Nirenberg and Matthaei experiment

Discoveries by Frederick Griffith and improved on by Oswald Avery discovered that the substance responsible for producing inheritable change in the disease-causing bacteria (Streptococcus pneumoniae) was neither a protein nor a lipid, rather deoxyribonucleic acid (DNA).

In 1953, with the help of Maurice Wilkins and Rosalind Franklin's X-ray crystallography, James Watson and Francis Crick proposed DNA is structured as a double helix.

[1] In the 1960s, one main DNA mystery scientists needed to figure out was the number of bases found in each code word, or codon, during transcription.

Seymour Benzer in the late 1950s had developed an assay using phage mutations which provided the first detailed linearly structured map of a genetic region.

[5] They correctly concluded that the code is degenerate (multiple triplets can correspond to a single amino acid) and that each nucleotide sequence is read from a specific starting point.

[6] In order to decipher this biological mystery, Nirenberg and Matthaei needed a cell-free system that would build amino acids into proteins.

Following the work of Alfred Tissieres and after a few failed attempts, they created a stable system by rupturing E. coli bacteria cells and releasing the contents of the cytoplasm.

In August 1961, at the International Congress of Biochemistry in Moscow, Nirenberg presented the poly-U experiments – first to a small group, but then at Francis Crick's urging, again to about a thousand attendees.

"[9] [12][13] Indeed, "for their interpretation of the genetic code and its function in protein synthesis," Marshall W. Nirenberg, Robert W. Holley, and Har Gobind Khorana were awarded the 1968 Nobel Prize in Physiology or Medicine.

[15] The New York Times said of Nirenberg's discovery that "the science of biology has reached a new frontier," leading to "a revolution far greater in its potential significance than the atomic or hydrogen bomb."

For example, Arne Tiselius, the 1948 Nobel Laureate in Chemistry, asserted that knowledge of the genetic code could "lead to methods of tampering with life, of creating new diseases, of controlling minds, of influencing heredity, even perhaps in certain desired directions.

Nirenberg (right) and Matthaei at the National Institutes of Health
One of Nirenberg's laboratory notebooks