|
|
|
Marshall W. Nirenberg
Biochemistry Alumnus Solves the Genetic Code
by Lee Katterman
Office of the Vice President for Research
"The last few decades of research have yielded an explosion of biological information," as noted by the University of Michigan Life Science Commission in its February, 1999 report. One of the early discoveries that ignited research in the life sciences was made by Marshall Nirenberg, a graduate of the UM Department of Biological Chemistry in the Medical School. In 1968, Nirenberg shared the Nobel Prize in Medicine for his work to "crack" the genetic code by determining how the information found in DNA molecules was used to guide the synthesis of cellular proteins.
Nirenberg was born in New York City on April 10th, 1927, the son of Harry and Minerva Nirenberg. In 1939, when Marshall was ten, his family moved to Orlando, Florida. (Of course, back then, central Florida was primarily an agricultural area with lots of open space.) It was here that Nirenberg first developed his interest in biology.
When it came time for college, Nirenberg enrolled in the University of Florida in Gainesville, where he studied zoology and botany. While an undergraduate, he got involved in research as a laboratory assistant in the Nutrition Laboratory at the University of Florida. Through this work, Nirenberg was introduced to biochemistry, at the time little studied at the undergraduate level. His involvement in research gave him the chance to learn about the use of radioactive isotopes to follow the course of biochemical reactions -- basic knowledge that Nirenberg would put to good use later in the research that led to the Nobel Prize.
In 1948, Nirenberg received a Bachelor's degree and then began working on his Master's degree. His thesis work focused on the ecology and classification of the caddis fly, a freshwater insect.
His growing interest in biochemistry led Nirenberg to continue his education at Michigan, where he enrolled in the biological chemistry Ph.D. program. As it turns out, the grades Nirenberg brought with him were not spectacular, and he was accepted on probationary status.
But as Nirenberg became more deeply involved in research in the lab of Professor James Hogg, things improved for him. He was very excited about his research project -- a study of an enzyme system that facilitated sugar uptake by tumor cells -- and spent many hours in the lab. Ultimately, he completed a fine thesis, and he graduated in 1957.
"The University should be quite proud for attracting a student as gifted as Nirenberg and for providing the research environment in which he could flourish," says Minor Coon, professor of biological chemistry who was on the faculty when Nirenberg was studying here.
After graduation, Nirenberg received a fellowship from the American Cancer Society and went to work in the lab of DeWitt Stetten at the National Institutes of Health. In 1960 Nirenberg was appointed to the regular research staff there.
By the late 1950s, Watson and Crick had shown the world the double helix of DNA. Scientists also knew that the sequence of nucleotides in DNA was ultimately responsible for directing the synthesis of all proteins in the cell. And, in very simple terms, it is the protein activity in cells that controls all biological activity.
"An outstanding question of the time was the nature of the genetic code and how it determines the order of incorporation of the 20 different amino acids into the growing chain," notes Robert Greenberg, UM professor emeritus of biological chemistry. It was about this time that Nirenberg and his associate, Heinrich Matthei, began to explore the relationship between DNA in the nucleus, RNA and protein synthesis.
"The pair carried out a bold experiment," says Greenberg. They employed an enzymatically synthesized homopolymer of uridylic acid, one of the four nucleotides of messenger RNA. "That is, instead of adding messenger RNA to a an unpurified preparation of ribosomes (the RNA-protein cpomplexes tat are the cell's protein synthesis factory), they added this synthetic chain of uridylic acid monomers. To their joy, the system exclusively formed large quantities of a new protein-like product -- polyphenylalanine."
Nirenberg with model of DNA molecule
In 1961, Nirenberg delivered a paper about this experiment at an international scientific meeting in Moscow that, at first, got little attention. He reported his success in synthesizing the artificial protein made up of the amino acid phenylalanine. But before the meeting concluded, the significance of his finding led the organizers to invite Nirenberg to present his paper a second time at a special session. In short, Nirenberg had replicated the cellular mechanism that translated the information contained in DNA into a protein, a process mediated by RNA.
With Nirenberg's report, the race was on to determine the precise code of nucleotides in DNA that specified the amino acids to be joined to form any particular protein. Initially, it appeared that researchers other than Nirenberg would be the first to publish the complete genetic code, but with some help from a number of colleagues at the NIH, Nirenberg was able to report many of the corresponding DNA-amino acid code sequences, thereby staking his claim for the Nobel Prize that was awarded in 1968.
Nirenberg shared the Nobel Prize in Medicine that year with Robert Holley of the Salk Institute and Gobind Khorana of MIT, who simultaneously reported important findings to help decipher the genetic code.
Even before the Nobel was awarded, Nirenberg received many honors:
- the National Medal of Science in 1965;
- honorary degrees from Michigan, Yale, the University of Chicago and several other institutions in 1965;
- election to the National Academy of Sciences in 1967.
Today, Nirenberg is Chief of Biomedical Genetics at the National Heart, Lung, and Blood Institute at NIH, where he has continued to work to understand how genetic information controls the development and metabolism of living organisms.
July, 1999
Other links
Nirenberg Biography published by the Nobel Foundation
Background on Protein Synthesis and the Genetic CodeArticle in University Record, July 19, 1999