A Silesian childhood
Konrad Emil Bloch was born on January 21, 1912, in Neisse, a town in Upper Silesia that was then part of Germany and is now Nysa in Poland. He was the second child of Fritz Bloch and his wife Hedwig, née Striemer, a middle-class Jewish family. He went to elementary and secondary school in his home town.
In 1930 he went to Munich to study chemistry at the Technische Hochschule, the technical university. He was drawn to organic chemistry, especially the structure of natural substances, an interest he credited in large part to the inspired teaching of Hans Fischer. He also attended meetings of the Munich Chemical Society, where he heard Adolf Windaus, Heinrich Wieland and Richard Willstätter, three of the great organic chemists of the age, report on their research into steroids and enzymes. The structure of steroids, the family of molecules to which cholesterol belongs, would become his life’s work.
Forced out by the Nazis
Hitler came to power in 1933, and the new regime’s racial laws quickly closed German academic life to Jews. In the words of his Nobel biography, his studies in Munich ended in 1934 for racial reasons, just after he had obtained his degree as a Diplom-Ingenieur in chemistry. He was fortunate to find a temporary post at the Swiss Research Institute in Davos, where he studied the fatty substances of the bacteria that cause tuberculosis. It was his first experience of biochemical research.
His goal was America. According to the Harvard Gazette, a letter to the Yale biochemist John Anderson produced an appointment that helped him obtain a U.S. immigration visa; Bloch later joked that perhaps the consul was a Yale man. He arrived in the United States in 1936. In 1941 he married Lore Teutsch, a native of Munich whom he had first met there.
Learning to trace atoms
On the advice of the biochemist Max Bergmann, and with support from the Wallerstein Foundation, Bloch entered the Department of Biochemistry at Columbia University’s College of Physicians and Surgeons as a graduate student under Hans T. Clarke. He earned his doctorate in 1938. Rudolf Schoenheimer then invited him to join his research group, and those years with Schoenheimer and his colleague David Rittenberg were, Bloch said, the most influential of his apprenticeship.
Schoenheimer and Rittenberg were pioneers of a powerful new technique: labelling molecules with rare isotopes, such as heavy hydrogen or carbon-13, so that their atoms could be followed as the body broke them down and built them into new substances. It was the perfect tool for a chemist who wanted to know how living things make complex molecules. In 1942 Bloch and Rittenberg began the study of how the body makes cholesterol, work that would occupy Bloch for nearly twenty years.
Building cholesterol, atom by atom
Cholesterol is a large molecule with 27 carbon atoms arranged in four fused rings and a side chain. It is essential to life: it stiffens the membranes of every animal cell and is the raw material for bile acids and steroid hormones. But in excess in the blood it builds up in the walls of arteries and causes heart attacks and strokes. Most of the cholesterol in our blood is made by the body itself, chiefly in the liver, not taken in from food. How the body built such a complicated molecule was a mystery.
Bloch and Rittenberg showed that the starting material is acetic acid, the simple two-carbon unit of acetate. Moving to the University of Chicago in 1946, Bloch and his students fed radioactively labelled acetate to a mutant bread mould and to rats, and traced every carbon atom in cholesterol back to acetate. Over the following years Bloch, working alongside other laboratories, worked out the main stages of the route: acetate is converted into mevalonic acid, mevalonic acid into an active five-carbon unit related to isoprene, those units are joined into the long hydrocarbon squalene, squalene is folded into lanosterol, and lanosterol is trimmed to cholesterol. The German biochemist Feodor Lynen, working independently in Munich, solved crucial steps of the same pathway, including the activation of acetate and the formation of the isoprene unit.
From cholesterol to every steroid
Bloch also showed that cholesterol is itself a starting point. His laboratory found that bile acids and a female sex hormone are made from cholesterol, a finding that led to the recognition that the body’s steroid hormones are all made from it. The pathway he mapped thus connects a simple molecule from the breakdown of sugars and fats to the hormones that govern growth, reproduction and the response to stress.
At Chicago, in a department he remembered as ideal for young investigators, his group also worked out how cells use enzymes to make glutathione, a small molecule built from three amino acids that helps protect cells from chemical damage. In 1953 a Guggenheim fellowship took him to the Federal Institute of Technology in Zurich, where the ideas of Leopold Ruzicka, Vladimir Prelog and their colleagues on how terpenes and sterols are related inspired new experiments in his own laboratory. In 1954 he became Higgins Professor of Biochemistry at Harvard, a post he held until 1982, and later chaired the chemistry department. There he turned to how cells make unsaturated fatty acids and to questions of biochemical evolution, such as why the making of sterols depends on oxygen. In 1964 he and Feodor Lynen shared the Nobel Prize in Physiology or Medicine for their discoveries concerning the mechanism and regulation of cholesterol and fatty acid metabolism. His Nobel lecture was titled The Biological Synthesis of Cholesterol.
The road to statins
Bloch’s map of cholesterol synthesis became the foundation of one of the most widely used kinds of medicine in the world. The slowest, controlling step in the pathway is the conversion of a molecule called HMG-CoA into mevalonate, carried out by the enzyme HMG-CoA reductase. Once researchers understood that this step governs how much cholesterol the liver makes, they had a clear target. In the 1970s the Japanese biochemist Akira Endo found a compound from a mould that blocked the enzyme, and drug companies developed the family of medicines known as statins, among them lovastatin, simvastatin, atorvastatin and rosuvastatin.
By blocking HMG-CoA reductase, statins shut down the cholesterol production line at the step Bloch’s work had helped identify. The liver responds by pulling more cholesterol out of the blood, lowering levels of the harmful form. Statins are now taken by many millions of people to prevent heart attacks and strokes; according to a widely used organic chemistry textbook, in the decade after they came into wide use the death rate from coronary heart disease in the United States fell by a third. Bloch did not invent statins, but without the pathway he mapped, no one would have known where to aim.
A refugee scholar
Bloch was one of the many young Jewish scientists whose careers in Germany were cut short by Nazi racial policy and who went on to transform science in their new countries. His studies were ended for racial reasons when he was 22, and he crossed into Switzerland and then America with little more than a degree and an interest in natural products.
In the United States he found the teachers, colleagues and laboratories that made his work possible, among them Schoenheimer and Rittenberg. The Jewish Virtual Library describes him as a Jewish German-American biochemist and counts him among the Jewish Nobel laureates in medicine. He later received an honorary degree from the Technische Hochschule in Munich, the institution that had been forced to end his studies.
The man
Colleagues admired Bloch as both a great scientist and a cultivated man. Harvard’s dean Jeremy Knowles called him a marvelously perceptive biochemist and a wise, generous and cultivated person. He enjoyed skiing, tennis and music, valued conversations with people in fields totally remote from his own, and wrote a popular book of essays, Blondes in Venetian Paintings, the Nine-Banded Armadillo, and Other Essays in Biochemistry, published in 1994.
He and Lore lived for decades in Six Moon Hill, a modernist neighbourhood in Lexington, Massachusetts, and had two children, Peter and Susan. He was elected to the National Academy of Sciences and the American Philosophical Society, became a Foreign Member of the Royal Society in 1985 and received the National Medal of Science in 1988.
Later years and legacy
After retiring from Harvard he served as a professor at the Harvard School of Public Health from 1979 to 1984 and then held an eminent scholar chair at Florida State University. He died of complications of congestive heart failure at the Lahey Clinic in Burlington, Massachusetts, on October 15, 2000, at the age of 88. His family asked that donations be made to the Pine Street Inn, a Boston shelter for homeless people, or to Doctors Without Borders.
Konrad Bloch answered a basic question about how the body makes one of its most important molecules. That answer became the scientific foundation for statins, which protect the hearts of people around the world, and for much of what we know about steroid hormones. Harvard’s annual Konrad Bloch Lecture keeps his name alive among the biochemists who follow him.
Sources & further reading
Konrad Bloch, Biographical, NobelPrize.org · Konrad Bloch, Nobel winner, dies at 88, Harvard Gazette · Konrad Bloch, Jewish Virtual Library · Chemistry Matters: Statin Drugs, OpenStax Organic Chemistry · Konrad Bloch, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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