Cracking the Code

A chronological journey through the Atomic Age of Biology to decipher the language of life.

1954

George Gamow

The "Diamond Code" Proposal

A physicist who proposed that since there are 4 bases and 20 amino acids, the code must be read in groups of three (triplets).

Importance Provided the theoretical foundation. Although his specific overlapping model was wrong, the "Triplet" concept set the target for biologists.
1955

Severo Ochoa

Enzymatic Synthesis of RNA

Discovered Polynucleotide Phosphorylase, an enzyme that can synthesize RNA strings without a DNA template.

Importance The Tool Maker. His enzyme allowed scientists to create synthetic RNA (like Poly-U), which was the key ingredient needed for Nirenberg's experiments.
1961

Nirenberg & Matthaei

The Poly-U Experiment

They used Ochoa's enzyme to make RNA made entirely of Uracil (UUUUU). When added to a cell-free system, it produced a protein made only of Phenylalanine.

Importance The First Word Deciphered. They proved that the codon UUU codes for Phenylalanine. The code was crackable!
1961

Francis Crick

Frameshift Mutations

Working with Brenner, he inserted/deleted bases in bacteriophages. He showed that adding 1 or 2 bases destroyed the gene, but adding 3 restored it.

Importance Structural Proof. Confirmed the genetic code is indeed a Triplet code and is commaless (read continuously).
Mid 1960s

H.G. Khorana

Chemical Synthesis of Genes

Developed a method to chemically synthesize RNA molecules with defined repeating sequences (e.g., UGUGUG...).

Importance Completing the Dictionary. While Nirenberg cracked the easy homopolymers (UUU, AAA), Khorana's precise synthesis allowed them to decipher the rest of the 64 codons.