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Indeed, protein synthesis seemed almost always associated not with DNA but rather with RNA, which occurred in small, concentrated particles throughout the cytoplasm. These particles, usually associated with cellular membranes, were called ribosomes, referring to their ribonucleic acid content. RIBOSOMES AND PROTEIN SYNTHESIS Were these ribosomes then the site of protein synthesis? It was possible to show that this was true in a very straightforward way: working with bacteria (their ribosomes are easy to purify), protein synthesis was monitored by adding radioactive sulfur to a growing culture (35S ends up in the amino acids cysteine and methionine, and not in DNA or carbohydrate).

While for 25 years it had been clear the DNA contained the basic genetic information, by 1960 it was still not at all clear how that information was expressed. How did a difference in the sequence of nucleotide bases translate into the differences between an elephant and a flea? The boundaries of the problem had been roughed out even before the era of Watson-Crick DNA. It was shown that all of the enzymatic proteins that determine a cell’s physiology, morphology, and development are specifically encoded as individual genes in the chromosomes.

By using radioactivelylabeled synthetic mRNA molecules, they were able to assign specific triplets to each of the 20 amino acids. BREAKING THE CODE REQUIRED ORGANIC CHEMISTRY The key breakthrough in deciphering the genetic code came from an unexpected direction. In 1960, Marshall Nirenberg and J. H. Matthaei developed a system for synthesizing proteins in vitro. They had learned that preparation of disrupted cells soon ceased to make protein, and, in an attempt to prolong the short period during which in vitro synthesis continued, they added RNA to the preparations (rRNA, as it happens).

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how the scientists think. Twenty-One Experiments that Have Shaped Our Understanding of Genetics and Molecular Biology by George Johnson

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