NIRENBERG, Marshall Warren

(b. 10 April 1927 in New York City), biochemist who won the 1968 Nobel Prize in physiology or medicine for his role in deciphering the genetic code. This key research, done in the 1960s, allowed biologists to begin to manipulate genes and thus opened the field of genetic engineering that blossomed at the end of the twentieth century.

Nirenberg's parents, Harry and Minerva (Bykowsky) Nirenberg, moved to Florida when he was ten years old. Nirenberg attended the University of Florida, receiving a B.S. in 1948 and a master's degree in biology four years later. He earned a doctorate in biochemistry at the University of Michigan in 1957. In the same year he began research at the National Institutes of Health (NIH) in Bethesda, Maryland. There he met Perola Zaltzman, a Brazilian biochemist, whom he married on 14 July 1961. In 1962 he was appointed head of the Section of Biochemical Genetics at NIH. Nirenberg has remained at NIH his entire career; he eventually became chief of the Laboratory of Biochemical Genetics in the National Heart, Lung, and Blood Institute.

In the late 1950s Nirenberg became one of the group of biochemists exploring the question of how the information in the molecule of heredity, deoxyribonucleic acid (DNA), is used by the body to make protein. Scientists were just realizing that another molecule, ribonucleic acid (RNA), was a go-between in this process, but the particulars were still unknown. DNA is a long, double-stranded molecule made up of four kinds of building blocks called nucleotides. The nucleotide sequence in DNA determines that in RNA, which is made up of four slightly different nucleotides. RNA, however, is often single-stranded, as Nirenberg demonstrated in his research.

In 1960 a German postdoctoral student, Heinrich Matthaei, joined Nirenberg, and together they studied RNA and how it is used in making protein. They devised a "cell-free" system by purifying bacteria of all the chemical components needed for protein synthesis, which is the process by which the information in the RNA nucleotide sequence is used to create the bonded string of amino acids that forms a protein. Protein synthesis involves using the information in one linear molecule, RNA, to make another linear molecule, protein. The simple system in a test tube that Nirenberg and Matthaei created was key to their further progress. They originally used RNA obtained from cells, but then they created a synthetic RNA molecule that was just a string of molecules of one nucleotide, uracil, rather than a molecule containing all four nucleotides. They found that using this synthetic RNA resulted in the creation of a protein containing only one of the twenty amino acids, namely phenylalanine. For theoretical reasons, biochemists had predicted that the genetic code would be a triplet code and that a string of three nucleotides would code for one amino acid. Subsequent work by Nirenberg and others verified this prediction. This meant that the RNA triplet of UUU (a string of three uracil nucleotides) was the code for phenylalanine.

Published in 1961, this momentous research showed it is possible to decipher the genetic code, and it put Nirenberg, a shy man, in the limelight. Over the next several years he and his colleagues synthesized a large number of other synthetic RNA molecules containing various combinations of nucleotides and thus painstakingly worked out much of the rest of the genetic code. Mathematically, positing four nucleotides in groups of three, taking into account the order within each triplet, there are sixty-four possible combinations, each a different nucleotide triplet code. Because there are only twenty amino acids, it is not surprising that most correspond with more than one triplet code. It turns out that two of the triplets do not code for any amino acid; instead, they are "stop" messages that signal the end of the sequence.

Nirenberg was joined in the deciphering effort by a number of researchers working in other laboratories. Most notable among these were the biochemist Har Gobind Khorana, who later shared the Nobel Prize with Nirenberg, and Severo Ochoa, who had already won the Nobel Prize for other research. By 1966 all sixty-four triplets had been deciphered. Nirenberg and Khorana were awarded the Nobel Prize a mere two years later, indicating the significance of the work. In fact, at the time, the work was considered the most important research performed in molecular biology since James Watson and Francis Crick had identified the structure of the DNA molecule in 1953. Robert W. Holley, who had discovered the role of another type of RNA in protein synthesis, shared the prize with Nirenberg and Khorana.

Like many of those who made important contributions to molecular biology, Nirenberg soon abandoned work on bacteria, figuring that the major discoveries in the field had been made. He then investigated what he considered the next great frontier in biological research: the development of the nervous system. In the late 1980s he studied fruit fly development, a major focus of research at the time. Drosophila homeobox genes are important in setting down the basic structure of the fly in early development; Nirenberg discovered four new ones. He moved on to studying molecular mechanisms that regulate gene expression during embryonic development, particularly with fruit flies and mice.

In the years after receiving the Nobel Prize, Nirenberg lent his support to a number of causes he saw as important to the future of science and of society. He advocated strong governmental support for research, and in 1992 he joined with an international group of 1,500 scientists in signing the "World Scientists' Warning to Humanity," which dealt with the dangers of the global environmental problems.

Nirenberg's careful dissection of the process of protein synthesis in the early 1960s and his first steps in breaking the genetic code were crucial to the development of the field of genetic engineering. His work was an essential contribution to the goal of manipulating genes, so in a very real sense the efforts of twenty-first–century scientists to engineer crops and genetic therapies for human disease are a direct outcome of his research.

Nirenberg's papers are held by the National Library of Medicine (NLM). Many are digitally available on the Marshall Nirenberg Papers Web site, part of the Profiles in Science Web site of NLM (2000), which can be found at <http://profiles.nlm.nih.gov/>. Biographical essays on Nirenberg appear in Current Biography (1965) and Modern Scientists and Engineers (1980). Carla Mecoli-Kamp's "Marshall Warren Nirenberg" is in Notable Twentieth-Century Scientists (1995).

Maura C. Flannery

Marshall Warren Nirenberg

Marshall Warren Nirenberg (born 1927) is best known for deciphering the portion of DNA (deoxyribonucleic acid) that is responsible for the synthesis of the numerous protein molecules which form the basis of living cells. In 1968 he was awarded the Nobel Prize for physiology or medicine.

Nirenberg's research has helped to unravel the DNA genetic code, aiding, for example, in the determination of which genes code for certain hereditary traits. For his contribution to the sciences of genetics and cell biochemistry, Nirenberg was awarded the 1968 Nobel Prize in physiology or medicine with Robert W. Holley and Har Gobind Khorana.

Nirenberg was born in New York City on April 10, 1927, and moved to Florida with his parents, Harry Edward and Minerva (Bykowsky) Nirenberg, when he was ten years old. He earned his B.S. in 1948 and his M.Sc. in biology in 1952 from the University of Florida. Nirenberg's interest in science extended beyond his formal studies. For two of his undergraduate years he worked as a teaching assistant in biology, and he also spent a brief period as a research assistant in the nutrition laboratory. In 1952, Nirenberg continued his graduate studies at the University of Michigan, this time in the field of biochemistry. Obtaining his Ph.D. in 1957, he wrote his dissertation on the uptake of hexose, a sugar molecule, by ascites tumor cells.

Shortly after earning his Ph.D., Nirenberg began his investigation into the inner workings of the genetic code as an American Cancer Society (ACS) fellow at the National Institutes of Health (NIH) in Bethesda, Maryland. Nirenberg continued his research at the NIH after the ACS fellowship ended in 1959, under another fellowship from the Public Health Service (PHS). In 1960, when the PHS fellowship ended, he joined the NIH staff permanently as a research scientist in biochemistry.

After only a brief time conducting research at the NIH, Nirenberg made his mark in genetic research with the most important scientific breakthrough since James D. Watson and Francis Crick discovered the structure of DNA in 1953. Specifically, he discovered the process for unraveling the code of DNA. This process allows scientists to determine the genetic basis of particular hereditary traits. In August of 1961, Nirenberg announced his discovery during a routine presentation of a research paper at a meeting of the International Congress of Biochemistry in Moscow.

Nirenberg's research involved the genetic code sequences for amino acids. Amino acids are the building blocks of protein. They link together to form the numerous protein molecules present in the human body. Nirenberg discovered how to determine which sequences patterns code for which amino acids (there are about 20 known amino acids).

Nirenberg's discovery has led to a better understanding of genetically determined diseases and, more controversially, to further research into the controlling of hereditary traits, or genetic engineering. For his research, Nirenberg was awarded the 1968 Nobel Prize for physiology or medicine. He shared the honor with scientists Har Gobind Khorana and Robert W. Holley. After receiving the Nobel Prize, Nirenberg switched his research focus to other areas of biochemistry, including cellular control mechanisms and the cell differentiation process.

Since first being hired by the NIH in 1960, Nirenberg has served in different capacities. From 1962 until 1966 he was Head of the Section for Biochemical Genetics, National Heart Institute. Since 1966 he has been serving as the Chief of the Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute. Other honors bestowed upon Nirenberg, in addition to the Nobel Prize, include honorary membership in the Harvey Society, the Molecular Biology Award from the National Academy of Sciences (1962), National Medal of Science presented by President Lyndon B. Johnson (1965), and the Louisa Gross Horwitz Prize for Biochemistry (1968). Nirenberg also received numerous honorary degrees from distinguished universities, including the University of Michigan (1965), University of Chicago (1965), Yale University (1965), University of Windsor (1966), George Washington University (1972), and the Weizmann Institute in Israel (1978). Nirenberg is a member of several professional societies, including the National Academy of Sciences, the Pontifical Academy of Sciences, the American Chemical Society, the Biophysical Society, and the Society for Developmental Biology.

Nirenberg married biochemist Perola Zaltzman in 1961. While described as being a reserved man who engages in little else besides scientific research, Nirenberg has been a strong advocate of government support for scientific research, believing this to be an important factor for the advancement of science.

Further Reading

Wasson, Tyler, editor, Nobel Prize Winners, H. W. Wilson, 1987, pp. 767-768.

New York Times, October 12, 1982, p. C3. □

NIRENBERG, MARSHALL WARREN

NIRENBERG, MARSHALL WARREN (1927– ), U.S. biochemist and Nobel Prize winner. Nirenberg was born in New York City and educated in Orlando, Florida. He received his B.Sc. (1948) and M.Sc. (1952) in zoology from the University of Florida at Gainesville and earned his Ph.D. in biochemistry from the University of Michigan at Ann Arbor, guided by Dr. James Hogg. He joined the staff of the National Institutes of Health, Bethesda, in 1957 where he was appointed chief of biochemical genetics at the National Heart Institute and where he has remained for the rest of his career. Nirenberg and his co-workers showed that genes control protein synthesis through dna sequences transmitted by rna. They elucidated the "language" dictating the synthesis of a single amino acid as the first step in understanding what is now termed the "genetic code." He was awarded the 1968 Nobel Prize for physiology or medicine jointly with Robert Holley and Har Gobind Khorana. Subsequently Nirenberg and his colleagues completed the task of unraveling the full code. He remained an active research worker investigating the conserved genes that control development called "homeoboxes" and the genes and factors that regulate the growth of cell lines derived from the nerve cell tumor, neuroblastoma. His many honors include election to the U.S. National Academy of Sciences (1967), the American Academy of Arts and Sciences, and the American Philosophical Society (2001). His awards include the U.S. National Medal of Science (1966), the Gairdner Award (1967), the Lasker Award in Basic Medical Science (1968), the U.S. National Medal of Honor (1968), and the Joseph Priestley Award (1968). Nirenberg showed great and often controversial interest in the social responsibilities of geneticists and was actively involved in action against world poverty and nuclear proliferation. He often protested against the political repression of fellow scientists including the Soviet refusal to allow Mikhail Stern to immigrate to Israel. He married the biochemist Perola Zaltzman in 1968.

[Michael Denman (2^nd ed.)]

Nirenberg, Marshall Warren (1927– ) US biochemist who found the key to the genetic code by deciphering different combinations of three nucleotide bases (called ‘codons’) within long nucleotide chains in DNA and RNA. He shared the 1968 Nobel Prize in physiology or medicine.