Marshall Warren Nirenberg was born on April 10, 1927, in New York City, He developed an early interest in biology. In 1948, he received his B.S. degree and, in 1952, a master's degree in zoology from the University of Florida at Gainesville. He received his Ph.D. in biochemistry from the University of Michigan, Ann Arbor in 1957.
He began his postdoctoral work at the National Institutes of Health (NIH) in 1957 as a fellow of the American Cancer Society. In 1960, he became a research biochemist at the NIH. In 1959, he began to study the steps that relate DNA, RNA and protein. Nirenberg's groundbreaking experiments advanced him to become the head of the Section of Biochemical Genetics in 1962.
Nirenberg was awarded the National Medal of Science in 1966 and the National Medal of Honor in 1968 by President Lyndon B. Johnson. In 1968, he won the Nobel Prize in Medicine with Har Khorana and Robert Holley, for describing the genetic code and how it operates in protein synthesis. He was elected to the American Philosophical Society in 2001.
By 1959, experiments by Oswald Avery, Francis Crick, James D. Watson, and others had shown DNA to be the molecule of genetic information. It was not known, however, how DNA was replicated, how DNA directed the expression of proteins, or what role RNA had in these processes. Nirenberg teamed up with Heinrich J. Matthaei at the National Institutes of Health to answer these questions. They produced RNA comprised solely of uracil, a nucleotide that only occurs in RNA. They then added this synthetic poly-uracil RNA into a cell-free extract of Escherichia coli which contained the DNA, RNA, ribosomes and other cellular machinery for protein synthesis. They added DNase, which breaks apart the DNA, so that no additional proteins would be produced other than that from their synthetic RNA. They then added 1 radioactively labeled amino acid, the building blocks of proteins, and 19 unlabeled amino acids to the extract, varying the labeled amino acid in each sample. In the extract containing the radioactively labeled phenylalanine, the resulting protein was also radioactive. They realized that they had found the genetic code for phenylalanine: UUU (three uracil bases in a row) on RNA. This was the first step in deciphering the codons of the genetic code and the first demonstration of messenger RNA.
Within a few years, his research team had performed similar experiments and found that three-base repeats of adenosine (AAA) produced the amino acid lysine, cytosine repeats (CCC) produced proline and guanine repeats (GGG) produced nothing at all. The next breakthrough came when Phillip Leder, a postdoctoral researcher in Nirenberg's lab, developed a method for determining the genetic code on pieces of tRNA. This greatly sped up the assignment of three-base codons to amino acids so that 50 codons were identified in this way. Khorana's experiments confirmed these results and completed the genetic code translation.
Nirenberg's later research focused on neuroscience, neural development, and the homeobox genes.