Scientist who wrote the language of life

To each of these molecules is attached one of four chemical bases, called nucleotides — adenine, cytosine, guanine and thymine. However, no one knew how combinations of these bases made the 20 or so amino acids from which proteins are built, or how the information they held was transcribed.

This was the genetic code, and in 1961 it was deciphered by Marshall Nirenberg. It was, as a colleague put it, “the common language used throughout living matter, from the simplest virus to the most complicated human beings”. A young and unknown researcher at the time, Nirenberg shared the 1968 Nobel prize in physiology or medicine with Har Gobind Khorana and Robert Holley for this work. A modest man who felt discovery was its own reward, Nirenberg deserved to be as famous as the flamboyant Watson and Crick. “It was this work and the sequel,” said the geneticist Sir Walter Bodmer, “that eventually, together with that of Khorana, with whom Nirenberg shared the Nobel prize, laid the foundation for being able to decipher the ‘language of life’. The outcome was quite fundamental to all subsequent work in molecular biology, and so to almost all the developments that are taking place in our fundamental understanding of biological processes.”

Significant change
Nirenberg made the discovery shortly after he had been given a permanent contract at the US government-funded National Institutes of Health (NIH). He had joined NIH three years earlier, in 1957, as a postdoctoral fellow to work on glucose transport and glycogen metabolism, but changed to protein synthesis, considering it to be one of the most exciting areas in biochemistry. He was joined by a young German postdoctoral plant physiologist, Johann Heinrich Matthaei.

By then, Crick and the biologist Sydney Brenner had shown, mainly on theoretical grounds, that the code must be in triplets called ‘codons’, composed of various combinations of the four bases. With Matthaei, Nirenberg homogenised cells to break them down, giving a cell-free system to which they added uracil, a nucleotide absent from DNA but present in RNA. Thus, if an amino acid were made, it could only have come from nucleotides in the RNA. The protein that emerged was phenylalanine. It was therefore clear that the code for phenylalanine was three uracil molecules, known as UUU. This was the first word to be discovered in the chemical dictionary of life.
They were lucky their experiment worked: no one then knew that the natural messenger RNA carried at its front end a codon that says ‘start here’. Fortunately, Nirenberg and Matthaei’s soup of mashed-up cells contained double the usual amount of magnesium, which overrode the need for a start codon.

Shortly afterwards, Nirenberg presented his findings to a sparsely filled room at a molecular biology conference in Moscow. One of the audience recognised the importance of what he had heard and told Crick, who arranged for Nirenberg to repeat the talk next day in a lecture theatre packed with a thousand people.
Nirenberg and Matthaei, working day and night, went on to unravel the other 63 codes for the remaining amino acids, completing this in 1965. They succeeded thanks to colleagues, who dropped their own research to help, and despite intense competition from other, better-known and better-funded, scientists. When Nirenberg and Matthaei started this work, they were new boys and outsiders — so much so that they had not heard of messenger RNA. Later, Nirenberg went on to make discoveries in neuroscience, neural development and the homeobox genes.
The Guardian