Marshall W. Nirenberg, who received the 1968 Nobel Prize in Physiology or Medicine for his work on the language of codons and how DNA is translated into proteins, succumbed to cancer at age 82 in his New York home last week (January 15), after several months of illness.

Marshall Nirenberg performing an experiment, circa 1962 Image: Wikimedia commons, MacVicar, National Institutes of Health

"We feel like [we are] losing our close friend who has created the base of the current molecular biology and translational medicine," Akira Kaji of the University of Pennsylvania and Hideko Kaji of Thomas Jefferson University, who both studied protein synthesis at the time of Nirenberg's key discovery and interacted with many researchers in his lab group, wrote in an email to The Scientist. "In our opinion, his contribution is one of the greatest among Nobel laureate[s] who received the prize in physiology and medicine. He discovered common language used throughout the living matter from the simplest virus to the most complicated living matter, human being[s]."

After earning his PhD in biochemistry from the University of Michigan in Ann Arbor, Nirenberg joined the National Institutes of Health (NIH) in 1957, working as a postdoc under Dewitt Stetten, Jr. and became a staff researcher just three years later. In 1962, he became head of the Laboratory of Biochemical Genetics at the NIH's National Heart, Lung, and Blood Institute, and six years later was the first NIH scientist to win a Nobel Prize. He stayed on at the lab for more than 40 years.

Initially, Nirenberg studied sugar transport, glycogen metabolism, and enzyme purification, but he soon decided to change directions to protein synthesis, which he considered to be "one of the most exciting areas in biochemistry" at the time, he wrote in an autobiographical review of his discoveries published in TRENDS in Biochemical Sciences in 2004. He aimed to use a cell-free system to investigate the existence of mRNA and its role in protein synthesis -- a project he knew to be quite risky. "Starting out as an independent investigator you are supposed to hit the deck running and prove that you are an effective, productive investigator," Nirenberg wrote. "On the one hand I wanted to explore an important problem, on the other I was afraid of failure, but the wish to explore was much greater than the fear of failure."

After about a year and a half of working on the project, he welcomed plant physiologist Heinrich Matthei into his lab as a postdoc. Also interested in the mechanism of protein synthesis, Matthei developed a technique to watch protein synthesis in action, involving the incorporation of radioactive amino acids into the protein. It was this assay that allowed the researchers to definitively demonstrate that mRNA existed, was required for protein synthesis, and specifically coded the protein that was to be formed. Furthermore, "this discovery indicated that it may be possible to determine genetic code using [this] in vitro system with synthetic polynucleotides," and spurred "a severe and exciting race to get to the genetic code," said Akira and Hideko Kaji, who still study protein synthesis and related topics nearly 50 years later.

By 1965, with the help of other NIH scientists, Nirenberg was the first to completely decipher the three-base-long sequences known as codons that comprise the cell's vocabulary for protein construction.

Nirenberg's work is "the foundation upon which all subsequent genetic progress rests," NIH Director Francis Collins said in a statement announcing a symposium last November to celebrate the American Chemical Society's designation of the deciphering of the genetic code as a National Historic Chemical Landmark. "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. 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."

Nirenberg shared the 1968 Nobel for his work on the genetic code with Har Gobind Khorana of the University of Wisconsin, who studied nucleic acid synthesis, and Robert Holley of the Salk Institute, who identified the chemical structure of transfer RNA.

"[Nirenberg solved] the problem of [the] genetic code and reading the book of DNA," Murat Kasap, a professor of medical biology and genetics at Kocaeli University in Turkey, wrote in an email to The Scientist. "For this, he should always be remembered."

Correction: The original version of this story stated that Nirenberg was the first federal employee to win a Nobel Prize. In fact, Nirenberg is the first non-presidential federal employee to do so (Theodore Roosevelt won the Nobel Peace Prize in 1906) and the first federal employee to win the Nobel Prize in Physiology or Medicine. The Scientist regrets the error.