Awards & Honors

Nobel Laureates

William H. Stein

(1911—1980)

1972 Nobel Prize in Chemistry

Early in the 19th century, Swedish chemist Jöns Jacob Berzelius introduced the idea of catalysis — the process by which a chemical substance contributes to a chemical reaction without being changed by it — and suggested that the tissues of all living organisms function through catalytic activity. By the turn of the 20th century, scientists had identified those catalysts as enzymes. Everything we do — motor tasks, decision making, emotional responses — is at its most basic level accomplished by means of enzyme reactions. In the 1940s and '50s, William H. Stein and his colleague Stanford Moore, two members of The Rockefeller Institute for Medical Research, broke open the field of biochemistry by theorizing how each individual enzyme is programmed to accomplish its own unique catalytic task. They then proved their theories with ribonuclease, an essential regulator of RNA, which translates the genetic information locked in our DNA. For these contributions, Drs. Stein and Moore were awarded the 1972 Nobel Prize in Chemistry.

Proteins, including enzymes, are constructed of amino acids — small compounds of carbon, hydrogen, oxygen and nitrogen. There are 20 different amino acids used by cells in various combinations to create proteins; insulin, for example, is made of 16 amino acids, many of them repeated in a peptide sequence that contains altogether 51 amino acids. This simple mechanism of variation alone explains the ability of an organism to create a myriad of proteins with palpably different structures, like casein, gelatin and silk, and widely varying functions, including hormones, antibodies and enzymes. Drs. Stein and Moore's main question when they joined Rockefeller concerned how two proteins composed of the same amino acids can have such completely different characteristics and functions. Their hypothesis was that, much like the letters of an alphabet, amino acids have more meaning in their relationship to each other than they do separately, and that the function of a protein is determined by the sequence in which it is arranged.

The first step in determining the sequence of a particular protein was, for Drs. Stein and Moore, to disassemble it. During their first few years at Rockefeller, in the late 1930s, they examined the action of various peptidases and proteinases — naturally occurring enzymes whose function is to break down specific proteins and peptide sequences — to ascertain exactly how they target individual molecules and how they split them apart. They devised numerous methods for artificial catabolism, some of which are still in use today.

Their next step was to identify the now separated components in the "enzyme soup" they had effectively created. They utilized a method known as partition chromatography, whereby they passed their indistinguishable mixture through a porous material — in this case, a glass tube filled with potato starch — which causes the constituent elements to separate from each other and form distinct groups. They then employed a reagent in order to measure the number of amino acids in each group. Over the next several years, Drs. Stein and Moore greatly improved upon this method, and eventually used it to analyze the amino acid content of many biologically significant proteins.

Through continuing experiments, Drs. Stein and Moore discovered several crucial facts about the alphabet of amino acids and the patterns into which they are folded. The structure of an enzyme, they found, is of little importance in determining its specific catalytic activity if the active site of the peptide sequence has not been located. They then devised a way to locate the active site of an enzyme without solving its structure and discovered that the amino acids of the active site are more reactive than the same amino acids in free form. In addition to the research implications of these discoveries, Drs. Stein and Moore contributed to medical science: Their experimental methods offered physicians a way to determine the amino acid constitution of blood serum and of human urine, a now common diagnostic technique for many diseases. Drs. Stein and Moore shared the 1972 Nobel Prize with Christian B. Anfinsen of the National Institutes of Health.

CAREER

Born in New York City in 1911, Dr. Stein received his Ph.D. in biochemistry from the Columbia University College of Physicians and Surgeons in 1937. Next, he joined the laboratory of Max Bergmann at The Rockefeller Institute, at the time renowned for its innovative research on the chemistry of proteins and enzymes, and there met and began his collaboration with Dr. Moore. Following World War II and the death of Dr. Bergmann, Drs Stein and Moore joined the lab of institute director Herbert Gasser and continued their work in the amino acid analysis of proteins. Dr. Stein was on the editorial staff of the Journal of Biological Chemistry for several years. He was a member of the National Academy of Sciences and the American Chemical Society and received, in addition to the Nobel Prize, the Award in Chromatography and Electrophoresis and the Richards Medal from the ACS. Dr. Stein died in 1980.