- Person
- Marshall Nirenberg
- Lived
- 1927–2010
- Field
- Biochemistry, genetics
- From
- American
The story
In 1961 Marshall Nirenberg and Heinrich Matthaei showed that a synthetic RNA made only of uracil directed the making of a protein made only of phenylalanine, revealing UUU as the first word of the genetic code. Further experiments soon showed that poly-C coded for proline and that poly-A coded for lysine. Then progress slowed. Long synthetic RNAs made from mixtures of two or more bases had their letters in random order, so they could show which letters made up a codon but not the order in which they came. With 64 possible three-letter combinations, Nirenberg's team needed a way to test each word individually.
In 1964 Philip Leder, a postdoctoral researcher in Nirenberg's laboratory, developed the answer, now known as the triplet binding assay. A tiny RNA of just three letters, a trinucleotide, was mixed with ribosomes. If its sequence matched, it would cause a particular transfer RNA, carrying its amino acid, to bind to the ribosome. Each transfer RNA was loaded with a radioactively labelled amino acid. The mixture was then poured through a nitrocellulose filter, which held back ribosomes but let free transfer RNA pass through. Any radioactivity caught on the filter revealed which amino acid that three-letter word specified. The National Library of Medicine describes the sophisticated filtration machine Leder built for the purpose.
The method gave quick, unambiguous answers. Leder found that GUU, UGU and UUG coded for valine, cysteine and leucine, showing that the order of letters mattered. Using the same approach, Merton Bernfield showed that UUU and UUC both coded for phenylalanine and that UCU and UCC both coded for serine, proving that the code is redundant, with several codons for one amino acid. The results appeared in 1964 in Science and in a series of papers in the Proceedings of the National Academy of Sciences.
The filter assay greatly sped up the work, and about 50 codons were assigned this way. Combined with the nucleic acid synthesis of Har Gobind Khorana, it allowed the code to be almost completely decoded by the 1966 Cold Spring Harbor Symposium, and that year Nirenberg announced he had deciphered the 64 codons for all twenty amino acids. Two years later he shared the Nobel Prize with Khorana and Robert Holley.
The dictionary their filter helped complete is the one every biologist, every genetic test and every genome analysis relies on today.
Why it matters
The method completed the genetic dictionary that every biologist and genetic test now relies on.
About Marshall Nirenberg
NIH biochemist who in 1961 read the first word of the genetic code, UUU for phenylalanine, then led the race to decipher all of it, sharing the 1968 Nobel Prize in Medicine.
More about Marshall Nirenberg
- Nirenberg's lab found genes that shape the nervous systemIn the late 1980s Marshall Nirenberg's laboratory discovered four new homeobox genes in fruit flies, NK-1 to NK-4, which help control nervous system development.
- Nirenberg uncovered a molecular basis of opiate withdrawalIn the early 1970s Marshall Nirenberg and Werner Klee showed how morphine suppresses a nerve-cell enzyme and how cells compensate, explaining tolerance and withdrawal.
- Nirenberg's nerve-cell lines served labs worldwideFrom the late 1960s Marshall Nirenberg built a bank of neuroblastoma cell lines with chosen nerve traits and supplied them to scientists worldwide for decades.
- NIH colleagues rallied to help Nirenberg crack the codeIn the 1961–62 'coding race' against Severo Ochoa's large lab, many NIH scientists set aside their own work to help Marshall Nirenberg decipher the genetic code.
- Marshall Nirenberg read the first word of the genetic codeAt 3 a.m. on 27 May 1961, Marshall Nirenberg's NIH experiment showed that the RNA 'word' UUU codes for phenylalanine, the first codon ever deciphered.
- Nirenberg warned society to prepare for genetic engineeringIn a 1967 Science editorial, Marshall Nirenberg predicted humans would one day program cells and urged society to prepare to use that power wisely.
- Nirenberg spoke up for persecuted scientists and peaceMarshall Nirenberg protested Brazil's 1969 purge of scientists, backed appeals against hunger and nuclear escalation, and urged ratification of the Chemical Weapons Convention.
Sources
- Translating the Code of Life and the Nobel Prize, 1962–1968 NLM Profiles in Science
- Marshall Warren Nirenberg Wikipedia
- The Marshall W. Nirenberg Papers: Biographical Overview NLM Profiles in Science
- Nirenberg and Leder experiment Wikipedia
Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.