Hans Adolf Krebs

German biochemist

• Born: August 25, 1900; Hildesheim, Germany
• Died: November 22, 1981; Oxford, England

Krebs elucidated some of the key cycles of metabolic chemical reactions that support living organisms. The most important of these, the citric acid cycle, is found in all living organisms. Also known as the Krebs cycle, this complex sequence of reactions is central to the study of metabolism.

Primary fields: Chemistry; biology

Specialty: Biochemistry

Early Life

Hans Adolf Krebs grew up in the small provincial German town of Hildesheim. His father, Georg Krebs, was a successful ear, nose, and throat surgeon, and the family schedule revolved around the elder Krebs’s professional life. The family was cared for by his wife, Alma Davidson Krebs, along with a cook and housemaid. Young Hans, his older sister Lisa, and his younger brother Wolf were raised in the strict manner of the times and were taken on Sunday walks, during which Georg Krebs instructed his children in the names of wildflowers. Hans Krebs developed a genuine interest in flowers, though he was less excited about the daylong hikes.

As a child, Krebs was educated at local schools and received a great deal of stimulation from his family and community. His father had a wide range of interests and encouraged his children to take an active part in family discussions.

Following brief military service at the end of World War I, Krebs began studies in medicine at the University of Göttingen in 1918. After furthering his studies in Berlin, Freiburg, and Munich, Krebs received an MD at Hamburg in 1925. He was particularly impressed by biochemist Franz Knoop, a lecturer at Freiburg who had made significant progress toward understanding how chemistry actually operates in cells. One of the most important events of Krebs’s early career occurred in 1926, when he became the assistant to biochemist Otto Warburg (winner of the Nobel Prize in Physiology or Medicine in 1931) at the Kaiser-Wihelm Institute in Berlin. Krebs would remain in this post until 1930, when he returned to clinical medicine.

Life’s Work

Krebs practiced medicine between 1930 and 1933 at the Municipal Hospital of Altona and the University of Freiburg clinic. Around the same time, biochemistry was just beginning to unravel scientific issues relating to metabolism—the complicated means by which cells break down foodstuffs, such as carbohydrates, into the energy required for life. In Warburg’s laboratory, Krebs had been introduced to the technique of using thin sections of tissue in an elegant instrument called the Warburg apparatus. This instrument provided an accurate measurement of tissue respiration—the chemical process by which tissues are supplied with the oxygen necessary for metabolism. Since much of metabolism consists of the oxidation of carbon molecules into carbon dioxide and water, this approach was ideal for studying this kind of chemical transformation.

Of central importance to Krebs’s study of metabolism was determining how living organisms convert toxic ammonia (formed in the metabolism of amino acids derived from proteins) into urea, a harmless compound that is excreted in urine. Krebs discovered the chemical reactions that are now referred to as the urea cycle. Observation indicated that the final product of this sequence of reactions was also the starting material for the first step—in other words, the sequence of reactions was a cycle. The cyclic nature of biochemical processes is what makes them so efficient. Krebs’s work allowed scientists to understand the biological functions of amino acids, which had been identified but whose functions had been misinterpreted. With the help of a medical student, Kurt Henseleit, Krebs was able to publish his results in “The Ornithine Cycle of Urea Synthesis” in 1932. In the following year, he continued to expand and demonstrate the significance of the discovery.

In the early 1930s, Germany was being torn apart by severe economic and political unrest. After the Nazi Party came to power in 1933, it implemented anti-Semitic policies that resulted in the dismissal of Jewish scientists and teachers from their posts. Krebs was informed that he was being placed on leave and was forbidden to see his patients; later, he was ordered to stop all laboratory work. While Krebs considered himself a Jew only by descent, his professional life in Germany became untenable. He considered an invitation from Czech biochemist Carl Cori to join him at Washington University in St. Louis, Missouri; ultimately, however, Krebs chose to emigrate to England, where he worked as a demonstrator in biochemistry at Cambridge University and a lecturer in biochemistry at the University of Sheffield. In 1945, he became professor and director of medical research at Sheffield. In 1954, he moved to the University of Oxford as the Whitley Professor of Biochemistry.

During these tumultuous years, Krebs made what many biochemists consider the most important discovery in metabolic chemistry: the operation of glucose metabolism. It was already known that a two-carbon unit, called the acetyl group, reacts with a four-carbon unit, called oxaloacetate, to form citric acid. But how this initial reaction proceeded to form carbon dioxide was little understood. In 1937, using the apparatus and techniques that had been successful in describing the urea cycle, Krebs was able to show that this process also consisted of a cycle—the citric acid cycle. His cyclic model demonstrated how acids generated in the breakdown of sugars then regenerate through compounds and provoke chemical energy. Krebs’s discovery proved crucial to understanding the means by which organisms derive energy from food.

What came to be known as the Krebs cycle consists of a series of eight stages, in which the final step supplies the oxaloacetate required for the beginning of the next cycle. Each of these reactions is controlled by one or more enzymes accompanied by various coenzymes. These substances act together to speed up chemical change and prevent undesirable alternative reactions. Krebs was able to show that the reactions he postulated occurred at rates sufficient to parallel observable processes in living cells. While such experiments did not prove that his explanation was correct, they did show that his explanation was consistent with the outcome.

For his groundbreaking work, Krebs was awarded the Nobel Prize in Physiology or Medicine in 1953, along with Fritz Lipmann of Harvard, who greatly extended Krebs’s original work. Krebs was knighted by Queen Elizabeth II in 1958. He died in Oxford in 1981 at the age of eighty-one.

Impact

Krebs provided a vital link between biology and chemistry, helping to foster the new science of biochemistry. His other contributions included developing and using precise instruments and techniques for examining metabolic reactions. Krebs’s legacy is most apparent, however, in his experiments on the cyclical nature of metabolism. Working within the basic limits of his laboratory results, Krebs proposed a scheme that has withstood many years of study and many attempts to refute its structure. Subsequent studies have added detail and shown that the Krebs cycle is found in essentially all living organisms. An improved interpretation of the experimental evidence has yet to be found. Throughout his life, Krebs remained a modest and dedicated research scientist. His pioneering work in biochemistry laid the groundwork for further work in the field of medical research. After his retirement in 1967, Krebs continued his research in genetic diseases caused by defective enzymes.

Bibliography

Holmes, Frederic Lawrence. Hans Krebs: The Formation of a Scientific Life, 1900–1933. New York: Oxford UP, 1991. Print. The first of a two-volume biography, narrates Krebs’s biography from childhood through his discovery of the urea cycle in the early 1930s, drawing from Krebs’s laboratory notebooks and personal interviews.

---. Investigative Pathways: Patterns and Stages in the Careers of Experimental Scientists. New Haven: Yale UP, 2004. Print. Investigates the paths that different scientists have taken over the past three hundred years, finding common aspects in their pursuit of scientific knowledge. Includes a section devoted to Krebs.

Lightman, Alan. The Discoveries: Breakthroughs in Twentieth-Century Science, Including the Original Papers. New York: Vintage, 2010. Print. Reproduces and discusses documents pertaining to significant scientific discoveries, including the discovery of the Krebs cycle. Includes the 1937 publication in which Krebs and his colleague W. A. Johnson describe citric acid’s role in metabolism.