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Marshall Nirenberg read the first word of the genetic code

At 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.

Marshall Nirenberg
Marshall Nirenberg · 1927–2010
Person
Marshall Nirenberg
Lived
1927–2010
Field
Biochemistry, genetics
From
American

The story

By the late 1950s scientists knew that DNA carries hereditary information, and in 1953 Watson and Crick had described its double helix. But nobody knew the dictionary that turns DNA's four-letter chemical alphabet into the twenty amino acids that make up proteins, or exactly how RNA carried the message. Theorists had argued that the code must use three-letter words, giving 64 possible combinations.

Marshall Nirenberg was an unlikely person to find it. Born in New York in 1927 to a Jewish family, he was a biochemist at the National Institutes of Health with no formal training in molecular genetics; he had only attended evening genetics classes at NIH, and some colleagues thought his plan was professional suicide. In 1960 he was joined by J. Heinrich Matthaei, a young postdoctoral researcher from the University of Bonn.

Following work by Alfred Tissières, they built a cell-free system from broken-open E. coli bacteria, which could make protein only when the right kind of RNA was added. They fed it a synthetic RNA made of a single repeated letter, uracil, called poly-U, supplied by their NIH colleagues Leon Heppel and Maxine Singer. In each test tube all twenty amino acids were present, but only one was radioactively labelled, and they changed the labelled one each time.

At 3 a.m. on 27 May 1961, Matthaei tried phenylalanine. After an hour, the control tube without poly-U showed about 70 counts; the tube with poly-U showed 38,000 counts per milligram of protein. A string of Us had made a chain of phenylalanine. Further tests confirmed that the product was polyphenylalanine.

The first word of the genetic code, UUU, had been read. It was also the first demonstration of messenger RNA at work, proof that RNA carries the instructions that tell cells which proteins to make. Nirenberg and Matthaei published the result in the Proceedings of the National Academy of Sciences in August 1961, and Nirenberg's talk in Moscow that month made them famous.

Within five years Nirenberg's team had deciphered all 64 codons, work that earned him a share of the 1968 Nobel Prize. Every genetic test, genome sequence and mRNA vaccine today depends on the dictionary that began with that one test tube.

Why it matters

Nirenberg's experiment opened the way to reading the entire genetic code, the foundation of modern genetics and medicine.

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.

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Marshall Nirenberg
1927–2010 · Biochemistry, genetics
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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.

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