- Person
- William H. Stein
- Lived
- 1911–1980
- Field
- Biochemistry
- From
- American
The story
To understand a protein, scientists first need to know which of the twenty kinds of amino acid it contains and in what amounts. In the 1930s and 1940s there was no accurate way to find out. William H. Stein, born in New York City in 1911 to a Jewish family active in the city’s health causes, and his colleague Stanford Moore set out to solve the problem at the Rockefeller Institute for Medical Research after the Second World War.
Following a suggestion from the British chemist Richard Synge, they first separated amino acids on columns of potato starch and measured each fraction with a colour reaction using ninhydrin. To handle hundreds of fractions they invented a drop-counting automatic fraction collector, which Stein later noted became standard equipment in biochemical laboratories around the world. The starch method took about two weeks per protein. Switching to ion-exchange resins cut that to about a week. Then, working with Darrel Spackman, they automated the whole process. In 1958 they introduced the first automatic amino acid analyzer, a combination of pumps, columns, a heated reaction coil, a photometer and a chart recorder that ran overnight and drew the results as a series of peaks.
They put it straight to use. Moore, Stein and their team determined the complete sequence of the enzyme ribonuclease by 1960, the first enzyme ever sequenced and the first protein sequence worked out with the help of automation. They also found that groups in the enzyme’s active site were unusually reactive and used this to locate them, giving, as the Swedish Academy said, a detailed picture of the active site long before its 3D structure was known. Stein, Moore and Christian Anfinsen shared the 1972 Nobel Prize in Chemistry.
Beckman Instruments commercialized the analyzer, and it spread to laboratories everywhere. Stein used it to study amino acids in human blood plasma and urine, and measuring amino acids in body fluids became an important medical tool, including for investigating inherited metabolic disorders. Stein insisted the methods grew out of need, not a desire to build machines for their own sake.
Why it matters
Moore and Stein’s analyzer and methods made protein analysis routine in research, biotechnology and clinical laboratories.
About William H. Stein
New York biochemist who, with Stanford Moore, built the automatic amino acid analyzer and decoded the first enzyme sequence, making protein analysis routine in medicine and biotech. Nobel 1972.
Sources
- William H. Stein, Biographical NobelPrize.org
- Press release: The Nobel Prize in Chemistry 1972 NobelPrize.org
- The First Automated Amino Acid Analyzer The Scientist
- William Howard Stein Wikipedia
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