Nirenberg's Genetic Code Chart, 1961-66

On May 27, 1961, Heinrich Matthaei, a postdoc working with NIH scientist Marshal Nirenberg, placed synthetic polyuracil RNA into 20 test tubes to see what it would produce. Each tube contained cytoplasmic extract from Escherichia coli and a specific radiolabeled amino acid. Ribosomes from the tube containing labeled phenylalanine came back 'hot,' and the world was a step closer to understanding the genetic code.

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Courtesy of Terry Sharrer

Three months later, Nirenberg reported their findings in Moscow and the race began in earnest. Though it took several years, Nirenberg and others deciphered the meaning of all 64 triplet codons. Nirenberg and Matthaei kept track of the progress on this 15" x 48" chart pieced together from scraps of graph paper. The 20 radioactive aminoacyl-tRNA preparations are listed across the top, and the 64 RNA triplets are on the vertical axis. The pencil notations in this matrix corresponded to amount of labeled aminoacyl-tRNA that bound ribosomes during expression.

By 1966 the chart had been completed. Two years later, Nirenberg, Robert Holley (who discovered and purified transfer RNA), and Gobind Khorana (who pioneered chemical nucleotide synthesis), shared the Nobel Prize "for their interpretation of the genetic code and its function in protein synthesis."

These efforts overcame a major hurdle, effectively opening biology to molecular study. For Nirenberg and the other code-breakers, concerns arose almost immediately as to how this knowledge might be used, for example in tampering with life (see "Cracking the Clone"), or creating novel pathogens.¹