Robert William Holley

1922-1993

American Biochemist

In 1968 Robert W. Holley shared the Nobel Prize in Medicine or Physiology with Har Gobind Khorana (1922- ) and Marshall W. Nirenberg (1927- ) "for their interpretation of the genetic code and its function in protein synthesis." Holley's work provided insight into the mechanism the cell uses to translate the information in the genetic code into essential proteins. Holley was one of the discoverers of the special type of nucleic acid called transfer-RNA. Having developed techniques for determining the structure of nucleic acids, Holley isolated alanine transfer RNA and determined the total sequence of nucleotides in this polynucleotide chain. This work represented the first determination of the complete chemical structure of a biologically active nucleic acid.

Holley was born in Urbana, Illinois, but he also lived in California and Idaho during his youth and developed a love of the outdoors and an interest in living things. Both of his parents were teachers. He majored in chemistry at the University of Illinois and received his B. A. degree in 1942. His wife, Anne Dworkin, was a chemist and mathematics teacher. In 1947 he was awarded the Ph.D. degree in organic chemistry from Cornell University. World War II interrupted his graduate work. From 1944 to 1946, he carried out research for the United States Office of Research and Development at Cornell University Medical College, where he participated in the first chemical synthesis of penicillin. Holley spent two years as an instructor and American Chemical Society Postdoctoral Fellow at Washington State University before returning to Cornell in 1948 as assistant professor of organic chemistry at the Geneva Experiment Station. During a sabbatical year (1955-1956), he was a Guggenheim Memorial Fellow at the California Institute of Technology. After returning to Cornell, he took the position of Research Chemist at the United States Department of Agriculture's Plant, Soil, and Nutrition Laboratory at Cornell. He was Professor of Biochemistry and Molecular Biology at Cornell until 1966. Although he maintained an affiliation with Cornell, he moved to the Salk Institute for Biological Studies in La Jolla, California, in 1967, where he became a resident fellow and professor. He also held the position of Adjunct Professor at the University of California at San Diego.

Holley's initial research topics concerned the organic chemistry of natural products and gradually turned to more biological subjects, including work on amino acids and peptides, and eventually work on the biosynthesis of proteins. Holley did his landmark RNA work while at Cornell University. His classic paper on deciphering the genetic code for RNA, "Sequences in Yeast Alanine Transfer Ribonucleic Acid," appeared in the Journal of Biological Chemistry in 1965. During his studies of the biosynthesis of proteins, Holley discovered alanine transfer RNA. Isolating and determining the structure of this RNA with the available techniques took about 10 years. The laborious work of sequencing the polynucleotide sequence of the alanine transfer RNA was completed in 1964. The nucleotide sequence of alanine transfer RNA was the first nucleic acid for which a complete structure had been established. Moreover, Holley's work helped explain how transfer RNAs are involved in reading the genetic code and transforming the information in the nucleic acid of the gene into the amino acids of the proteins.

In the 1970s, Holley became more involved in studies of the factors that control cell division in mammalian cells. He concluded that the factors that controlled growth and development were probably polypeptide hormones, hormone-like substances, and various low molecular weight nutrients.

In addition to the Nobel Prize, Holley won many other honors, including the Albert Lasker Award in Basic Medical Research, the Distinguished Service Award of the U. S. Department of Agriculture, and the U. S. Steel Foundation Award in Molecular Biology of the National Academy of Sciences. Holley was a member of the National Academy of Sciences, the American Academy of Arts and Sciences, the American Association for the Advancement of Science, the American Society of Biological Chemists, and the American Chemical Society.

LOIS N. MAGNER