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Figure 10.10 Deciphering the Genetic Code In 1961, Nirenberg and Matthaei cracked the genetic code by using an artificial mRNA in which all of the bases were uracil (poly U). In this experiment, the scientists prepared a bacterial extract that contained all of the components needed to translate proteins and then added the mRNA homopolymer. Results showed that the cell-free extract produced a polypeptide composed entirely of the amino acid phenylalanine. Similarly, Nirenberg and Matthaei went on to test poly A and poly C, which produced lysine and proline, respectively. Although at the time the pair did not test poly G due to technical difficulties with mRNA synthesis, this homopolymer would have resulted in the production of glycine. This experiment, commonly referred to as “the poly U experiment,” laid the foundation for Nirenberg’s groundbreaking work on the genetic code. He continued working on the code until he had completely deciphered it in 1966. Two years later, Nirenberg shared the Nobel Prize in Physiology or Medicine 1968 with two other scientists “for their interpretation of the genetic code and its function in protein synthesis.” Original Papers Nirenberg, M. W., and J. H. Matthaei. 1961. The dependence of cell-free protein synthesis in E. coli upon naturally occurring or synthetic polyribonucleotides. Proceedings of the National Academy of Sciences 47: 1588–1602. http://www.pnas.org/content/47/10/1588.full.pdf+html Nirenberg, M. W., J. H. Matthaei, and O. W. Jones Jr. 1962. An intermediate in the biosynthesis of polyphenylalanine directed by synthetic template RNA. Proceedings of the National Academy of Sciences 48: 104–109. http://www.pnas.org/content/48/1/104.full.pdf+html Matthaei, J. H., O. W. Jones Jr., R. G. Martin, and M. W. Nirenberg. 1962. Characteristics and composition of RNA coding units. Proceedings of the National Academy of Sciences 48: 666– 677. http://www.pnas.org/content/48/4/666.full.pdf+html Jones, O.W. Jr., and M. W. Nirenberg. 1962. Qualitative survey of RNA codewords. Proceedings of the National Academy of Sciences 48: 2115–2123. http://www.pnas.org/content/48/12/2115.full.pdf+html Nirenberg, M. W., J. H. Matthaei, O. W. Jones Jr., R. G. Martin, and S. H. Barondes. 1963. Approximation of Genetic Code Via Cell-Free Protein Synthesis Directed by Template RNA. Federation Proceedings 22: 55–61. http://profiles.nlm.nih.gov/JJ/B/B/J/J/ Nirenberg, M. W., P. Leder, M. Bernfield, R. Brimacombe, J. Trupin, F. Rottman, and C. O'Neal. 1965. RNA codewords and protein synthesis, VII. On the general nature of the RNA code. Proceedings of the National Academy of Sciences 53: 1161–1168. http://www.pnas.org/content/53/5/1161.full.pdf+html Links Smith, A. 2008. Nucleic Acids to Amino Acids: DNA Specifies Protein. Nature Education 1(1) http://www.nature.com/scitable/topicpage/Nucleic-Acids-to-Amino-Acids-DNA-Specifies-935 Ralston, A., and K. Shaw. 2008. Reading the Genetic Code. Nature Education 1(1) http://www.nature.com/scitable/topicpage/Reading-the-Genetic-Code-1042 Dr. Marshall Nirenberg: The Nobel Prize in Physiology or Medicine 1968 http://nobelprize.org/nobel_prizes/medicine/laureates/1968/ Nobel prize.org: Crack the Code http://nobelprize.org/educational_games/medicine/gene-code/index.html Lasker Foundation: An Interview with Marshall Nirenberg http://www.laskerfoundation.org/media/v_nirenberg.htm Genome News Network: Marshall Nirenberg (1927–2010) Cracks the Genetic Code http://www.genomenewsnetwork.org/resources/timeline/1961_Nirenberg.php Office of NIH History: The Poly-U Experiment http://history.nih.gov/exhibits/nirenberg/HS4_polyU.htm National Library of Medicine: Profiles in Science: The Marshall W. Nirenberg Papers: Synthetic RNA and the Poly-U Experiments, 1957–1962 http://profiles.nlm.nih.gov/JJ/Views/Exhibit/narrative/syntheticrna.html National Library of Medicine: Profiles in Science: The Marshall W. Nirenberg Papers: Translating the Code of Life and the Nobel Prize, 1962–1968 http://profiles.nlm.nih.gov/JJ/Views/Exhibit/narrative/codeoflife.html Wall Street Journal: Scientist Set Stage for Genetic Engineering http://online.wsj.com/article/SB10001424052748703626604575011450122739496.html