Celebrating Marshall Nirenberg

Marshall Nirenberg: A Tribute to “UUU” and to the Man Himself

BY SOMA CHOWDHURY, OD

Marshall Nirenberg, the first NIH intramural scientist to win a Nobel prize, was a “scientist’s scientist” and a “mentor’s mentor,” according to NIH Director Francis Collins. To celebrate the 50th anniversary of Nirenberg’s cracking of the genetic code, the National Library of Medicine (NLM) held “A Tribute to Marshall Nirenberg” on March 17, 2015. The tribute was the first of a trio of events. The second is scheduled for May 20 with David Page from the Whitehead Institute (Cambridge, Massachusetts), 3:00–4:00 p.m., Masur Auditorium (Building 10). The third event is planned for Wednesday, September 30, 3:00–4:00 p.m., in Masur Auditorium (Building 10); Timothy Ley from the McDonnell Genome Institute at Washington University will be the speaker.

The tribute included remarks by friends, family, and colleagues, including Nirenberg’s widow Myrna Weissman and former colleague Frank Portugal, who wrote the book The Least Likely Man: Marshall Nirenberg and the Discovery of the Genetic Code (MIT Press, 2015). In addition, two experts in preserving the Nirenberg materials spoke: George Thoma, chief of NLM’s Communications Engineering Branch, who launched the new Turning-the-Pages interactive presentation of Nirenberg’s work; and David Serlin (University of California, San Diego, in La Jolla), who curated NLM’s Profiles in Science Web site on Nirenberg’s papers. Nirenberg’s Nobel medal and certificate were also presented (by Weissman) to NLM for permanent display in the NLM HIstory of Medicine Division.

The person. “Marshall had the curiosity of a brilliant child,” said Weissman who is a professor of epidemiology and psychiatry at Columbia University College of Physicians and Surgeons (New York). He had “an incredible imagination [and] was a dreamer.” She went on to extol his virtues, adding that he had a complete “lack of arrogance [and] was a most compassionate man.”

Nirenberg was born in New York City and was a regular city kid until he developed rheumatic fever as a teenager, prompting his father to move the family to Orlando, Florida. Soon, young Nirenberg adjusted to the new environment and started getting his hands dirty digging snakes out of their burrows, catching spiders, and exploring the Florida swamps. His master’s thesis (at the University of Florida in Gainesville) on caddisflies reflected his continued fascination with insects and the environment. He continued his studies at the University of Michigan (Ann Arbor, Michigan) and earned a Ph.D. in biochemistry in 1957.

Cracking the code. In 1957, Nirenberg joined NIH as a research fellow at the National Institute of Arthritis, Metabolism, and Digestive Diseases (NIAMDD). He drove all the way from Michigan and upon arriving at NIH at 3:00 a.m., he was delighted to see that Building 10, where he’d be working, was ablaze with lights. “Marshall had found his California garage,” said Weissman, referring to Steve Jobs, who used to work with his father in the garage at their California home.

Nirenberg was somewhat disappointed to learn that the lights were really on for the cleaning crew.

In 1960, after his fellowship ended, Nirenberg became a research biochemist at NIAMDD and conducted independent research on metabolic enzymes. His ideas were brilliant but scientifically and technologically challenging and he knew he might fail. He and his German postdoctoral fellow J. Heinrich Matthaei designed a filter-binding assay experiment to solve what was known as the “poly U puzzle.” He was the first to decode the genetic information contained in RNA and discover that the RNA codon UUU codes for the amino acid L-phenylalanine. Nirenberg shared the 1968 Nobel Prize in Physiology or Medicine for deciphering the genetic code.

“This was first glimpse of the biological Rosetta Stone,” said Collins, who spoke via videotape at the tribute. Nirenberg’s work “sent shock waves through the scientific community. He didn’t stop with cracking the genetic code, but went on to prove it was universal.”

Under-recognized. Compared with renowned scientists of the time such as the American molecular biologist James Watson, the British molecular biologist Francis Crick, and the Russian physicist George Gamow, Nirenberg was unassuming and had a modest scientific background. He was excluded from the prestigious “RNA Tie Club” (each club member wore a tie with one of the 20 amino acids embroidered on it). The neglect didn’t seem to bother him, said Weissman. “In fact, he thought it was kind of funny.”

In the recently published Nirenberg biography, Frank Portugal, who was a postdoctoral fellow in Nirenberg’s lab at NIH, wanted to highlight some of these stories. According to Portugal, either “Marshall’s obscurity as a seminal scientist” or “his extreme modesty” might have contributed to his being unappreciated.

In contrast to the title of the book, “Marshall was the most likely man to unravel the code,” said Weissman.

Beyond genetics: Winning the Nobel prize didn’t alter Nirenberg’s humble personality or his enthusiasm for science. Once he finished with his work on the genetic code, he decided to change fields and shift to neuroscience, which was not surprising given his life pattern of repeatedly stepping outside his comfort zone, both personally and professionally. From Manhattan to rural Orlando, from zoology to biochemistry, and then from genetics to neurobiology, he always pushed his boundaries to explore new things. Working on the hypothesis that there existed a universal code in neurobiology too, Nirenberg soon realized that neuroscience as a field was considerably more complex than genetics. But nevertheless, to him it was the most exciting period of his research life.

Curating memories. From invitation cards to instrument catalogues, from personal photographs to old receipts, Nirenberg kept every piece of paper he ever encountered in his scientific career. David Serlin dug through the enormous pile of papers with the help of his colleagues from NLM (and also Nirenberg himself), uncovering priceless nuggets of scientific history. To make memories of Nirenberg accessible, Serlin created a framework and made deliberate choices on what to preserve for the future. Selected materials are neatly organized into tabs at the Profiles-in-Science Web site (http://profiles.nlm.nih.gov/ps/retrieve/Narrative/JJ/p-nid/21). The site includes such valuable items as scanned copies of Nirenberg’s original handwritten notes, speeches, and drawings of insects, along with personal and professional photographs and other valuable documents. Serlin found “absolute gems” among the hundreds of papers piled high in Nirenberg’s basement and in his home office.

Preserving curated materials is a daunting task. It requires attention to details as minute as knowing the exact type of ballpoint pen used by Nirenberg and his fellows. George Thoma described the process of creating the Turning-the-Pages version of the Marshall Nirenberg Genetic Code Chart, which contain original, handwritten data. Nirenberg and his colleagues meticulously wrote down every detail on large pieces of graph paper and glued them together to create the chart. The boxes are color-coded and represent the deciphered codes translating 64 RNA codons to 20 amino acids. The chart has been scanned in high resolution and digitized, and it is available online as an interactive Web site (http://archive.nlm.nih.gov/proj/ttp/nirenberg/nirenberg-chart11.html). The original chart itself has been stabilized and preserved at the National Library of Medicine using state-of-the-art technology. It is hoped that these resources will preserve Nirenberg’s legacy for future generations of the American public, scientists and nonscientists alike.

More information on the tribute and exhibits can be found at:

• http://circulatingnow.nlm.nih.gov/?s=nirenberg&x=0&y=0
• http://archive.nlm.nih.gov/proj/ttp/nirenberg/nirenberg-chart11.html
• http://profiles.nlm.nih.gov/ps/retrieve/Collection/CID/JJ