A banner reading "UUU are Great Marshall" hung in a hallway.

Molecular Biology Behind the Blackboard

By Paul Theerman

Originally published in Hidden Treasure: The National Library of Medicine, 2011.

The photograph is dramatic, more dramatic in its own way than the famous one of James Watson and Francis Crick. Like that photograph, this one portrays two young scientists in the throes—the joys—of collaboration. The names are not as well known: the young men are Marshall Nirenberg (1927–2010) and Heinrich Matthaei (b. 1929). But their accomplishment was just as important. Watson and Crick worked on molecular reproduction—the DNA molecule formed of two entwined strands, each strand holding the information that guides life’s unfolding, each strand crucial as cells divide. Nirenberg and Matthaei worked on molecular function. For the structure of DNA lent itself to thinking of a “code.” With a pattern of nucleic acid base pairs, A, T, G, and C, laid out to form a strand of DNA, a key was needed to provide meaning—just as Morse code translates dots and dashes into letters and words. In this case the dots and dashes were nucleic acid bases, the letters were amino acids, and the words were proteins, the complex molecules that guide cellular actions such as “break down a sugar,” or “create a cell wall,” or even “make a new molecule of DNA.” Nirenberg and Matthaei cracked that code.

Heinrich Matthaei and Marshall W. Nirenberg
Heinrich Matthaei and Marshall W. Nirenberg working. Photograph is staged from a “behind the blackboard” perspective, 1962.
Profiles in Science

Their approach was simplicity itself (which didn’t make it easy). Make a synthetic nucleic acid, run it through a ribosome (which assembles proteins), and see what comes out. First, put in a strand of all U’s (uracil, a stand-in for T, in this case). Out comes a synthetic molecule made solely of the amino acid phenylalanine, multiple copies joined head-to-tail like a protein. So UUU (the code was formed of three bases) means phenylalanine. Vary the amounts of the nucleic acid bases and see what amino acids join up and in what proportions. Keep it all straight with a chart made of graph paper taped together (dated January 18, 1965, 19 1⁄2 x 19 13⁄16 in. [49.5 x 50.2 cm]) or, actually, many such charts, each a refinement of the last. Work so hard that in a scant four years (starting in 1961 and finishing in 1965) it’s all straight—all the combinations of bases are matched with all twenty amino acids. Three years later, in 1968, pick up a Nobel Prize.

A large paper chart constructed of serveral pages taped together, handwritten in several colors of ink.
Nirenberg’s handwritten genetic code chart, 1965.
Profiles in Science

We don’t mind the staginess of the 1962 eight-by-ten glossy. It flatters us. From our place “behind the blackboard” we see science being made, at least as we like to think it’s made: two men, at the height of their powers, united in a common purpose, working successfully at one of the great challenges of modern biology. The vantage point the photographer provides is pure genius; a more realistic position would put their backs to us or have them looking away from their work. We’re placed in the midst of their creation. We think: “Look, they’re working it out for us!”

The photograph and chart come from the extensive collection of letters, photographs, and laboratory notebooks connected to Nirenberg’s work on the genetic code; other papers deal with his ideas on how the brain works, his next research topic.

The Marshall Nirenberg papers at the National Library of Medicine consist of 159 boxes and oversized materials, 72.5 linear feet. The collection is highlighted in Profiles in Science and has a finding aid.

Paul Theerman, PhD, is Associate Director of the Academy Library and Center for the History of Medicine and Public Health at the New York Academy of Medicine. He was formerly Head of Images and Archives in the History of Medicine Division of the National Library of Medicine.

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