Contributions of Organic Chemists to Biochemistry: Louis F. Fieser, Mary Fieser, and Max Tishler
Year: 2003
Type: article
Abstract: VITAMIN K ACTIVITY AND STRUCTUREJournal of Biological ChemistryVol. 137Issue 2Preview Full-Text PDF Open Access Vitamin K Activity and Structure (Fieser, L. F., Tishler, M., and Sampson, W. L. (1941) J. Biol. Chem. 137, 659–692) This paper was selected as a JBC Classic because it represents the research and teaching accomplishments of giants of organic chemistry and the application of synthetic organic chemistry to biochemistry. The work is a classic structure-function analysis of a class of compounds for biological activity. Using a bioassay for the antihemorrhagic activity of vitamin K, the authors screened 79 naphthoquinones either synthesized for this purpose or previously studied to determine which structural elements are essential for activity. Louis Frederick Fieser (1899–1977) was born in Columbus, Ohio. After completing high school in Columbus, he attended Williams College graduating in 1920 with a degree in chemistry. He attended graduate school at Harvard and completed his thesis on the oxidation-reduction potentials of quinones with James Bryant Conant, who later became President of Harvard. After a fellowship year in Europe, he assumed his first teaching position at Bryn Mawr College. He served there until 1930 when he returned to Harvard as an assistant professor and remained until he became emeritus in 1968 (1Gates M. Biographical memoir for Louis Frederick Fieser..Biogr. Mem. Natl. Acad. Sci. 1994; 65: 161-175Google Scholar). 1The biographical information for Louis Fieser is from Ref. 1Gates M. Biographical memoir for Louis Frederick Fieser..Biogr. Mem. Natl. Acad. Sci. 1994; 65: 161-175Google Scholar.1The biographical information for Louis Fieser is from Ref. 1Gates M. Biographical memoir for Louis Frederick Fieser..Biogr. Mem. Natl. Acad. Sci. 1994; 65: 161-175Google Scholar. While at Bryn Mawr, Fieser met Mary Peters (1909–1997), who was a member of his second class. After graduating in 1930, she entered Radcliffe College for graduate study in chemistry with Fieser who had moved to Harvard the same year. Her enrollment at Radcliffe was necessary in order for her to take chemistry classes at Harvard because Harvard did not accept women. Although she took the same classes from Harvard faculty as Harvard men, women were not allowed to take the classes at the same time or in the same building as the men. Therefore the Harvard faculty would give one lecture to men and the same lecture to women in a different building (2Biographical Snapshots of Famous Women and Minority Chemists. Journal of Chemical Education Online (http://jchemed.chem.wisc.edu/JCEWWW/Features/eChemists/Bios/fieser.html)Google Scholar). Mary and Louis Fieser were married in 1932 and began a remarkable research, teaching, and literary collaboration which lasted until Louis' death in 1977. Together they published 35 research papers, 8 books, and the important series Reagents for Organic Synthesis. Their textbooks Organic Chemistry, Textbook of Organic Chemistry, Introduction to Organic Chemistry, Basic Organic Chemistry, Advanced Organic Chemistry, Topics in Organic Chemistry, and Current Topics in Organic Chemistry introduced generations of students to the study of organic chemistry. The first volume of their series, Reagents for Organic Synthesis, was published in 1967, and Volume 15 was published in 1990. Seven volumes were published before Louis' death in 1977; the remainder were prepared by Mary often with a collaborator. This series is the most important of the Fiesers' publications and has been indispensable for all practicing organic chemists. In 1936, Mary received her masters degree from Radcliffe and decided not to pursue doctoral studies. She never was granted a salary by Harvard University but was given the title, Research Fellow of Chemistry, 29 years after she had begun her work there. In 1996, Mary dedicated the Louis and Mary Fieser Laboratory for Undergraduate Organic Chemistry at Harvard. Louis' research was varied. His interest in quinones, exhibited first in his thesis work, led to the studies and synthesis of vitamin K (3Fieser L.F. The synthesis of vitamin K..Science. 1940; 91: 31Crossref PubMed Google Scholar) plus numerous structural variants, the subject of this JBC Classic. He was a virtuoso experimentalist, who took particular pride in devising simple, practical, and ingenious solutions to experimental problems. There was an annual contest between Fieser and students in his class based on the preparation of the yellow dye Martius Yellow from 1-naphthol. The criteria were judged on speed and purity of the product. Fieser always won but also was always disqualified on some technicality. During World War II, Fieser devoted much of his research effort to the synthesis and screening of quinones as antimalarial agents. More than 300 compounds were synthesized and tested, and although some appeared promising, none proved to be clinically effective. Fieser was also well known as a dedicated and gifted teacher. For many years, he taught Chemistry 2, later Chemistry 20, the introductory course in organic chemistry at Harvard. His lab manuals were meticulous. He was also famous for dramatic lab demonstrations including a lesson on how not to do a recrystallization, which resulted in his being covered with decolorizing charcoal to the delight of his students. He used his classes also to test syntheses before publication and to engage his students in research. In one JBC paper (4Fieser L.F. Convenient procedure for the preparation of antihemorrhagic compounds..J. Biol. Chem. 1940; 133: 391-396Abstract Full Text PDF Google Scholar), Fieser recorded that “all procedures were submitted for trial to a group of students in a course in elementary organic chemistry with fully successful results.” Fieser received many honors for his research and teaching including election to the National Academy of Sciences (1940) and an award from the American Chemical Society as a “Giant in Chemical Education” (1976). In his honor, the June 1965 issue of the Journal of Organic Chemistry published 112 papers by his former students and colleagues. He also received many honorary degrees. Max Tishler (1906–1989), a co-author of this JBC Classic, was another legendary organic chemist, whose career path was rather different from Fieser's and took him to industry rather than industry. Born in Boston, he was the fifth of six children in a family that had been deserted by their father when Max was 5 years old. As he grew up, he shared the burden of supporting the family including working as a pharmacist's assistant. This experience sparked his interest in chemistry and desire to make a contribution to health care, which endured throughout his life. An outstanding high school record earned him a scholarship to Tufts College, now Tufts University, and he graduated magna cum laude with a B.S. in chemistry in 1928. He enrolled in graduate school at Harvard and received a Ph.D. degree in organic chemistry in 1934 for his thesis work with Elmer P. Kohler. He was also influenced by James Bryant Conant who, together with Kohler, helped him to get his first job at Merck in 1937, a time when academic positions were scarce (5Sarett L.H. Roche C. Biographical memoir for Max Tishler..Biogr. Mem. Natl. Acad. Sci. 1995; 66: 353-369www.nap.edu/readingroom/books/biomems/mtishler.htmlPubMed Google Scholar). 2The biographical information for Max Tishler is from Ref. 5Sarett L.H. Roche C. Biographical memoir for Max Tishler..Biogr. Mem. Natl. Acad. Sci. 1995; 66: 353-369www.nap.edu/readingroom/books/biomems/mtishler.htmlPubMed Google Scholar.2The biographical information for Max Tishler is from Ref. 5Sarett L.H. Roche C. Biographical memoir for Max Tishler..Biogr. Mem. Natl. Acad. Sci. 1995; 66: 353-369www.nap.edu/readingroom/books/biomems/mtishler.htmlPubMed Google Scholar. When Tishler joined Merck in 1937, it was a relatively small company making fine chemicals in Rahway, New Jersey. George W. Merck, son of the founder, wanted to use the firm's sales base in commodity chemicals to build a more innovative organization for the creation of therapeutic chemicals. He initiated an expansion of the laboratories and introduced basic research. He recruited Karl Folkers from Yale who had expertise in the isolation of natural products that were medically useful such as hormones and vitamins. They both recognized the importance of developing manufacturing techniques to expand the milligram quantities prepared in a research laboratory to the relatively massive amounts necessary for medicinal purposes. Max Tishler's first job at Merck was as a product development chemist. His first production-scale product was riboflavin, and Merck was able to produce quantities sufficient for enriching white bread. His biggest challenge was the production of cortisone. During World War II there was enormous pressure from the medical community and from the government to produce cortisone on a large scale. Tishler eventually succeeded in establishing the most complex manufacturing process ever developed by the pharmaceutical industry and created a supply of cortisone sufficient for medical use. Many more successes followed, and Tishler rose through the ranks to become the first president of the Merck Sharp & Dohme Research Laboratory Division of Merck & Co. Inc. Among numerous products developed under Tishler's leadership were ascorbic acid, riboflavin, cortisone, thiamin, pyridoxine, pantothenic acid, nicotinamide, methionine, threonine, tryptophan, actinomycin D, vitamin B12, streptomycin, and penicillin. In 1969, Tishler was appointed Senior Vice-President for Science and Technology, a position that removed him from interactions with scientists, and in 1970, 18 months before his mandatory retirement at Merck, he accepted a position as Professor of Chemistry at Wesleyan University. To Wesleyan, Tishler brought the same energy and leadership that had characterized his tenure at Merck, and at the age of 64, he launched a new career. He helped lead the effort to establish a Ph.D. program in chemistry. He supervised graduate students and was a model mentor. He became University Professor of the Sciences and chairman of the chemistry department. He remained active in all phases of departmental life even after becoming emeritus in 1975 and continued to do so until a few weeks before his death. Tishler received many honors during his career. He was elected to the National Academy of Sciences (1954) and received the National Medal of Science from Ronald Reagan (1987).
Source: Journal of Biological Chemistry
Language: English
Subfield: History and Philosophy of Science
Field: Arts and Humanities
Domain: Social Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1538930799