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 assembled a team of about twenty researchers and technicians.
Using the poly-U experiment as a model, Nirenberg and his colleagues identified nucleotide combinations for the incorporation of other amino acids. The researchers found that the coding units for amino acids contain three nucleotides (a triplet). Combining four nucleotides in three-letter codes yielded 64 possible combinations (4 x 4 x 4), sufficient to describe 20 amino acids.
They discovered the codes for other amino acids: for example, AAA for lysine and CCC for proline. Replacing one unit of a triplet code with another nucleotide yielded a different amino acid, for one example, synthetic RNA containing one unit of guanine and two of uracil (code word: GUU) caused incorporation of valine.
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 three-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.
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The Nobel Prize and Reactions
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."
Nirenberg describes the ceremonies surrounding the Nobel as “a week of parties.” Not quite all parties, however, since the rules of the Nobel require recipients to write a review article. This proved a challenge for Nirenberg, who had turned his research attention to neurobiology. ”I found it very difficult,” he later admitted, “to break off from neurobiology and go back to nucleic acids.”
As a Nobel Laureate, Nirenberg received many university offers that included higher salary, more laboratory space, and larger staff. He turned them all down, preferring to spend the rest of his career at NIH. “The reason I stayed,” he says, “was because the thing I had least of was time. I figured that if I went to a university I would use a third of my time to write grants… I thought I could use that time more productively by doing experiments.”
In 1961 The New York Times, echoing President Kennedy, reported that Nirenberg’s research showed that biology “has reached a new frontier.” One journalist suggested the biggest news story of the year was not Russian cosmonaut Yuri Gagarin orbiting the earth but the cracking of the genetic code.
Deciphering the genetic code raised ethical concerns about the potential for genetic engineering. Nirenberg addressed these concerns in a famous editorial in Science in August 1967, noting “that man may be able to program his own cells” before “he has sufficient wisdom to use this knowledge for the benefit of mankind… [D]ecisions concerning the application of this knowledge must be made by society, and only an informed society can make such decisions wisely.” When asked several decades later if society has acted “wisely” regarding genetic engineering, Nirenberg answered, “Absolutely!”
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Landmark Designation and Acknowledgments
Landmark Designation
The American Chemical Society designated the deciphering of the genetic code by Marshall Nirenberg as a National Historic Chemical Landmark at the National Institutes of Health in Bethesda, Maryland, on November 12, 2009. The plaque commemorating the research reads:
In this building, Marshall Nirenberg and Heinrich Matthaei discovered the key to breaking the genetic code when they conducted an experiment using a synthetic RNA chain of multiple units of uracil to instruct a chain of amino acids to add phenylalanine. The uracil (poly-U) served as a messenger directing protein synthesis. This experiment demonstrated that messenger RNA transcribes genetic information from DNA, regulating the assembly of amino acids into complex proteins. Nirenberg would go on to decipher the code by demonstrating the correspondence of various trinucleotides to individual amino acids. He was a co-winner of the Nobel Prize in 1968.
Acknowledgments
Adapted for the internet from “Deciphering the Genetic Code,” produced by the National Historic Chemical Landmarks program of the American Chemical Society in 2009.
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I am an enthusiast and expert in the field of molecular biology and genetic coding. My knowledge is deeply rooted in the historical milestones of deciphering the genetic code, particularly the groundbreaking work led by Marshall Nirenberg. My understanding extends to the intricacies of nucleotide sequences, amino acid incorporation, and the significance of the RNA three-letter code words (codons).
In 1961, Nirenberg and Matthaei embarked on a journey to decode the genetic language, culminating in the identification of the first codon. Following the poly-U experiment, they discovered that amino acids were encoded by specific triplets of nucleotides. This groundbreaking revelation led to the understanding that the coding units for amino acids consisted of three nucleotides, forming a triplet code.
The researchers found 64 possible combinations (4 x 4 x 4) of three-letter codes, sufficient to describe the incorporation of 20 amino acids. Each amino acid was assigned a unique triplet code, such as AAA for lysine and CCC for proline. The replacement of one unit within a triplet code with another nucleotide resulted in the incorporation of a different amino acid. For instance, replacing a unit in the GUU code with a different nucleotide led to the incorporation of valine.
In 1964, Nirenberg, along with Philip Leder, determined the sequence of the letters in each triplet word for amino acids. By 1966, the complete set of 64 RNA three-letter code words (codons) for all 20 amino acids was deciphered. This breakthrough allowed for the expression of the genetic code in a comprehensive chart.
The significance of Nirenberg's work was recognized in 1968 when he was awarded the Nobel Prize in Physiology or Medicine. The Nobel Prize, shared with Har Gobind Khorana and Robert Holley, acknowledged their collective contribution to interpreting the genetic code and its function in protein synthesis.
Nirenberg's commitment to science is further evident in his decision to stay at the National Institutes of Health (NIH) despite lucrative offers from universities. He believed that his time was best spent conducting experiments rather than writing grants.
The ethical implications of deciphering the genetic code were addressed by Nirenberg in a 1967 Science editorial, emphasizing the importance of informed societal decisions regarding genetic engineering. In subsequent years, Nirenberg expressed satisfaction with how society handled the challenges posed by genetic engineering.
The American Chemical Society designated the deciphering of the genetic code as a National Historic Chemical Landmark in 2009. This recognition highlighted the experiment using a synthetic RNA chain to instruct amino acid synthesis, illustrating the role of messenger RNA in transcribing genetic information from DNA.
In conclusion, Marshall Nirenberg's pioneering work in deciphering the genetic code marked a transformative moment in molecular biology, laying the foundation for advancements in genetic engineering and our understanding of the language of DNA.
