A liberal Jewish family in Königsberg
Fritz Albert Lipmann was born on June 12, 1899, in Königsberg, East Prussia, then part of Germany and now Kaliningrad in Russia. He was the second son of Leopold Lipmann, a lawyer, and Gertrud Lachmanski. The family was, in the words of one biographer, a liberal German-Jewish middle-class household in which education, the arts and social engagement mattered more than religious observance. His elder brother, Heinz, became a playwright and theatre manager.
Lipmann studied medicine from 1917 to 1922 at the universities of Königsberg, Berlin and Munich and took his medical degree in Berlin in 1924. During his first year he was gripped by what he called a dramatic chemistry course at Königsberg, and soon he was drawn to the chemistry of living things rather than to treating patients.
Apprenticeship with Meyerhof
After a fellowship in pharmacology in Amsterdam, Lipmann returned to Königsberg to study chemistry under Hans Meerwein, feeling that he needed a deeper training. In 1926 he became an assistant in the laboratory of Otto Meyerhof at the Kaiser Wilhelm Institute in Berlin-Dahlem, then one of the world’s great centres of biochemistry, and earned his doctorate there in 1927. He followed Meyerhof to Heidelberg to study the chemical reactions that power muscle.
Meyerhof’s laboratory was working out glycolysis, the breakdown of sugar, and had just discovered that certain phosphate compounds carry large amounts of energy. Lipmann absorbed both the problem and the method. In 1931 and 1932 he spent time as a Rockefeller Fellow at the Rockefeller Institute in New York, where he identified serine phosphate as the phosphate-carrying building block of phosphoproteins. In 1931 he married Elfreda Hall, known as Freda, an artist, photographer and fashion designer.
Leaving Germany
In 1932 Lipmann followed the tissue-culture pioneer Albert Fischer to Copenhagen, to the Biological Institute of the Carlsberg Foundation. Within months Hitler came to power, and the new race laws closed German academic life to Jews. Lipmann stayed in Denmark, supported by the Rockefeller Foundation, studying how cells switch between burning sugar with oxygen and fermenting it without, a puzzle known as the Pasteur effect.
In 1939, as war approached, he emigrated to the United States. He worked first at Cornell Medical College in New York and from 1941 at the Massachusetts General Hospital in Boston, where he headed his own research group. He became an American citizen in 1944.
In Copenhagen he published important papers on the Pasteur effect, the observation that cells consume much less sugar when they have oxygen than when they must ferment, and on the role of glycolysis in the cells of developing embryos. These studies of how cells regulate their fuel kept him close to the energy questions he had learned in Meyerhof’s laboratory and prepared the ground for his great synthesis of 1941.
The squiggle: energy in a bond
Lipmann’s first great contribution was an idea. In 1941 he published a long review, “Metabolic Generation and Utilization of Phosphate Bond Energy,” which gave biochemistry a unifying principle. Cells, he argued, capture the energy released by breaking down food in a few special “energy-rich” phosphate bonds, above all in adenosine triphosphate, ATP, and then spend that energy wherever it is needed: to contract muscles, build proteins, send nerve signals or make new molecules. He introduced the squiggle symbol, ~, to mark these energy-rich bonds.
The concept that ATP is the universal energy currency of the cell, earned by metabolism and spent on work, became one of the central ideas of modern biology. Every textbook explanation of how the body uses energy, from exercise physiology to nutrition, rests on the framework he set out in that essay.
Discovering coenzyme A
The road to the discovery ran through a reaction he studied with his colleague L. Constance Tuttle, who in 1944 reported with him a key reversible reaction in the breakdown of pyruvate, a product of glycolysis. Following that reaction led Lipmann to the missing factor.
In Boston Lipmann set out to find how cells activate acetate, a small two-carbon molecule produced in large amounts when sugars, fats and proteins are broken down. For years he believed the active form was acetyl phosphate and defended the idea against growing doubt. Then, in experiments from 1945 onward, he found that the reaction needed a previously unknown heat-stable factor. He isolated it, showed that it contains pantothenic acid, one of the B vitamins, and named it coenzyme A, the A standing for acetylation. By 1953 his group had worked out its structure.
Coenzyme A turned out to be the missing link in metabolism. Bound to acetate it forms acetyl-CoA, the “activated acetic acid” that feeds into the citric acid cycle discovered by Hans Krebs, the cell’s main furnace for releasing energy. As the Nobel presentation speech put it, when Lipmann announced coenzyme A, everything suddenly fitted, like the last notch of a combination lock falling into place. In 1953 Lipmann and Krebs shared the Nobel Prize in Physiology or Medicine, Lipmann “for his discovery of co-enzyme A and its importance for intermediary metabolism.”
The Nobel presentation noted a twist. Lipmann’s earlier candidate, acetyl phosphate, made a comeback when he showed that certain bacteria do use it as their active two-carbon compound. Far from feeling triumphant, the presenter said, Lipmann wrote in an otherwise serious scientific paper that he was quite happy about the finding. He and others soon showed that coenzyme A activates many other acids besides acetic acid, revealing it as a general carrier in metabolism.
Why coenzyme A matters
Acetyl-CoA is one of the most important crossroads in the body. Carbohydrates, fats and many amino acids are all broken down to it, and it is the starting material from which the body builds fatty acids, cholesterol, steroid hormones and the nerve transmitter acetylcholine. Coenzyme A also carries other acids in the burning and building of fats. Knowing this pathway is essential to understanding nutrition, obesity, diabetes, fasting and the production of ketone bodies.
It is also behind some of the world’s most widely used medicines. Statins, taken by many millions of people to lower cholesterol, work by blocking HMG-CoA reductase, an enzyme that acts on a coenzyme A compound in the pathway that makes cholesterol from acetyl-CoA. Doctors who diagnose inherited disorders of fat and organic-acid metabolism, many of which involve coenzyme A compounds, rely on the chemistry Lipmann opened up. His discovery also explained why pantothenic acid is a vitamin: the body needs it to make coenzyme A.
Harvard, Rockefeller and protein synthesis
From 1949 to 1957 Lipmann was professor of biological chemistry at Harvard Medical School, and in 1957 he moved to the Rockefeller Institute, later Rockefeller University, in New York, where he worked for the rest of his life. He kept finding new “activated” molecules: carbamyl phosphate, which the body uses to dispose of nitrogen as urea and to build the components of DNA, and the activated sulphate compounds that cells use to make sulphated sugars and other molecules.
Lipmann’s colleague Leonard Spector found an unexpectedly simple way to make carbamyl phosphate from cyanate and phosphate at room temperature, which made it far easier to prove its role. Lipmann was elected to the US National Academy of Sciences, the American Academy of Arts and Sciences and the American Philosophical Society, was a foreign member of the Royal Society and the Royal Danish Academy of Sciences, and received honorary degrees from the universities of Marseille, Chicago and Chile.
In later decades he turned to how cells build proteins. His group helped work out the stages of protein synthesis in bacteria and the elongation factors involved, and he studied the large enzyme complexes that bacteria use to assemble antibiotic peptides such as gramicidin without using the ribosome. These studies contributed to understanding how some antibiotics are made and how others work. In 1966 he received the National Medal of Science.
The man and his identity
Colleagues described Lipmann as serious, intuitive and broadly cultured, with a deep love of theatre and modern art, interests he shared with his wife. One description of his leadership was “brains but not boss”: he guided his laboratory by ideas rather than authority. The Nobel presentation called him a fighter whose only opponent was the complexity of biochemical processes. In 1971 he published an autobiography, Wanderings of a Biochemist.
Lipmann’s Jewish background shaped his path: he grew up in an assimilated German-Jewish family and could not have pursued an academic career in Nazi Germany. Like many Jewish scientists of his generation, he found refuge first elsewhere in Europe and then in the United States, which gained one of the founders of modern biochemistry. Brandeis University, founded by the American Jewish community, awarded him an honorary doctorate. He and Freda had one son, Steven, who became a professor of comparative literature.
Death and legacy
Fritz Lipmann died on July 24, 1986, in Poughkeepsie, New York, near his country home in Rhinebeck, at the age of 87. Freda Lipmann lived until 2008, dying at 101.
His legacy is woven through every account of how living things handle energy. The idea that ATP is the cell’s energy currency, the squiggle that marks an energy-rich bond, and the coenzyme that links the breakdown of food to the building of fats and cholesterol all come from him. When a doctor prescribes a statin or a nutritionist explains why we need B vitamins, they are relying on chemistry that Lipmann uncovered.
Sources & further reading
Fritz Lipmann, Biographical, NobelPrize.org · Award ceremony speech, Nobel Prize in Physiology or Medicine 1953, NobelPrize.org · Lipmann, Fritz Albert, Encyclopedia.com (Complete Dictionary of Scientific Biography) · Fritz Lipmann, Jewish Virtual Library · Fritz Albert Lipmann, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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