of bacteriophage T4 were instrumental in defining the nature of both messenger RNA and the genetic code. The short-lived nature of bacterial RNAs, together with the highly complex nature of the cellular mRNA population, made the biochemical isolation of mRNA very challenging. This problem was overcome in the 1960s by the use of reticulocytes in vertebrates, which produce large quantities of mRNA that are highly enriched in RNA encoding alpha- and beta-globin (the two major protein chains of hemoglobin). The first direct experimental evidence for the existence of mRNA was provided by such a hemoglobin synthesizing system. Ribosomes make proteins In the 1950s, results of labeling experiments in rat liver showed that radioactive amino acids were found to be associated with "microsomes" (later redefined as ribosomes) very rapidly after administration, and before they became widely incorporated into cellular proteins. Ribosomes were first visualized using electron microscopy, and their ribonucleoprotein components were identified by biophysical methods, chiefly sedimentation analysis within ultracentrifuges capable of generating very high accelerations (equivalent to hundreds of thousands times gravity). Polysomes (multiple ribosomes moving along a single mRNA molecule) were identified in the early 1960s, and their study led to an understanding of how ribosomes proceed to read the mRNA in a 5′ to 3′ direction, processively generating proteins as they do so. Transfer RNA (tRNA) is the physical link between RNA and protein Biochemical fractionation experiments showed that radioactive amino acids were rapidly incorporated into small RNA molecules that remained soluble under conditions where larger RNA-containing particles would precipitate. These molecules were termed soluble (sRNA) and were later renamed transfer RNA (tRNA). Subsequent studies showed that (i) every cell has multiple species of tRNA, each of which is associated with a single specific amino acid, (ii) that there are a matching set of enzymes responsible for linking tRNAs with the correct amino acids, and (iii) that tRNA anticodon sequences form a specific decoding interaction with mRNA codons. The genetic code is solved The genetic code consists of the translation of particular nucleotide sequences in mRNA to specific amino acid sequences in proteins (polypeptides). The ability to work out the genetic code emerged from the convergence of three different areas of study--(i) new methods to generate synthetic RNA molecules of defined composition to serve as artificial mRNAs, (ii) development of in vitro translation systems that could be used to translate the synthetic mRNAs into protein, and (iii)