Cracking the Genetic Code
By JudAH GinsBerG
MARSHALL W. NIRENBERG WANTED TO have fun. “If I am going to work this hard,” he recalled recently, “I might just as well have fun — and by fun, I mean I wanted to explore an impor-
tant problem and discover things.”
Nirenberg joined the staff of the National Institutes of Health
(NIH) in 1959, and he needed to find a subject to investigate.
“At that time,” he observed four decades later, “the mechanism
of protein synthesis was incompletely known and messenger
RNA had not been discovered.” Over the decade that fol-
lowed, Nirenberg would become a central contributor to the
deciphering of the genetic code — a scientific accomplish-
ment that was formally recognized by ACS last year (see
box). Nirenberg died January 15, 2010, at the age of 82.
There has been intense interest in the field of protein synthesis since James Watson and Francis Crick used Rosalind
Franklin’s data from X-ray diffraction images of DNA to electrify the scientific world in 1953 with their model of DNA:
the double helix. Watson and Crick’s famous article in Nature
initiated a worldwide quest to discover the genetic code that
translates DNA’s information into proteins.
Nirenberg’s initial goal was to determine whether DNA
(deoxyribonucleic acid) or RNA (ribonucleic acid), copied from
DNA, was the template for protein synthesis. In a famous experiment conducted in 1961, Nirenberg and Heinrich Matthaei,
a postdoctoral fellow from Germany, showed that synthetic
RNA made of a chain of multiple units of uracil (a nucleotide)
instructed a chain of amino acids to add phenylalanine. The
uracil chain, known as poly-U, served as a messenger directing
protein synthesis. The experiment proved that messenger RNA
transcribes genetic information from DNA, directing the assembly of amino acids into complex proteins. The key to breaking
the genetic code — in effect, molecular biology’s Rosetta Stone
— had been discovered.
PHO TOS COURTES Y OF THE NIH NATIONAL LIBRARY OF MEDICINE
After Nirenberg and Matthaei “cracked” the first “word” of
the genetic code, scientists raced to translate the unique code
words for each amino acid in hopes of someday reading the
entire genetic code of living organisms. Nirenberg won this
race, identifying nucleotide combinations for the incorporation
of other amino acids. Nirenberg found that the coding units for
amino acids contain three nucleotides (a triplet). Combining
four nucleotides in three genetic codes yields 64 possible combinations ( 4 x 4 x 4), sufficient to describe 20 amino acids.
In 1964, Nirenberg and Philip Leder, a postdoctoral fellow at
NIH, discovered a way to determine the sequence of the letters
in each triplet word for amino acids. By 1966, Nirenberg had
deciphered the 64 RNA 3-letter code words (codons) for all 20
amino acids. The language of DNA was now understood, and
the code could be expressed in a chart.
Recognizing the Breakthrough
In 1968, Nirenberg won the Nobel Prize in Physiology or
Medicine for his seminal work on the genetic code. He shared
the award with Har Gobind Khorana (University of Wisconsin),
who mastered the synthesis of nucleic acids, and Robert Holley
(Cornell University), who discovered the chemical structure of
transfer-RNA. Collectively, the three were recognized “for their
interpretation of the genetic code and its
function in protein synthesis.” iC
JudAH GinsBerG, a freelance writer and consultant
living in Alexandria, VA, manages the National Historic
Chemical Landmarks Program for the ACS.