A doctor’s son in Hildesheim
Hans Adolf Krebs was born on August 25, 1900, in Hildesheim, in the Prussian province of Hanover, the middle of three children. His father, Georg Krebs, was an ear, nose and throat surgeon with a flourishing practice; his mother, Alma Davidson, came from a banking family long settled in the Hildesheim area. Both parents came from Jewish families, but they raised their children without religious practice. Georg Krebs believed that the answer to the so-called Jewish question in Germany was assimilation, and he was thoroughly immersed in German culture.
Hans was a shy, solitary boy who practised the piano for hours and loved nature, botany and bookbinding. His father was distant and doubted his abilities. He attended the Gymnasium Andreanum in Hildesheim, and in September 1918, six months before finishing, he was conscripted into the German army. The war ended two months later.
Training with a master
Krebs studied medicine at the universities of Göttingen, Freiburg and Berlin between 1918 and 1923, then spent a year at the Third Medical Clinic of the University of Berlin and took his medical degree at the University of Hamburg in 1925. Realising that he needed chemistry to answer the questions that interested him, he spent a further year studying it in Berlin.
In 1926 he became assistant to Otto Warburg at the Kaiser Wilhelm Institute for Biology in Berlin-Dahlem, one of the most demanding and brilliant biochemists of the age. Warburg ran a six-day week and an authoritarian laboratory, but Krebs absorbed his insistence on central questions and precise methods. He learned to keep thin slices of living tissue alive in a flask and to measure their oxygen use with Warburg’s manometer, the tools that would make his name. When Warburg refused to let him study how cells break down food, Krebs left in 1930 to return to hospital medicine, first in Altona and then at the University of Freiburg.
The first metabolic cycle
At Freiburg, while also seeing patients, Krebs set up experiments on how the liver makes urea, the main way the body gets rid of toxic nitrogen from protein. With a medical student, Kurt Henseleit, he found that adding a substance called ornithine sharply increased the amount of urea made by liver slices, far more than ornithine itself could account for. In 1932 he proposed that ornithine was being used and regenerated in a loop: the urea cycle, also called the Krebs–Henseleit cycle.
It was the first metabolic cycle ever described, a new idea in biochemistry: a chain of reactions that ends by remaking the molecule it started with, so that a small amount can process a large quantity of material. The urea cycle is now central to understanding liver disease and a group of inherited disorders in which babies cannot clear ammonia from their blood.
The discovery came quickly. Krebs and Henseleit showed early in 1932 that the effect of ornithine was specific and catalytic, and that spring Krebs proposed the cyclic pathway, which he called in German the Kreislauf des Ornithins. They also devised a salt solution for keeping tissues alive in the laboratory, the Krebs–Henseleit buffer, which is still used in research. The work earned him a lecturing post at Freiburg in December 1932, only weeks before Hitler came to power.
Dismissed
Weeks after the Nazis came to power, the Law for the Restoration of the Professional Civil Service removed Jews from public posts. Krebs was suspended in April 1933 and dismissed that summer from all his duties at Freiburg. His family had long since left Jewish religious life, and some accounts say he had formally left the Jewish community years before, but under Nazi law that made no difference.
Sir Frederick Gowland Hopkins, the founder of British biochemistry, invited him to Cambridge, and with a Rockefeller Foundation studentship he arrived in June 1933. Unusually, the German authorities let him take his equipment and research samples, including the Warburg manometers that were central to his work. In 1935 he moved to the University of Sheffield, where he would spend what he called nineteen happy years. He became a British citizen in 1939.
The cycle of life
At Sheffield Krebs turned to the great unsolved question of how cells burn food for energy. Scientists knew many of the individual reactions, but not how they fitted together. Working with his student William Arthur Johnson on minced pigeon breast muscle, which burns fuel fast, he found that small amounts of citric acid made the muscle consume far more oxygen than the citric acid itself could explain. In 1937, combining this with recent work by Carl Martius and Franz Knoop, he assembled the whole sequence within weeks: a loop of reactions in which fragments of food molecules are joined to a carrier, stripped of their energy step by step, and released as carbon dioxide while the carrier is regenerated to go round again.
In June 1937 he sent a short paper to Nature. The editor replied that the journal already had enough letters to fill its correspondence columns for seven or eight weeks. Krebs sent a fuller version to the Dutch journal Enzymologia, which published it quickly. The citric acid cycle, also called the tricarboxylic acid cycle or simply the Krebs cycle, became one of the most famous discoveries in biology. Ten years later Fritz Lipmann discovered coenzyme A, the molecule that feeds fuel into the cycle, and in 1953 the two men shared the Nobel Prize in Physiology or Medicine.
Why it matters
The Krebs cycle runs inside the mitochondria of almost every cell in the body. Sugars, fats and proteins are all broken down into fragments that enter the same cycle, which captures the energy that powers muscles, nerves and every other living process. It is the central hub of metabolism, connecting the breakdown of food with the building of new molecules, and it is taught to virtually every student of biology and medicine in the world.
Understanding the cycle made it possible to understand what goes wrong in many diseases, from rare inherited defects of energy production to diabetes, and researchers today study how cancer cells rewire it to fuel their growth. Krebs’s method of thinking in cycles, in which pathways loop back on themselves, also became a basic way of understanding how living systems regulate themselves.
Sheffield, Oxford and the knighthood
In 1938 Krebs married Margaret Cicely Fieldhouse, a domestic science teacher from Wickersley in Yorkshire; they had three children, Paul, Helen and John. That year he became head of Sheffield’s new Department of Biochemistry, and in 1945 professor and director of a Medical Research Council unit for research in cell metabolism. During the Second World War he ran nutrition experiments with volunteer conscientious objectors.
In 1954 he became Whitley Professor of Biochemistry at Oxford, bringing his research unit with him. With Hans Kornberg he described the glyoxylate cycle, a variant used by plants and bacteria, and wrote an influential survey of energy in living things. He was elected a Fellow of the Royal Society in 1947 and knighted in 1958. Among his many honorary degrees was one from the Hebrew University of Jerusalem.
His honours included the Lasker Award in 1953, the Royal Society’s Royal Medal in 1954 and its highest award, the Copley Medal, in 1961, and honorary doctorates from some twenty-one universities. In 2015 his Nobel medal was sold at auction for £225,000 to fund the Sir Hans Krebs Trust, which supports research and young scientists.
His research ranged well beyond the two cycles that bear his name. He studied how birds make uric acid and the building blocks of DNA, how cells pump salts across their membranes, and how the energy released by burning food is captured in the cell’s energy-carrying molecules. In later years he turned to how metabolism is controlled, including how the liver makes new glucose when the body is fasting.
The man
Colleagues described Krebs as disciplined, hard to please and sparing with praise, yet loyal, generous with help and modest about his fame. He was more gifted at designing experiments than carrying them out, and from the late 1930s relied on skilled collaborators. He disliked the very idea of retirement.
Required to retire from his chair at sixty-seven in 1967, he moved to a small laboratory at the Radcliffe Infirmary in Oxford and kept working, publishing more than a hundred further papers. His son John became a distinguished ornithologist, an Oxford professor and Principal of Jesus College, Oxford, and entered the House of Lords as Lord Krebs.
Even in his last years he kept asking why the cycle he had found was built the way it was. In 1980, prompted by a suggestion from the Oxford chemist Jack Baldwin, he worked on an explanation of why the citric acid cycle is such an efficient route for extracting energy. He once remarked that metabolic cycles seem to be a feature peculiar to life.
Last years and legacy
Krebs remained active until September 1981. After a brief illness he died in Oxford on November 22, 1981, aged 81. His autobiography, Reminiscences and Reflections, appeared that year.
His life is one of the clearest examples of what Germany lost and Britain gained when the Nazis drove Jewish scientists from their posts. The young doctor dismissed from Freiburg in 1933 went on, within four years and in a provincial English university, to make the discovery that now stands at the centre of every biochemistry textbook. Every cell that burns food for energy relies on the cycle that bears his name.
Sources & further reading
Hans Krebs, Biographical, NobelPrize.org · Krebs, Hans Adolf, Complete Dictionary of Scientific Biography, Encyclopedia.com · Hans Krebs (biochemist), Wikipedia · Jewish Nobel Prize Winners in Physiology or Medicine, JINFO.org · Researched from the sources above and checked against them. Spotted an error? Tell us.
A life of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.