Marshall Warren Nirenberg – Genetics Scientist. How he Cracked the Genetic Code

Personal Life, Education and Career

Born on 10 April 1927 in New York to Harry and Minerva Nirenberg, Marshall Nirenberg and his family moved to Orlando, Florida, and he grew up there, interested in biology and with a habit of keeping neat records of his flora and fauna observations.

After graduating from high school in 1945, he got a B.Sc. degree in zoology and chemistry in 1948 and a M.Sc. degree in zoology in 1952 from the University of Florida. He got his Ph.D. in biological chemistry from the University of Michigan at Ann Arbor in 1957 and then, in 1957-1959, did postdoctoral work as an American Cancer Society Postdoctoral Fellow at the National Institute of Arthritis, Metabolic, and Digestive Diseases (NIAMDD), National Institutes of Health (NIH), in Bethesda, Maryland. He was a Public Health Service Postdoctoral Fellow at NIAMDD in 1959-1960.

He became a research biochemist at NIAMDD in 1960. Between 1962-1966, he served as the Chief of the Section on Biochemical Genetics at the National Heart Institute (NHI), NIH. He became the Senior Research Biochemist and Chief at the Laboratory of Biochemical Genetics, NHI.

He received numerous honors and awards from leading scientific organizations, like the Molecular Biology Award from the National Academy of Sciences in 1962 in the course of his career, as well as the National Medal of Science (1966) and the National Medal of Honor (1968) from President Lyndon Johnson. In 2001, he became a member of the American Philosophical Society.

DNA Replication and Gene Expression

In the late 1950s, Marshall Nirenberg became interested in finding out what part, if any, RNA played in bringing about DNA replication and gene expression.

Despite having no formal training in molecular biology, he set out on the quest to discover if, as some researchers were beginning to think, RNA conveyed information from DNA to the proteins and, if so, how exactly this took place.

Working first with the German postdoctoral student J. Heinrich Matthaei and then eventually with a team of researchers, Nirenberg succeeded in proving that messenger RNA (mRNA) did indeed transcribe genetic information from the DNA and then direct protein synthesis.

Protein Synthesis

At the start, the researchers studied the base molecular units of DNA and RNA – the four nucleotides, adenosine, cytosine, guanine and thymine. Using E-coli bacteria for the research, they made and inserted synthetic RNA into the bacterial cell and observed that three unit batches of Uracil (UUU or poly-U) in the RNA directed the formation of the amino acid phenylalanine and the composition of an amino acid chain that formed proteins.

The three unit Uracil batches, the researchers realized, obtained genetic information from the DNA and directed the formation of proteins. This meant the Uracil batches were what they were looking for – the messenger RNA.

This research was published in a paper ‘The Dependence of Cell-Free Protein Synthesis in E.Coli upon Naturally Occurring or Synthetic Polyribonucleotides’ in the Proceedings of the National Academy of Sciences and presented in a lecture at the International Congress of Biochemistry held in Moscow that same month. The Poly-U experiments caused quite a stir in the scientific community and brought the researchers plenty of publicity.

Cracking the Genetic Code

Having cracked the genetic code, Nirenberg and his research team devoted the next five years to discovering the codes for the other amino acids. They found codons for lysine (AAA or three adenosines) and proline (CCC or three cytosines). GGG or three guanines, they found, did not function as a messenger. They also discovered that replacing one or two units of a three-batch unit with any other nucleotides could create other amino acids; there were 64 possible codon combinations and the researchers were able to find out the nucleotide order in the codons and decipher all 64 by 1966.

This noteworthy achievement led to the Nobel Prize in Physiology or Medicine in 1968; he shared it with Robert W. Holley and Har Gobind Khorana. Nirenberg then turned his attention to neurobiology and spent the next thirty years doing research on the neuroblastoma system (1967), the effects of morphine on the nervous system (1973), neural cell receptors (1976) and Homeobox genes in Drosophila (1989).