RNA Tie Club
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The RNA Tie Club was an informal scientific club, meant partly to be humorous, of select scientists who were interested in how proteins were synthesised from genes, specifically the
genetic code Genetic code is a set of rules used by living cell (biology), cells to Translation (biology), translate information encoded within genetic material (DNA or RNA sequences of nucleotide triplets or codons) into proteins. Translation is accomplished ...
. It was created by
George Gamow George Gamow (sometimes Gammoff; born Georgiy Antonovich Gamov; ; 4 March 1904 – 19 August 1968) was a Soviet and American polymath, theoretical physicist and cosmologist. He was an early advocate and developer of Georges Lemaître's Big Ba ...
upon a suggestion by
James Watson James Dewey Watson (born April 6, 1928) is an American molecular biology, molecular biologist, geneticist, and zoologist. In 1953, he co-authored with Francis Crick the academic paper in ''Nature (journal), Nature'' proposing the Nucleic acid ...
in 1954 when the relationship between nucleic acids and amino acids in
genetic information A nucleic acid sequence is a succession of Nucleobase, bases within the nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. This succession is denoted by a series of a set of five different letters that indicate the orde ...
was unknown. The club consisted of 20 full members, each representing an amino acid, and four honorary members, representing the four
nucleotides Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
. The function of the club members was to think up possible solutions and share with the other members. The first important document of the RNA Tie Club was
Francis Crick Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the Nucleic acid doub ...
's adaptor hypothesis in 1955. Experimental work on the hypothesis led to the discovery of
transfer RNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...
, a molecule that carries the key to genetic code. Most of the theoretical groundwork and preliminary experiments on the genetic code were done by the club members within a decade. However, the specific code was discovered by
Marshall Nirenberg Marshall Warren Nirenberg (April 10, 1927 – January 15, 2010) was an American biochemist and geneticist. He shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" a ...
, a non-member, who received
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...
in 1968 for the discovery.


History


Background

In 1953, English biophysicist
Francis Crick Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the Nucleic acid doub ...
and American biologist
James Watson James Dewey Watson (born April 6, 1928) is an American molecular biology, molecular biologist, geneticist, and zoologist. In 1953, he co-authored with Francis Crick the academic paper in ''Nature (journal), Nature'' proposing the Nucleic acid ...
, working together at the
Cavendish Laboratory The Cavendish Laboratory is the Department of Physics at the University of Cambridge, and is part of the School of Physical Sciences. The laboratory was opened in 1874 on the New Museums Site as a laboratory for experimental physics and is named ...
of the University of Cambridge, deduced the structure of DNA, the principal genetic material of organisms, thought to link genetic information in DNA to proteins. By 1954, it was becoming understood that the genetic information pathway involved
DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
, RNA and proteins. However, the structure and nature of RNA were still a mystery (specific RNA molecules were not known until 1960), especially how RNA is involved in protein synthesis. Watson called this problem "the mystery of life" in his letter to Crick. Soviet-American physicist
George Gamow George Gamow (sometimes Gammoff; born Georgiy Antonovich Gamov; ; 4 March 1904 – 19 August 1968) was a Soviet and American polymath, theoretical physicist and cosmologist. He was an early advocate and developer of Georges Lemaître's Big Ba ...
at
George Washington University The George Washington University (GW or GWU) is a Private university, private University charter#Federal, federally-chartered research university in Washington, D.C., United States. Originally named Columbian College, it was chartered in 1821 by ...
suggested the first scheme for protein synthesis from DNA. In early 1954, he spent several days at Woods Hole on
Cape Cod Cape Cod is a peninsula extending into the Atlantic Ocean from the southeastern corner of Massachusetts, in the northeastern United States. Its historic, maritime character and ample beaches attract heavy tourism during the summer months. The ...
with Crick, Watson and
Sydney Brenner Sydney Brenner (13 January 1927 – 5 April 2019) was a South African biologist. In 2002, he shared the Nobel Prize in Physiology or Medicine with H. Robert Horvitz and Sir John E. Sulston. Brenner made significant contributions to wo ...
, discussing genetics. Based on the Watson-Crick model, he proposed a "direct DNA template hypothesis" stating that proteins are synthesised directly from the double-stranded grooves of DNA. The four bases of DNA were assumed to synthesise 20 different amino acids as triplets with overlapping nucleotide sequences. He published the hypothesis in the 13 February 1954 issue of ''
Nature Nature is an inherent character or constitution, particularly of the Ecosphere (planetary), ecosphere or the universe as a whole. In this general sense nature refers to the Scientific law, laws, elements and phenomenon, phenomena of the physic ...
'', explaining:
It seems to me that such translation procedure can be easily established by considering the ' key-and-lock' relation between various amino-acids, and the rhomb-shaped 'holes' formed by various nucleotides in the deoxyribonucleic acid chain... One can speculate that free amino-acids from the surrounding medium get caught into the 'holes' of deoxyribonucleic acid molecules, and thus unite into the corresponding peptide chains.


Foundation

In May 1954, Watson visited Gamow, who was on sabbatical at the
University of California, Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California), is a Public university, public Land-grant university, land-grant research university in Berkeley, California, United States. Founded in 1868 and named after t ...
. While discussing Gamow's hypothesis, he suggested that they form a 20-member club to work out the genetic code. Gamow instantly came up with the RNA Tie Club to "solve the riddle of the RNA structure and to understand how it built proteins", adding the motto "do or die; or don't try."Lily E. Kay (2000.
''Who Wrote the Book of Life?: A History of the Genetic Code''
Stanford University Press. .
The club thus consisted of 20 eminent scientists, each of whom corresponded to an amino acid, plus four honorary members (S. Brenner, VAL. F. Lipmann, A. Szent-Gyorgyi, and another individual), one for each
nucleotide Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
. Each member received a woolen necktie having an embroidered helix, hence the name "RNA Tie Club".


Members


The tie and tiepin

Members of the RNA Tie Club received a black wool-knit tie with a green and yellow RNA helix emblazoned on it. The original design of the tie came from Orgel, with the final pattern re-imagined by Gamow. Gamow's tie pattern was delivered to a Los Angeles haberdasher on Colorado Avenue by Watson, with the shop tailor promising to make the ties for $4 each. Along with each tie, members of the club were to receive a golden tiepin with the three letter abbreviation of their club amino acid designation. Not all members may have received their pin. Gamow, however, wore his pin on several occasions, often causing confusion and questioning of why he was wearing the "wrong initials".


Successes

The RNA Tie Club never had a formal meeting of all its members. Members visited each other to discuss the scientific developments, usually involving cigars and alcohol. This allowed bonding and close friendships to develop among this scientific elite, and it turned out to be a breeding ground for creative ideas. The members mailed letters and preprints of articles to each other suggesting new concepts and ideas.Friedberg, Errol C: ''The Writing Life of James D. Watson'', Cold Spring Harbor Laboratory Press, September 2004.


Number of nucleotides in a codon

Using mathematics, Gamow postulated that a nucleotide code consisting of three letters (triplets) would be enough to define all 20 amino acids. This concept is the basis of "
codons Genetic code is a set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets or codons) into proteins. Translation is accomplished by the ribosome, which links pro ...
", and set an upper and lower limit on their size. Gamow had simply estimated that the number of bases and their complementary pairs in a DNA strand could create 20 cavities for amino acids, meaning that 20 different amino acids could be involved in protein synthesis. He named this DNA–protein interaction the "diamond code." Although Gamow's premise that DNA directly synthesized proteins was proven wrong, the triplet code became the foundation of genetic code.


Codons

Sydney Brenner proposed the concept of the codon, the idea that three non-overlapping nucleotides could code for one amino acid.Brenner, Sydney: ''On the Impossibility of All Overlapping Triplet Codes'', 1956,
later published in PNAS: PNAS USA. 1957 August 15; 43(8): 687–694.
His proof involved statistics and experimental evidence from amino acid protein sequences.


Adaptor hypothesis

Francis Crick proposed the " adaptor hypothesis" (a name given by Brenner) suggesting that some molecule ferried the amino acids around, and put them in the correct order corresponding to the nucleic acid sequence.Crick, Francis, and Brenner, Sydney: ''Some Footnotes on Protein Synthesis: A Note for the RNA Tie Club.'' December 1959. The hypothesis contradicted Gamow's direct DNA template hypothesis, positing that DNA could not synthesise proteins directly, but instead requires other molecules, adaptors to convert the DNA sequences to amino acid sequences. He also suggested that there were such 20 separate adaptor molecules.Crick, Francis: ''From DNA to protein On degenerate templates and the adapter hypothesis: a note for the RNA Tie Club'', 1955.Crick, Francis: ''What Mad Pursuit'' 1988, pg 95-96. This was later confirmed by Robert Holley and the adaptor molecules were named
transfer RNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...
s (tRNAs). The typed paper distributed to the members of the RNA Tie Club in January 1955 as "On Degenerate Templates and the Adaptor Hypothesis: A Note for the RNA Tie Club" is described as "one of the most important unpublished articles in the history of science", and "the most famous unpublished paper in the annals of molecular biology." Watson recalled, "The most famous of these npublishednotes, by Francis, in time would totally change the way we thought about protein synthesis.


Personal successes

Six members of the RNA Tie Club became Nobel laureates: Richard Feynman, Melvin Calvin, James Watson, Max Delbruck, Francis Crick and Sydney Brenner. However, the ultimate goal of understanding and deciphering the code linking nucleic acids and amino acids was achieved by
Marshall Nirenberg Marshall Warren Nirenberg (April 10, 1927 – January 15, 2010) was an American biochemist and geneticist. He shared a Nobel Prize in Physiology or Medicine in 1968 with Har Gobind Khorana and Robert W. Holley for "breaking the genetic code" a ...
, who was not a member of the RNA Tie Club,Everson, Ted: ''The gene: a historical perspective'', pg 90-91. and received the Nobel Prize in Physiology or Medicine in 1968 with Holley and Har Gobind Khorana.


References

{{reflist Genetics-related lists History of genetics Lists of scientists by membership Chemistry societies Biology societies