Cracking the code

Painstakingly handwritten chart preserves feat of breaking DNA code

When scientists discovered DNA and its doublehelix form, they had finally identified the molecules that contain every human’s unique genetic code.

But determining how those instructions were interpreted by cells was a beast of a challenge. Scientists had to figure out how a double helix of just four building blocks could be translated into proteins, the molecules that are the basis of living tissues — and they had to do so without the help of computer spreadsheets.

A painstakingly handwritten chart preserved by the U.S. National Library of Medicine shows how complicated the feat was.

It was filled in by biochemist Marshall W. Nirenberg and his colleagues at the National Institutes of Health. During the 1960s, they raced with other researchers to figure the universal code shared by every living organism’s cells.

Proteins consist of linked chains of amino acids, and they are made in two stages. First, the information in a molecule of DNA is transcribed into a messenger RNA (mRNA) molecule that consists of codons. Each codon consists of a three-unit combination of RNA nucleotides U, C, A and G. Cells then use the mRNA’s codons as instructions to create chains of amino acids that, taken together, equal proteins. The codons — 64 in all — also tell the cells when to start or stop amino acid chains.

In 1961, Nirenberg and his colleague, J. Heinrich Matthaei, proved that the combination UUU was decoded as the amino acid phenylalanine. Over the next five years, the team conducted more experiments to figure out which codons created which amino.

As they went along, their working chart — made of multiple pieces of tapedtogether paper — gained a vast collection of letter combinations, stars and circles. Nirenberg shared the 1968 Nobel Prize in physiology or medicine for his work on the code, a discovery that is known as one of the most significant in the history of science.