Early experiments on the genetic code

In the $1950$‍’s, scientists knew that DNA provided the genetic code for life. However the mechanism of how DNA coded for the the expression of proteins remained unknown. Marshall Nirenberg, who was awarded the Nobel Prize in Physiology or Medicine in $1968$‍ for his research, sought to figure this out. Nirenberg, along with Heinrich Matthaei, designed an experiment to determine how proteins could be synthesized from DNA. The experimental set-up used E. coli cell extract, which contained all of the components needed for protein synthesis in a cell-free system. To this, they added a synthetic RNA strand made up of only uracil and DNase to remove other DNA in the system. They then prepared a test tube that contained a single C${}^{14}$‍ radioactively labeled amino acid and nineteen unlabeled amino acids. This set-up was repeated nineteen times, with each test tube containing a different labeled amino acid mixed with the other nineteen unlabeled amino acids.

When they ran the experiment, they found the results shown in Table 1.

Table 1. Radiolabeled protein production with addition of poly-uracil RNA

Adapted from: Nirenberg, M. W. & Matthaei, M. (1961). The Dependence of Cell-Free Protein Synthesis in E. coli Upon Naturally Occurring or Synthetic Polyribonucleotides. PNAS, 47, 1588-1602.

This same experiment was repeated with poly-adenine and poly-cytosine RNA. This was the first of many steps in deciphering the codons of the genetic code. By $1966$‍ Nirenberg announced that he had deciphered all of the codons for the twenty amino acids.