Marshall Warren Nirenberg
|Marshall Warren Nirenberg|
Nirenberg in 2003
|Born||April 10, 1927
New York City
|Died||January 15, 2010
New York City
|Known for||genetic code|
|Notable awards||NAS Award in Molecular Biology (1962)
Gairdner Foundation International Award (1967)
Nobel Prize in Physiology or Medicine (1968)
Franklin Medal (1968)
|Spouse||Perola Zaltzman-Nirenberg (1961-2001; her death)
Myrna M. Weissman (m. 2005)
Marshall Warren Nirenberg (April 10, 1927 – January 15, 2010) was an American biochemist and geneticist. He shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" and describing how it operates in protein synthesis. In the same year, together with Har Gobind Khorana, he was awarded the Louisa Gross Horwitz Prize from Columbia University.
By 1959, experiments and analysis such as the Avery-MacLeod-McCarty experiment, the Hershey-Chase experiment, the Watson-Crick structure and the Meselson-Stahl experiment had shown DNA to be the molecule of genetic information. It was not known, however, 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 composed 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 (see Nirenberg and Matthaei experiment).
In August 1961, at the International Congress of Biochemistry in Moscow, Nirenberg presented a paper to a small group of scientists. Francis Crick convinced the conference leaders to invite Nirenberg to repeat his performance the next day. Speaking before the assembled congress of more than a thousand people, Nirenberg electrified the scientific community. He quickly received great scientific attention for these experiments. 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, and cytosine repeats (CCC) produced proline. The next breakthrough came when Philip Leder, a postdoctoral researcher in Nirenberg's lab, developed a method for determining the genetic code on pieces of tRNA (see Nirenberg and Leder experiment). 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.
The period between 1961 and 1962 is often referred to as the "coding race" because of the competition between the labs of Nirenberg at NIH and Nobel laureate Severo Ochoa at New York University Medical School, who had a massive staff. Faced with the possibility of helping the first NIH scientist win a Nobel prize, many NIH scientists put aside their own work to help Nirenberg in deciphering the mRNA codons for amino acids. Dr. DeWitt Stetten, Jr., director of the National Institute of Arthritis and Metabolic Diseases, called this period of collaboration "NIH's finest hour".
Nirenberg was born in New York City, the son of Minerva (Bykowsky) and Harry Edward Nirenberg, a shirtmaker. He developed rheumatic fever as a boy, so the family moved to Orlando, Florida to take advantage of the subtropical climate. 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 where he was also a member of the Pi Lambda Phi Fraternity. His dissertation for the Master's thesis was an ecological and taxonomic study of caddis flies (Trichoptera). 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 what was then called the National Institute of Arthritis and Metabolic Diseases. In 1959 he became a research biochemist at the NIH and 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 in the National Heart Institute (now the National Heart, Lung, and Blood Institute), where he remained a laboratory chief until his death. Fellow laboratory chiefs included Ernst Freese and Daniel Carleton Gajdusek. He was married in 1961 to Perola Zaltzman, a chemist from the University of Brazil, Rio de Janeiro, who also worked at NIH and died in 2001. Nirenberg married Myrna M. Weissman, Ph.D., Professor of Epidemiology and Psychiatry at Columbia University College of Physicians and Surgeons in 2005. He had four stepchildren: Susan Weissman of Evanston, Illinois, Judith Weissman of New York, New York, Sharon Weissman of New Haven, Connecticut, and Jonathan Weissman of San Francisco, California. He is also survived by his sister, Joan Nirenberg Geiger of Dallas, TX, several nieces and a nephew.
Nirenberg was awarded the National Medal of Science in 1964 and the National Medal of Honor in 1968 by President Lyndon B. Johnson. He was elected to the American Philosophical Society in 2001. He died on January 15, 2010, from cancer after several months of illness.
- Wade, Nicholas (January 21, 2010), "Marshall Nirenberg, Biologist Who Untangled Genetic Code, Dies at 82", NY Times.
- Leder, P; Nirenberg, MW (1964), "RNA CODEWORDS AND PROTEIN SYNTHESIS, III. ON THE NUCLEOTIDE SEQUENCE OF A CYSTEINE AND A LEUCINE RNA CODEWORD", Proceedings of the National Academy of Sciences (December 1964) 52 (6): 1521–1529, Bibcode:1964PNAS...52.1521L, doi:10.1073/pnas.52.6.1521, PMC 300480, PMID 14243527
- Eiserling, F; Levin, JG; Byrne, R; Karlsson, U; Nirenberg, MW; Sjoestrand, FS (1964), "Polyribosomes and DNA-dependent Amino Acid Incorporation in Escherichia coli Extracts", Journal of Molecular Biology (December 1964) 10 (3): 536–40, doi:10.1016/S0022-2836(64)80073-5, PMID 14257696
- BLADEN, HA; BYRNE, R; LEVIN, JG; NIRENBERG, MW (1965), "AN ELECTRON MICROSCOPIC STUDY OF A DNA-RIBOSOME COMPLEX FORMED IN VITRO", J. Mol. Biol. (Jan 1965) 11: 78–83, doi:10.1016/S0022-2836(65)80172-3, PMID 14255762
- BERNFIELD, MR; NIRENBERG, MW (1965), "RNA CODEWORDS AND PROTEIN SYNTHESIS. THE NUCLEOTIDE SEQUENCES OF MULTIPLE CODEWORDS FOR PHENYLALANINE, SERINE, LEUCINE, AND PROLINE", Science (Jan 29, 1965) 147 (3657): 479–84, Bibcode:1965Sci...147..479B, doi:10.1126/science.147.3657.479, PMID 14237203
- TRUPIN, JS; ROTTMAN, FM; BRIMACOMBE, RL; LEDER, P; Bernfield, MR; Nirenberg, MW (1965), "RNA CODEWORDS AND PROTEIN SYNTHESIS, VI. ON THE NUCLEOTIDE SEQUENCES OF DEGENERATE CODEWORD SETS FOR ISOLEUCINE, TYROSINE, ASPARAGINE, AND LYSINE", Proc. Natl. Acad. Sci. U.S.A. (Apr 1965) 53 (4): 807–11, Bibcode:1965PNAS...53..807T, doi:10.1073/pnas.53.4.807, PMC 221071, PMID 14324538
- Jones, OW; Nirenberg, MW (1966), "Degeneracy in the amino acid code", Biochim. Biophys. Acta (May 19, 1966) 119 (2): 400–6, doi:10.1016/0005-2787(66)90198-5, PMID 5335948
- Kellogg, DA; Doctor, BP; Loebel, JE; Nirenberg, MW (1966), "RNA codons and protein synthesis. IX. Synonym codon recognition by multiple species of valine-, alanine-, and methionine-sRNA", Proc. Natl. Acad. Sci. U.S.A. (Apr 1966) 55 (4): 912–9, Bibcode:1966PNAS...55..912K, doi:10.1073/pnas.55.4.912, PMC 224250, PMID 5327071
- Caskey, C. Thomas (Mar 2010), "Obituary: Marshall Nirenberg (1927–2010)", Nature 464 (7285): 44, Bibcode:2010Natur.464...44C, doi:10.1038/464044a, PMID 20203601
- Leder, Philip (Feb 2010), "Retrospective. Marshall Warren Nirenberg (1927–2010)", Science 327 (5968): 972, doi:10.1126/science.1187484, PMID 20167780
- The PolyU Experiment. history.nih.gov
- Membership Directory, 2010, Pi Lambda Phi Inc.
- Voet, Donald and Judith G. Voet. 1995. Biochemistry 2nd ed. John Wilely & Sons, New York.
- U.S. National Library of Medicine. "Profiles in Science: The Marshall W. Nirenberg Papers".
- Nobel Biography
- Marshall Nirenberg Papers (1937–2003) – National Library of Medicine finding aid
- The Marshall Nirenberg Papers – Profiles in Science, National Library of Medicine
- Free to View Video Interview with Marshall W. Nirenberg provided by the Vega Science Trust.
- The Life and Scientific Work of Marshall W. Nirenberg. (From Richard Olson & Roger Smith (eds.) The Biographical Encyclopedia of Scientists. 1998.)
- The Official Site of Louisa Gross Horwitz Prize
- Ed Regis (November 2007), "The Forgotten Code Cracker", Scientific American (print ) (Scientific American, Inc.) 297 (5): 50–51, Bibcode:2007SciAm.297e..50R, doi:10.1038/scientificamerican1107-50, PMID 17990823, "(subtitle) In the 1960s Marshall W. Nirenberg deciphered the genetic code, the combination of A, T, G and C nucleotides that specify amino acids. So why do people think that Francis Crick did it?"