Marshall Nirenberg's Work Honored

In May 1961, "Big Science" was grabbing headlines: On May 5, ground crews cheered as Alan Shepard flew high enough to earn the title "First American in Space." Less than three weeks later, on May 25, President John F. Kennedy vowed that the U.S. would put a man on the moon by the end of the decade.

While these events were capturing the nation's imagination, a pair of scientists quietly reached a breathtaking new frontier right here on Earth. In the wee hours of May 27, in Building 10 on the campus of the National Institutes of Health, in Bethesda, Md., researcher Marshall W. Nirenberg and postdoc Heinrich Matthaei found the key to deciphering the genetic code of virtually all life on Earth—a biochemical Rosetta Stone—in a humble test tube. That discovery was recently honored by the American Chemical Society as a National Historic Chemical Landmark.

Nirenberg set out to prove the existence of messenger RNA, which he did, but his experiment yielded much more. He instructed Matthaei to mix 20 samples of synthetic mRNA composed entirely of uracil with a specially prepared cell-free extract of Escherichia coli. For each sample, Matthaei introduced one radiolabeled amino acid and 19 unlabeled amino acids into the extract, varying the "hot" amino acid in each tube.

The sample containing the radiolabeled phenylalanine produced radioactive protein composed entirely of phenylalanine. From these data, Nirenberg concluded that the sequence UUU on mRNA was the genetic code for phenylalanine. This was the first step in determining the genetic instructions for all amino acid synthesis and was also the first demonstration that mRNA, which had been postulated, actually exists.

Within three years, Nirenberg and his colleagues had identified the RNA codons of all 20 standard amino acids that make up proteins. For this work, Nirenberg was one of three winners of the 1968 Nobel Prize in Physiology or Medicine.

Many of Nirenberg's former colleagues and students were on hand as Nirenberg's work became ACS's 64th National Historic Chemical Landmark. Thomas H. Lane, then-ACS president, presented a bronze plaque describing the groundbreaking experiment to Michael Gottesman, NIH's deputy director for intramural research, at the close of a daylong symposium held in Building 10.

The symposium was a tribute to Nirenberg's work and was attended by about 400 people, primarily NIH scientists. Titled "Genes to Proteins: Decoding Genetic Information," the symposium featured presentations of the classical work and cutting-edge research and were punctuated by personal reminiscences. The symposium and landmark ceremony, which together lasted more than five hours, are available in their entirety to view or download at videocast.nih.gov/launch.asp?15434.

Videotaped remarks by NIH Director Francis S. Collins were shown during the symposium and sum up the impact of Nirenberg's work. "It is fair to say that Dr. Nirenberg's discoveries contributed to our completing the human genome, mapping human genetic variation, and studying the correlations between variation and disease," said Collins, who is also the former director of the National Human Genome Research Institute. "One day, when medicine is able to marshal the power of this knowledge to personalize medicine for every individual, the full promise of Nirenberg's work will be realized," he said.

Nirenberg, 82, has spent his entire career at NIH and is the longtime chief of its National Heart, Lung & Blood Institute's Laboratory of Biochemical Genetics. He came to NIH in 1957 as a postdoc working on sugar transport, enzyme purification, and glycogen metabolism. After being hired as an independent researcher in 1959, he made an abrupt change in his research focus that his then-colleague Bruce N. Ames deemed "suicidal." Nirenberg made the move because he wanted to find out whether DNA or RNA directed protein synthesis. Although Nirenberg admitted it was a risky thing for a new researcher to do, he says Ames's opinion "was a little extreme."

The Chemical Society of Washington (the ACS Washington, D.C., local section) sponsored the proposal for the landmark status nearly three years ago. NIH Scientist Emeritus Edwin D. (Ted) Becker, who championed the designation and coorganized the symposium and other events surrounding the landmark designation, says he did so because he "thought it would be particularly important to demonstrate to the public that this work, which sounds like genetics or biology, is really chemistry."