Anfinsen, Christian Boehmer

(b. 26 March 1916 in Monessen, Pennsylvania; d. 14 May 1995 in Randallstown, Maryland), biochemist who shared the 1972 Nobel Prize in chemistry with Sanford Moore and William Stein for his discovery of the connection between the primary and tertiary structure of enzymes.

Anfinsen was born in a small town near Pittsburgh to Christian Anfinsen, an engineer and immigrant from Norway, and Sophie Rasmussen, a homemaker also of Norwegian heritage. After attending local schools, Anfinsen received a bachelor’s degree at Swarthmore College in 1937 and a master’s degree at the University of Pennsylvania in 1939. After completing his master’s degree, he received a fellowship from the American Scandinavian Foundation to spend a year at the Carlsberg Laboratory in Copenhagen, Denmark. Returning to the United States in 1940, he entered Harvard University, where he earned his doctorate in biochemistry in 1943. On 29 November 1941 he married Florence Bernice Kenenger, with whom he had three children.

In 1943 Anfinsen became an assistant professor of biological chemistry at Harvard. Taking a leave from Harvard from 1944 to 1946, he worked in the U.S. Office of Scientific Research and Development, then in the biochemical division of the Medical Nobel Institute in Sweden as an American Cancer Society senior fellow. In 1946 he returned to Harvard to take a position as associate professor, remaining until 1950. Anfinsen joined the staff of the National Institutes of Health in Bethesda, Maryland, in 1950 and until 1962 was the director of the Laboratory of Cellular Physiology and Metabolism. From 1962 to 1982 he headed the Laboratory of Chemical Biology at the National Institute of Arthritis, Metabolism, and Digestive Diseases in Bethesda, Maryland.

Anfinsen received the Rockefeller Foundation Public Service Award in 1954 and a Guggenheim fellowship for research at the Weizmann Institute of Science in Israel in 1958. Between 1962 and 1982 he received several honorary degrees and held professorships at several universities. He was a member of the Royal Danish Academy, president of the American Society of Biological Chemistry, a member of the Board of Governors of the Weizmann Institute of Science, a member of the U.S. National Academy of Sciences, and a member of the American Academy of Arts and Sciences. He was an editor of the magazine Advances in Protein Chemistry and served on the editorial boards of the Journal of Biological Chemistry, Biopolymers, and the Proceedings of the National Academy of Sciences.

Anfinsen’s primary research was devoted to studying the structure and function of enzymes, the proteins that promote biochemical reactions. He was the quintessential protein chemist, a man acutely aware of both the chemical and biological sides of the field. He began an experimental study of protein biosynthesis in the late 1940s, before the structure of DNA was known. He later diversified his activities in a more chemical direction in the mid-1950s, when a large supply of the bovine enzyme pancreatic ribonuclease became available. In the late 1960s he studied the structure and function of many proteins with a particular interest in nuclease, the enzyme that breaks down nucleic acids. His research determined how a particular set of amino acids configure in a way that results in the active form of the enzyme.

Anfinsen shared the Nobel Prize in chemistry with San-ford Moore and William Stein in 1972 while Anfinsen was chief of the Laboratory of Chemical Biology at the National Institutes of Health. The prize was awarded for pioneering work relating to the structure and biological function of the enzyme ribonuclease. Stein and Moore concentrated on the sequencing of the ribonuclease chain, only the second complete sequence of a protein yet determined at that time. Anfinsen and his team concentrated on the effects of the enzyme’s structure on its catalytic properties. He ascertained how the ribonuclease molecule folds to form the characteristic three-dimensional structure that is compatible with its function. In other words, he discovered the connection between the primary and tertiary structures of enzymes.

To accomplish this Anfinsen observed a complete ribonuclease molecule under a variety of conditions, establishing that the tertiary structure of active ribonuclease arises because it is the most stable arrangement of its amino acids under normal physiological conditions. One modification he experimented with was the reduction of the four disulfide bonds in the native molecule to eight sulphydryl groups, with the understanding that sulphydryl groups can be reoxidized back to the disulphide form. Anfinsen left the reduced enzyme solution out in the air overnight. By the following day almost all of the catalytic activity had returned, meaning that the protein had reformed its native structure unaided. He concluded that all the information necessary to conserve the randomly coiled peptide chain into its unique, biologically active structure was contained in the sequence of amino-acids residue in the chain. This was the final answer to the last step in protein biosynthesis. Anfinsen’s result was confirmed later in dozens of papers from his own laboratories and in thousands of papers from other laboratories.

Anfinsen authored some 200 original scientific articles. His seminal work, The Molecular Basis of Evolution, published in 1959, laid out the general outline and basic requirements for the complexity of the evolutionary process. A tall and pleasant-looking man, he divorced his first wife in 1978 and in 1979 married Libby Esther Schulman. With that marriage, he became stepfather to three sons and one daughter.

Anfinsen was a professor of biology at Johns Hopkins University from 1982 until his death. During his later years at Johns Hopkins he began experimenting with proteins of hyperthermophillic (extreme heat-loving) bacteria taken from hydrothermal vents on the floors of the Mediterranean Sea and the Pacific Ocean. He died at the age of seventy-nine of an apparent heart attack at the Northwest Hospital Center in Randallstown.

The work of Anfinsen, Moore, and Stein laid a pathway for future investigations in protein chemistry and opened the door for major breakthroughs involving hundreds of enzymes. Their conclusions have been used in research on various diseases, including cancer, and have provided a prototype for many studies.

For brief biological information on Anfinsen see American Men and Women of Science (19th ed., 1995–1996. Emily J. McMurray, ed., Notable Twentieth-Century Scientists, vol. 1 (1995), includes details on his research work; and Charles R. Cornell, ed., Biography Index: A Cumulative Index to Biographical Material in Booths and Magazines, September 1995 to August 1996 (1996), provides a brief summary of Anfinsen’s life and work. An obituary is in the New York Times (16 May 1995) and Nature (6 July 1995).

Maria Pacheco