The Secrets of Cholesterol

First, incomplete medical research suggested that a mysterious substance called cholesterol was a root cause of much artery disease and many heart attacks. Then, after more complicated studies, the researchers said no, maybe cholesterol itself was not very important. The one conclusion that the public could safely draw was that medical science needed to learn a great deal more about what cholesterol does, where it comes from and how and where it goes. For taking innumerable small but important steps toward that vital goal, two biochemists, an American and a German, last week shared the 1964 Nobel Prize (worth $53,000) in physiology and medicine.

Four-Ring Cluster. The American is Harvard's Konrad Emil Bloch, 52, who came to biochemistry via chemical engineering. Early in his research Dr. Bloch learned that most of the cholesterol in the bodies of both animals and men comes not from cholesterol in food (though butterfat, egg yolks and meat fats contain much of it) but from built-in cholesterol factories. These factories are mainly in the liver, but many of the body's other cells can make some cholesterol. To discover how they do it, Dr. Bloch had to go back to the biochemical beginning.

Cholesterol is a steroid, one of a huge and diverse class of chemicals--including many fatty substances and most adrenal and sex hormones--having one thing in common: a four-ring cluster of carbon atoms, known as "the steroid nucleus." Other attached atoms give each steroid its distinctive character (see diagram). By growing rat-liver cells in the test tube, Dr. Bloch learned that they make cholesterol from the much simpler acetate ion (acetic acid minus a hydrogen ion). "My work since then," he says, "has been on the processes that the cell uses to manufacture the cholesterol molecule. This is a fantastically complex sequence of approximately 36 biochemical reactions." Bloch adds with a grin: "It was a great temptation to call it The 39 Steps,' and it may turn out that there are 39, but we were afraid this might be lost on the younger generation."

Born a German in Neisse (now in Poland), Bloch graduated from Munich's Technische Hochschule in 1934. Because he was a Jew, he was not allowed to continue his studies. He spent two years in Switzerland, came to the U.S. in 1936, got his Ph.D. at Columbia in 1939, was naturalized in 1944. After an eight-year stint at the University of Chicago, he became Harvard's Higgins professor of biochemistry.

Firm Foundation. Feodor Lynen, 53, head of biochemistry at the University of Munich and director of the Max-Planck-Institut fuer Zellchemie, is the son of a chemistry professor and married to the daughter of another, Heinrich Wieland, who won a Nobel Prize in chemistry in 1927. For years, until after World War II, Lynen's cholesterol work paralleled Bloch's without either man's knowing what the other was doing. When they began to publish results, it became clear that the two labs were working toward the same goal, but their approaches were different, and Dr. Lynen's Nobel citation singled out an aspect of his work that definitely does not overlap Bloch's: "His recent discovery of the biochemistry by which the vitamin biotin acts, which is fundamental in lipid [fat] metabolism, is in itself a discovery with the most far-reaching implications."

Sweden's Royal Caroline Institute, the medical school that is responsible for selecting Nobel winners in physiology and medicine, was understandably careful not to go out on a limb because of the raging controversies over cholesterol and cooking fats. But it declared: "Circulatory diseases are the foremost cause of death in many areas of the world. The great majority of these cases have a gravely disturbed lipid metabolism. The prerequisite for correcting a faulty function is to know the intimate details of the mechanisms involved. The therapy against these circulatory diseases and related disturbances in steroid hormone metabolism will in the future rest upon the firm foundation laid by Bloch and Lynen."

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