Max Bergmann (February 12, 1886-November 7, 1944) was a biochemist, whose research proved key for the study of biochemical processes. His work on peptide synthesis and protein splitting provided a starting point for modern protein chemistry and the study of enzyme-substrate interactions. He is most noted for developing the carbobenzoxy protecting group, for the synthesis of oligopeptides, using any amino acid in any sequence. He co-authored with his colleague Joseph S. Fruton (1912-2007, APS 1967) several reviews in protein and enzyme chemistry, notably “Proteolytic Enzymes,” in the Annual Review of Biochemistry 10 (1941): 31-46 and “The Specificity of Proteinases,” in Advances in Enzymology 1 (1941): 63-98.
Bergmann was born in Fürth, Germany, the son of a coal merchant named Solomon Bergmann and his wife Rosalie Stettauer. He entered the University of Munich, initially interested in botany, but shifted to chemistry, after being convinced that biological questions could only be answered by the methods of organic chemistry. He received a bachelor’s degree in 1907, and afterward became a student of Emil Fischer (1838-1914, APS 1909), the foremost protein and carbohydrate chemist of the day at the University of Berlin. In 1911 Bergmann received a Ph.D. with a dissertation on acyl polysulfides and became Fischer’s research assistant. In 1912 Bergmann married Emmy Miriam Grunwald with whom he had two children. The marriage ended in divorce, and he remarried Martha Suter in 1926. During World War I Bergmann was exempted from military service because of his research work with Fischer. While working with Fischer, Bergmann made important contributions to carbohydrate, lipid, tannin and amino acid chemistry, developing new methods for the preparation of α-monoglycerides. In 1920 Bergmann was appointed Privatdozent at the University of Berlin and head of the chemistry department at the Kaiser Wilhelm Institute for Textile Research.
Bergmann left the University of Berlin in 1921 to become the director of the new Kaiser Wilhelm Institute for Leather Research and Professor of chemistry at the Dresden Technical University. At Dresden, Bergmann created one of the world’s leading laboratories for the study of protein chemistry. After Adolf Hitler’s rise to power, Bergmann, a Jew, emigrated to the United States. From 1934 until his death Bergmann was affiliated with the Rockefeller Institute for Medical Research in New York.
Bergmann represents the tradition of German organic chemistry applied to biological problems. Working with his mentor Fischer, who sought effective methods to separate and identify amino acids, and who identified the peptide bond as the structure that connects amino acids, Bergmann made many basic contributions to protein and amino acid chemistry. In Dresden he extended Fischer’s work of separating and identifying the amino acid constituents of proteins. In order to establish the conjecture of some protein chemists that proteins were, in fact, polypeptides, containing thousands of amino acids, Bergmann developed new methods of peptide synthesis. The most important discovery came in 1932, when he and his colleague Leonidas Zervas created the carbobenzoxy method allowing them to use any amino acid in any sequence to produce peptides and polypeptides that closely resembled naturally occurring proteins.
Bergmann continued this work in New York at the Rockefeller Institute, stressing two new lines of research: (1) expanding the carbobenzoxy method to form peptides that could serve as substrates for protein-splitting enzymes, and (2) unraveling the total structure of proteins. After becoming head of the chemistry laboratory at the Rockefeller Institute in 1937, Bergmann recruited several talented biochemists. Along with his colleague Joseph Fruton, he discovered the first synthetic peptide substrates for which several enzymes were catalysts. When they demonstrated that the enzyme pepsin was able to catalyze the hydrolysis of synthetic peptides, they implicated the peptide bond in protein structure, but also provided the first clear evidence that specific enzymes split peptides at exact linkages in the chain. Their discovery cleared the path for study of how enzymes act as catalysts for every biological function.
Bergmann’s methods of analysis and synthesis proved incapable of solving the riddle of protein structure. He applied methods for separation and quantitative analysis to every amino acid in a protein in an attempt to establish their sequence in the polypeptide chain. In 1938 he proposed a theory of the systematic recurrence in the location of every amino acid residue in the peptide chain of a protein. However, his hypothesis proved an oversimplification. Two biochemists in his working group, Standford Moore and William Stein, showed him that the analytical data did not support his “periodic theory,” and Bergmann was forced to abandon it. Moore and Stein later collaborated in developing novel methods for quantitative analysis of amino acids in protein hydrolysates, methods they perfected after World War II. By 1949 it was possible to determine the order of the links of each amino acid in a protein. The Englishman Frederick Sanger was the first to establish the complete amino acid sequence in a protein, the hormone insulin. Moore and Stein followed by identifying the sequence of a more complex protein, the enzyme ribonuclease.
Bergman died of cancer in New York City on November 7, 1944. His mastery of peptide synthesis and protein splitting constituted the beginnings of modern protein chemistry. Bringing to the United States a background in German organic chemistry, he laid the foundations for the work of others, who would fulfill Bergmann’s goal of understanding and mapping the molecular structure of proteins and enzymes. His research colleagues found him a supportive leader and collaborator. He coauthored a number of publications with other members of his research group.
From the guide to the Max Bergmann papers, [ca. 1930]-1945, 1930-1945, (American Philosophical Society)
