Answer:
Before the genetic code could be deciphered, before scientists could understand the process by which deoxyribonucleic acid (DNA) directed the synthesis of proteins, they had to resolve a final mystery: as Francis Crick and other researchers insisted, there must be a messenger to transmit genetic information from the cell nucleus to the cytoplasm, a messenger that was almost certainly made of ribonucleic acid (RNA). But what was its exact nature? Scientists had found notable amounts of RNA at the ribosome, the site of protein synthesis in the cytoplasm, and had assumed that this RNA was the postulated messenger. Each ribosome, according to this assumption, synthesized just one protein.
However, the assumption that ribosomal RNA (rRNA) was the messenger conflicted with other findings, namely that the main sections of rRNA occurred in only two lengths, whereas the polypeptide chains for which this RNA supposedly coded differed greatly in length; and secondly, that the relative amounts of the bases in rRNA were fairly constant, whereas their relative amounts in DNA varied widely from species to species. (The sequence of the bases in rRNA, as opposed to the relative amounts of its bases, would not be known for several more years.) Moreover, Arthur Pardee, François Jacob, and Jacques Monod in their famous "PaJaMo-experiment" had produced evidence that protein synthesis commenced soon after the introduction of a gene into a cell and that it proceeded at a fast, steady rate. By contrast, the theory that ribosomal RNA was the messenger predicted that protein synthesis would start up gradually, as the newly-introduced gene first had to produce the ribosomes at which protein synthesis was to occur.
If ribosomal RNA could not be the messenger, then what was? The question was resolved during a decisive meeting at King's College, Cambridge, on Good Friday, 1960, between Jacob, Sydney Brenner, Crick, and a handful of other researchers. A few years earlier, in 1956, two scientists working with a virus that infected a bacterium found in the bacterium small amounts of a form of ribonucleic acid (RNA) that had the same base composition (the same proportion in the amount of bases) as the DNA of the virus. Their finding and its significance had remained unexplained. During the meeting, Brenner had the sudden insight that this form of RNA must be the messenger because it replicated the base composition of the virus, not of the infected bacterium or its ribosomes, where virus-directed synthesis of proteins was unfolding. Messenger RNA (mRNA) was found in such small amounts that it had previously eluded detection because it was needed only for short periods of time during protein synthesis. It then degraded, to be used again in making a copy of another stretch of DNA. Brenner and the others concluded that the ribosome was just an inert reading head that could synthesize any type of protein while it traveled along the messenger RNA, reading off the bases in sequence.
With the basic concepts of genetic control of protein synthesis in place, what remained to be explained was how the genetic code worked, that is, how genetic information was transcribed from DNA to messenger RNA to protein. In an article published in Nature on December 30, 1961, Crick, Brenner, and their team described how, by inducing successive mutations in a virus that attacks the bacterium Escherichia Coli, they obtained evidence that the chemical code embodied in a gene consisted of groups of three bases which do not overlap, or share bases. The mutants studied were acridine mutants, meaning they had been exposed to the potent mutagen proflavine, a bright yellow dye derived from the coal tar chemical acridine. As Crick correctly surmised, acridines slip in and out between the bases of the virus RNA (the virus they studied was of RNA, not DNA), leading to the insertion or deletion of a base on the complementary chain during gene replication. Such insertion or deletion of a base in the viral RNA led to a "phase shift": given that, according to the sequence hypothesis, the sequence of the bases was to be read in linear fashion, from a fixed starting point and in one direction, the addition or deletion of a base would throw the reading of the base sequence out of step (out of phase) from the point of mutation onward. Consequently, proteins synthesized from viral RNA past the point of mutation were deformed, and could not perform their usual functions; the virus the team worked with was rendered less infectious, as could be determined by observing the bacterial cultures on which it preyed in the Petri dish.