Marshall NirenbergMarshall NirenbergThe Life and Scientific Work of
Marshall W. Nirenberg

by
Nigel J.T. Thomas Ph.D.
California State University, Los Angeles.
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[Published in: Richard Olson & Roger Smith (eds.) The Biographical Encyclopedia of Scientists. New York: Marshall Cavendish ©, 1998.
(The encyclopedia is aimed at Junior High and High School students. Length and format requirements were quite strict.)]



Areas of Achievement: Biochemistry, genetics, cell biology.

Contribution: Nirenberg was the scientist most responsible for deciphering the genetic code.


Early Life

Marshall Nirenberg was born in New York city, but, when he was ten years old, his family moved to Orlando, Florida. Marshall soon came to consider himself a Floridian.

In 1944 he enrolled at the University of Florida, studying zoology and botany, subjects that had long interested him. Whilst still an undergraduate he worked as a laboratory assistant and even as a teaching assistant; and while working in the Nutrition Laboratory he was introduced to biochemistry, then little studied at the undergraduate level. He learned how to use radioactive isotopes to follow the course of biochemical reactions, a technique that was to prove vital to his later research.

He graduated in 1948, but stayed on for graduate studies in biology, continuing to work in the Nutrition Laboratory. His master's thesis dealt with the classification and ecology of caddis flies, but in 1952 he began doctoral study in biochemistry at the University of Michigan. His doctoral thesis concerned the uptake of sugars by cancer cells, and he afterwards received a fellowship from the American Cancer Society for research at the National Institutes of Health, in Bethesda, Maryland. In 1960 he was appointed to the regular staff there.

Cracking the Code

Shortly after this appointment, Nirenberg began to collaborate with German scientist Johann Matthaei. They prepared an extract from bacterial cells that could make protein even when no intact living cells were present. Adding an artificial form of RNA, polyuridylic acid, to this extract caused it to make an unnatural protein composed entirely of the amino acid phenylalanine. This provided the first clue to the 'code' through which RNA (and, ultimately, DNA) control the production of specific types of protein in the living cell.

Nirenberg announced these results at the International Congress of Biochemistry, in Moscow, August 1961. As an unknown scientist with an obscurely titled paper, his initial talk was very poorly attended. However, he was asked to repeat it for the final session of the full Congress. Some listeners recall being 'electrified' by what they heard (although others, apparently, slept through it).

Over the next few years many similar experiments were done, by Nirenberg and others, using different forms of synthetic RNA to stimulate protein production. However, only modest further progress could be made in deciphering the code by such methods. But in 1964 Nirenberg announced that he and Philip Leder had devised a new and more powerful decoding technique, and within a year the code was fully deciphered.

After the Code

A shy, unassuming man, Nirenberg has a reputation for total dedication to his science. In 1966 he was appointed Chief of Biochemical Genetics at the National Heart, Lung, and Blood Institute, a post he still (in 1997) holds. In 1968 he received the Nobel Prize. He has continued to work on the very complex problems of understanding how genetic information controls the development and metabolism of living organisms.

Bibliography

By Nirenberg

About Nirenberg


SCIENCE SECTION:
The Genetic Code

The structures and properties of proteins are controlled by the sequence of bases in DNA and RNA.

Proteins are very large complex molecules that direct the vast array of chemical reactions that occur within living organisms and which constitute the life of those organisms. Many structural components of organisms are also proteins. The DNA in any living thing determines what sorts of proteins its cells can make, and thus what sort of organism it is: ant or oak tree, man or woman, blonde or brunette, and so on.

All protein molecules consist of very long chains of simple components called amino acids. There are just twenty types of amino acid in proteins, but the different orders in which they can be arranged in the chain give rise to many sorts of proteins, with very different biochemical properties. DNA contains the instructions, in coded form, for assembling amino acids into proteins in the right order, but DNA does not control protein production directly. When needed, its code is copied into a related substance called RNA. This comes in three forms: rRNA, which forms ribosomes, the intracellular bodies where proteins are actually assembled; tRNA, which carries the amino acids to the ribosomes; and messenger or mRNA, which carries the actual instructions for protein assembly.

RNA (like DNA) is itself a long chain molecule, and it is the order of the components called bases in the mRNA chain that codes for the order of amino acids in the protein. The bases may be considered as the letters in which the code is written, but there are only four types of base (designated as A, G, C, and U), so it takes a 'word' (or codon) consisting of three bases, in order, to specify a particular amino acid.


Figure1.

Protein Synthesis

Protein synthesis is directed by messenger RNA. The order of the amino acids in the protein chain is controlled by the order of the bases in the mRNA chain. It takes a codon of three bases to specify one amino acid.
Protein synthesis from mRNA


This much was suspected (if not yet proven) when Nirenberg began his work, but it was not known which codons specified which particular amino acids. However, when Nirenberg and Matthaei added an artificial mRNA containing only the base uracil (U) to their bacterial extract (containing ribosomes, tRNA, free amino acids, and other necessary components), they found that an unnatural protein chain was produced containing only the amino acid phenylalanine. Thus UUU is the code 'word' for phenylalanine.

Further experiments followed with other artificial mRNAs, but it was not then known how to make long artificial RNA chains with different bases in a particular order, so it was impossible to solve much of the code this way. However, Nirenberg and Leder found that RNA chains just three base units long (single codons, in effect), which could be made with bases in a specific order, would cause tRNA carrying the appropriate amino acid to stick fast to the ribosomes. These ribosomes were then filtered out, and the particular amino acid stuck to them could be determined by standard radioactive isotope techniques. The entire code was quickly deciphered.


Figure 2.

The Genetic Code.

The amino acid specified by any codon can be found by looking for the wide row designated by the first base letter of the codon shown on the left, then the column designated by the second base letter along the top, and finally the narrow row marked on the right, in the appropriate wide row, by the third letter of the codon. Many amino acids are represented by more than one codon. The codons UAA, UAG, and UGA do not specify an amino acid, but are instead used to signal where a protein chain should end.

+--------------------------------------------------------------------------+
¦ 2nd-> ¦       U       ¦      C      ¦       A       ¦       G      ¦     ¦
¦       ¦               ¦             ¦               ¦              ¦     ¦
¦  1st  ¦               ¦             ¦               ¦              ¦ 3rd ¦
¦   |   ¦               ¦             ¦               ¦              ¦  |  ¦
¦   V   ¦               ¦             ¦               ¦              ¦  V  ¦
¦-------+---------------+-------------+---------------+--------------+-----¦
¦   U   ¦ Phenylalanine ¦   Serine    ¦   Tyrosine    ¦   Cysteine   ¦  U  ¦
¦       ¦ Phenylalanine ¦   Serine    ¦   Tyrosine    ¦   Cysteine   ¦  C  ¦
¦       ¦    Leucine    ¦   Serine    ¦   END CHAIN   ¦   END CHAIN  ¦  A  ¦
¦       ¦    Leucine    ¦   Serine    ¦   END CHAIN   ¦  Tryptophan  ¦  G  ¦
¦-------+---------------+-------------+---------------+--------------+-----¦
¦   C   ¦    Leucine    ¦   Proline   ¦   Histidine   ¦   Arginine   ¦  U  ¦
¦       ¦    Leucine    ¦   Proline   ¦   Histidine   ¦   Arginine   ¦  C  ¦
¦       ¦    Leucine    ¦   Proline   ¦   Glutamine   ¦   Arginine   ¦  A  ¦
¦       ¦    Leucine    ¦   Proline   ¦   Glutamine   ¦   Arginine   ¦  G  ¦
¦-------+---------------+-------------+---------------+--------------+-----¦
¦   A   ¦  Isoleucine   ¦  Threonine  ¦  Asparagine   ¦    Serine    ¦  U  ¦
¦       ¦  Isoleucine   ¦  Threonine  ¦  Asparagine   ¦    Serine    ¦  C  ¦
¦       ¦  Isoleucine   ¦  Threonine  ¦    Lysine     ¦   Arginine   ¦  A  ¦
¦       ¦  Methionine   ¦  Threonine  ¦    Lysine     ¦   Arginine   ¦  G  ¦
¦-------+---------------+-------------+---------------+--------------+-----¦
¦   G   ¦    Valine     ¦   Alanine   ¦ Aspartic acid ¦    Glycine   ¦  U  ¦
¦       ¦    Valine     ¦   Alanine   ¦ Aspartic acid ¦    Glycine   ¦  C  ¦
¦       ¦    Valine     ¦   Alanine   ¦ Glutamic acid ¦    Glycine   ¦  A  ¦
¦       ¦    Valine     ¦   Alanine   ¦ Glutamic acid ¦    Glycine   ¦  G  ¦
+--------------------------------------------------------------------------+


Bibliography


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Much further information about Marshall Nirenberg, including an online archive of his papers, is now available at the National Library of Medicine Profiles in Science website (see also this press release and this obituary). This material was not available to me when I wrote the above article. - N.J.T.T.


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