World of Scientific Discovery on William Howard Stein
William Howard Stein, in partnership with Stanford Moore, was a pioneer in the field of protein chemistry. Although other scientists had previously established that proteins could play such roles as that of enzymes, antibodies, hormones, and oxygen carriers, almost nothing was known of their chemical makeup. Stein and Moore, during some forty years of collaboration, were not only able to provide information about the inner workings of protein molecules, but also invented the mechanical means by which that information could be extracted. Their discovery of how protein amino acids function was accomplished through a study of ribonuclease (RNase), a pancreatic enzyme that assists in the digestion of food by catalyzing the breakdown of nucleic acids. But their work could not have been accomplished without the development of a technology to assist them in collecting and separating the amino acids contained in ribonuclease. Their invention of the fraction collector and an automated system for analyzing amino acids was of great importance in furthering protein research, and these devices have become standard laboratory equipment.
Stein and Moore began their collective work in the late 1930s under Max Bergmann at the Rockefeller Institute (now Rockefeller University). After Bergmann's death in 1944, the pair developed the protein chemistry program at the Institute and began their research into enzyme analysis. Except for a brief period during World War II when Moore served with the Office of Scientific Research and Development in Washington D.C., and the two years when Stein taught at the University of Chicago and Harvard University, the partnership continued uninterrupted until Stein's death in 1980. Their joint inventions and co-authorship of most of their scientific papers were said to make it impossible to separate their individual accomplishments. Their combined efforts were acknowledged in 1972 with the Nobel Prize in chemistry. According to Moore, writing about Stein in the Journal of Biological Chemistry in 1980, they received the award "for contributions to the knowledge of the chemical structure and catalytic function of bovine pancreatic ribonuclease." Christian Anfinsen shared the Nobel Prize with Stein and Moore for related research.
The son of community-minded parents, Stein was born in New York City on June 25, 1911. From an early age, Stein was encouraged by his parents to develop an interest in science. He received a progressive education from grade school on, attending the Lincoln School of the Teacher's College of Columbia University, transferring at sixteen years of age to Phillips Exeter Academy for his college preparatory studies. He graduated from Harvard University in 1933, then took a year of graduate study in organic chemistry there. Finding that his real interest was biochemistry, he completed his graduate studies at Columbia University, receiving his Ph.D. in 1938. His dissertation concerned the amino acid composition of elastin, a protein found in the walls of veins and arteries. This work marks the beginning of his long search to understand the chemical function of proteins.
The successful research being done at the Rockefeller Institute under the direction of Max Bergmann caught Stein's attention. He pursued post-graduate studies there in 1938, spending his time improving analytical techniques for purifying amino acids. Moore joined Bergmann's group in 1939. There, he and Stein began work in developing the methodology for analyzing the amino acids glycine and leucine. Their work was interrupted when the United States entered World War II. Then, Bergmann's laboratory was given over to the study of the physiological effects of mustard gases, in the hope of finding a counteractant.
The group's efforts to find accurate tools and methods for the study of amino acid structure increased in importance when they assumed the responsibility of establishing the Institute's first program in protein chemistry. Looking for ways to improve the separation process of amino acids, they turned to partition chromatography, a filtering technique developed during the war by the English biochemists A. J. P. Martin and Richard Synge. Building on this technology, as well as that of English biochemist Frederick Sanger' s column chromatography and the ion-exchange technique of Werner Hirs, Stein and Moore went on to invent the automatic fraction collector and develop the automated system by which amino acids could be quickly analyzed. This automated system replaced the tedious two-week sequence that was previously required to differentiate and separate each amino acid.
From then on, the isolation and study of amino acid structure was advanced through these new analytical tools. Ribonuclease was the first enzyme for which the biochemical function was determined. The discovery that the amino acid sequence was a three-dimensional, chain-like structure that folds and bends to cause a catalytic reaction was a beginning for understanding the complex nature of enzyme catalysis. Stein and Moore were certain that this understanding would result in crucial medical advances. By 1972, the year Stein and Moore shared the Nobel Prize, other enzymes had been analyzed using their methods. Stein died in Manhattan on February 2, 1980.
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