William Howard Stein (June 25, 1911 – February 2, 1980) was an Americanbiochemist who collaborated in the determination of theribonuclease sequence, as well as how its structure relates tocatalytic activity, earning aNobel Prize in Chemistry in 1972 for his work.[2] Stein was also involved in the invention of the automaticamino acid analyzer, an advancement inchromatography that opened the door to modern methods of chromatography, such as liquid chromatography andgas chromatography.[3]
William H. Stein was born on June 25, 1911 inNew York City[4] into aJewish family.[5] His father, Fred M. Stein, was a businessman who retired early to support local New York health organizations.[4] His mother, Beatrice Borg Stein, was a children's rights activist who developed afterschool activities.[4][6] Staunch advocates for the welfare of society, Stein's parents fostered his interests in the life sciences from a young age.[4] As a child, Stein attended the recently established "progressive" Lincoln School which was sponsored by theTeachers College of Columbia University; there, he was able to explore the natural sciences through field trips and science projects.[4] At the age of sixteen, Stein was transferred to thePhillips Exeter Academy inNew England to prepare for higher education.[4]
In 1936, during his graduate studies at Columbia University, William H. Stein married Phoebe Hockstader.[4] They had three sons together: William H. Stein, Jr., David F. Stein, and Robert J. Stein. Stein lived with his family inNew York the rest of his life—mainly inManhattan and briefly inScarsdale, New York.[4]
William H. Stein began his higher education as a chemistry major atHarvard University in 1929.[4] He spent one year as a graduate student at Harvard University before transferring to the Department of Biological Chemistry at the College of Physicians and Surgeons,Columbia University, in 1934 to focus onbiochemistry.[4]Hans Thatcher Clarke, the chairman of the department at the time, was collecting many talented graduate students who would become the distinguished biochemists of the early twentieth century.[4][6] In 1937, Stein completed his thesis on the amino acid composition ofelastin, earning his Ph.D.[4] Stein was introduced to potassium trioxalatochromate and ammonium rhodanilate byMax Bergmann, a Jewish-German biochemist who fled to the United States in 1934 under threat of Nazi occupation and worked in a laboratory at theRockefeller Institute.[6] He used these two precipitating agents to isolate the amino acidsglycine andproline, respectively, for his research on elastin.[6] With the conclusion of his academic career, Stein went on to work under Bergmann.[4]
William H. Stein and his wife traveled around the world and hosted many prominent scientists in their own home in New York City throughout his scientific career.[4] In addition to Stein's long-term professorship at Rockefeller Institute, he served as a visiting professor to theUniversity of Chicago in 1961 andHarvard University in 1964.[6] Stein also lectured at theWashington University in St. Louis andHaverford College.[7]
In 1969, Stein experienced sudden paralysis, diagnosed asGuillain–Barré syndrome, after developing a fever several days prior during a symposium inCopenhagen.[4] Despite remainingquadriplegic the rest of his life, Stein's colleagues alleged that his spirit and sense of humor endured.[4] He continued to be a guiding presence at the Rockefeller Institute to his younger colleagues and their work on the study ofRNase.[4] At the age of sixty-eight, Stein experienced unexpected heart failure.[4] William H. Stein died February 2, 1980 in New York City.[4]
Following the completion of his formal education, Stein became a researcher under Bergmann at Rockefeller Institute, where much of his most important work was done.[7]Stanford Moore joined Bergmann's lab in 1939, where he and Stein began research focusing on amino acids.[8] According to Moore, "During the early years of our cooperation, Stein and I worked out a system of collaboration that lasted for a lifetime."[4] Their work in this area was disrupted with the beginning ofWorld War II, and they temporarily parted ways to aid the war efforts, Stein staying with Bergmann to research the molecular scale effect ofblister agents on the human body.[8] They began collaborating again, however, after Bergmann died in 1944 and they were given an opportunity by the Director of the Rockefeller Institute,Herbert S. Gasser, to continue Bergmann's work in amino acids.[8]
Stein and Moore developed a method to quantify and separate amino acids withcolumn chromatography, usingpotato starch as the stationary phase.[8] Thefractions, originally collected manually, were collected in their newly developed automated fraction collector, and the amount of each amino acid was determined by an adjustedcolor reaction withninhydrin.[3] They began testing other methods of separation, such asion exchange chromatography, to reduce the analysis time, as it took two weeks to analyze one protein using the starch columns.[8] Ion exchange chromatography reduced the time to 5 days during initial experiments, and eventually Stein and Moore whittled the process down even further with the help of Daryl Spackman, which resulted in the first automatic amino acid analyzer.[8] Along with their well-known work in protein sequences, this automatic amino acid analyzer was also utilized in Stein's study of amino acids in human urine[9] and blood plasma.[10]
With their success in improving the analysis time for amino acids, Stein and Moore began to determine the structure of an entire protein molecule, specifically bovine ribonuclease, in the early 1950s.[11] They determined the entire sequence of ribonuclease by 1960.[12] This sequence combined withX-ray analysis of the crystallized ribonuclease lead to the determination of the nuclease's active site.[13] Stein won a Nobel Prize in Chemistry in 1972 with Moore andChristian Boehmer Anfinsen, for their work on ribonuclease and "for their contribution to the understanding of the connection between chemical structure and catalytic activity of the ribonuclease molecule."[2]
William H. Stein received numerous honors from Columbia University and the Albert Einstein College of Medicine of Yeshiva University, including:[4][6] D.Sc.honoris causa, Columbia University (1973), D.Sc.honoris causa, Albert Einstein College of Medicine of Yeshiva University (1973), and the Award of Excellence Medal, Columbia University Graduate Faculty and Alumni Association (1973).
William H. Stein was a member of several scientific societies, including the:[6][7] National Academy of Sciences (elected to membership in 1960), American Academy of Arts and Sciences (elected to membership in 1960), American Society of Biological Chemists, Biochemical Society of London, American Chemical Society, American Association for the Advancement of Science, and Harvey Society of New York.
^abEttre LS (2008).Chapters in the evolution of chromatography. John V. Hinshaw. London: Imperial College Press. pp. 246,253–254,372–373.ISBN978-1-86094-944-9.OCLC294759403.
William Howard Stein on Nobelprize.org with the Nobel Lecture, December 11, 1972The Chemical Structures of Pancreatic Ribonuclease and Deoxyribonuclease