The study of the primary structure of nucleic acids, i. e. , the determination of the nucleotide sequence in ribosomal, transfer, and messenger types of RNA and in DNA, is an essential preliminary to the attempt to correlate the structures of these compounds with their functions. This is one of the most urgent problems in molecular biology, for until it is solved it is im possible to understand fully the mechanisms of fundamental living processes. Research has naturally tended to concentrate on the nucleic acids of smallest molecular weight, namely the transfer RNAs, and tremendous progress has been made in recent years in the unraveling of their structure. In 1958-1959, when structural investigation was still in its infancy, it was even doubted whether the structure of any transfer RNA could be deter mined. No methods of isolating homogeneous preparations were available, and it was uncertain whether the very slight physical and chemical differences between tRNAs of different specificity would be sufficient to allow successful fractionation. When the first enriched preparations were obtained, there arose the problem of whether it was possible to determine the nucleotide sequence having regard to the limited number of heterogeneous structural elements present in tRNA. These doubts were resolved in 1965, when the structure of the first nucleic acid, alanine-specific transfer RNA, was unraveled in Holley's laboratory.
