A stop codon called amber got its name from a friend's German surname
Life's instruction manual fits in a 64-entry table. Each three-letter word of DNA or RNA names one amino acid or says stop, and nearly every organism reads the same table. Cracking it took a dining club of scientists, a stretch of pure uracil and, lately, bacteria rebuilt to use fewer words.
Cells build proteins by reading messenger RNA three bases at a time. Each triplet, or codon, is matched by a transfer RNA carrying one amino acid, and the ribosome strings them together. Four bases taken three at a time give 64 combinations for 20 standard amino acids, so most amino acids have several codons. Translation usually begins at AUG, which codes for methionine, and ends at one of three stop codons, where no transfer RNA fits and a release factor frees the finished chain.
After the double helix was described in 1953, physicist George Gamow proposed that triplets of bases must spell out amino acids. In 1954 he founded the RNA Tie Club, capped at 20 members for the amino acids plus four honorary ones for the bases. Francis Crick circulated a typed note to the club in January 1955 arguing that an adaptor molecule links codons to amino acids; that adaptor turned out to be transfer RNA. Crick, Brenner and colleagues later showed experimentally that codons are three bases long.
The first word was read in 1961. Marshall Nirenberg and Heinrich Matthaei fed a cell-free system an RNA made only of uracil and got a chain made only of phenylalanine, so UUU meant phenylalanine. Severo Ochoa's lab matched AAA to lysine and CCC to proline, Nirenberg and Philip Leder identified 54 of the 64 codons, and Har Gobind Khorana filled in the rest. Khorana, Nirenberg and Robert Holley, who solved the structure of transfer RNA, shared the 1968 Nobel Prize. Richard Epstein and Charles Steinberg named the first stop codon amber after their friend Harris Bernstein, then kept the colour theme with ochre and opal.
Synthetic biologists now rewrite the table. Since 2001 about 40 non-natural amino acids have been built into proteins. A bacterium with two artificial bases, X and Y, survived cell division in 2016, and in 2019 a strain of E. coli called Syn61 lived on a synthetic genome using only 61 codons, growing 1.6 times slower than normal. A 2025 strain, Syn57, dropped seven codons.
Source: Genetic code
