued scientific publications, a promise he evidently intended to honor. His broader legacy extends well beyond any single institution. The citric acid cycle bears his name and remains a cornerstone of biochemistry taught in every biology curriculum. The Krebs-Henseleit buffer continues to be a practical tool in physiological research. His work on cellular respiration fundamentally reshaped how scientists understand energy metabolism in nearly all aerobic organisms. Krebs passed away in Oxford in 1981, the same city where he had spent the final thirteen years of his professional life.