Editing Francis Crick (section)

===Molecular biology===
In 1954, at the age of 37, Crick completed his PhD thesis: "''X-Ray Diffraction: Polypeptides and Proteins''" and received his degree. Crick then worked in the laboratory of [[David Harker]] at [[Polytechnic University of New York|Brooklyn Polytechnic Institute]], where he continued to develop his skills in the analysis of [[X-ray crystallography|X-ray diffraction]] data for proteins, working primarily on [[ribonuclease]] and the mechanisms of [[protein synthesis]]. David Harker, the American X-ray crystallographer, was described as "the John Wayne of crystallography" by Vittorio Luzzati, a crystallographer at the Centre for Molecular Genetics in Gif-sur-Yvette near Paris, who had worked with Rosalind Franklin.{{citation needed|date=March 2015}}

After the discovery of the double helix model of DNA, Crick's interests quickly turned to the biological implications of the structure. In 1953, Watson and Crick published another article in ''Nature'' which stated: "it therefore seems likely that the precise sequence of the bases is the code that carries the genetical information".<ref>{{Cite journal|vauthors=Watson JD, Crick FH |title=Genetical implications of the structure of deoxyribonucleic acid |journal=Nature |volume=171 |issue=4361 |pages=964–7 |date=May 1953 |pmid=13063483 |doi= 10.1038/171964b0|url= https://profiles.nlm.nih.gov/SC/B/B/Y/X/_/scbbyx.pdf |archive-url=https://web.archive.org/web/20050912214219/http://profiles.nlm.nih.gov/SC/B/B/Y/X/_/scbbyx.pdf |archive-date=2005-09-12 |url-status=live |format=PDF reprint|bibcode = 1953Natur.171..964W |s2cid=4256010 }}</ref>

[[File:Collagentriplehelix.png|thumb|left|99px|Collagen triple helix.]]

In 1956, Crick and Watson speculated on the structure of small viruses. They suggested that spherical viruses such as [[Tomato bushy stunt virus]] had icosahedral symmetry and were made from 60 identical subunits.<ref>{{Cite journal|author=Morgan GJ |title=Historical review: viruses, crystals and geodesic domes |journal=Trends in Biochemical Sciences |volume=28 |issue=2 |pages=86–90 |date=February 2003 |pmid=12575996 |doi=10.1016/S0968-0004(02)00007-5|doi-access=free }}</ref>

After his short time in New York, Crick returned to Cambridge where he worked until 1976, at which time he moved to California. Crick engaged in several X-ray diffraction collaborations such as one with [[Alexander Rich]] on the structure of [[collagen]].<ref>{{Cite journal|vauthors=Rich A, Crick FH |title=The structure of collagen |journal=Nature |volume=176 |issue=4489 |pages=915–6 |date=November 1955 |pmid=13272717 |doi= 10.1038/176915a0|url=https://profiles.nlm.nih.gov/SC/B/B/Z/L/_/scbbzl.pdf |archive-url=https://web.archive.org/web/20050912214247/http://profiles.nlm.nih.gov/SC/B/B/Z/L/_/scbbzl.pdf |archive-date=2005-09-12 |url-status=live |format=PDF reprint|bibcode = 1955Natur.176..915R |s2cid=9611917 }}</ref> However, Crick was quickly drifting away from continued work related to his expertise in the interpretation of X-ray diffraction patterns of proteins.

[[George Gamow]] established a group of scientists interested in the role of [[RNA]] as an intermediary between DNA as the genetic storage molecule in the [[nucleus (cell)|nucleus]] of cells and the synthesis of proteins in the [[cytoplasm]] (the [[RNA Tie Club]]). It was clear to Crick that there had to be a code by which a short sequence of nucleotides would specify a particular [[amino acid]] in a newly synthesised protein. In 1956, Crick wrote an informal paper about the [[genetic code|genetic coding]] problem for the small group of scientists in Gamow's RNA group.<ref>"[https://profiles.nlm.nih.gov/SC/B/B/G/F/_/scbbgf.pdf On Degenerate Templates and the Adaptor Hypothesis: A Note for the RNA Tie Club]" by Francis Crick (1956).</ref> In this article, Crick reviewed the evidence supporting the idea that there was a common set of about 20 amino acids used to synthesise proteins. Crick proposed that there was a corresponding set of small "adaptor molecules" that would [[hydrogen bond]] to short sequences of a nucleic acid, and also link to one of the amino acids. He also explored the many theoretical possibilities by which short nucleic acid sequences might code for the 20 amino acids.

[[File:3d tRNA.png|thumb|right|Molecular model of a [[tRNA]] molecule.{{citation needed|date=October 2011}} Crick predicted that such adaptor molecules might exist as the links between [[codon]]s and [[amino acid]]s.]]
During the mid-to-late 1950s Crick was very much intellectually engaged in sorting out the mystery of how proteins are synthesised. By 1958, Crick's thinking had matured and he could list in an orderly way all of the key features of the protein synthesis process:<ref name="auto"/>
* genetic information stored in the sequence of DNA molecules
* a "messenger" RNA molecule to carry the instructions for making one protein to the cytoplasm
* adaptor molecules ("they might contain nucleotides") to match short sequences of nucleotides in the RNA messenger molecules to specific amino acids
* ribonucleic-protein complexes that catalyse the assembly of amino acids into proteins according to the messenger RNA

The adaptor molecules were eventually shown to be [[tRNA]]s and the catalytic "ribonucleic-protein complexes" became known as [[ribosome]]s. An important step was the realisation by Crick and Brenner on 15 April 1960 during a conversation with [[François Jacob]] that [[messenger RNA]] was not the same thing as [[ribosomal RNA]].<ref name="Cobb">{{cite journal |author-link1=Matthew Cobb |vauthors=Cobb M |date=29 June 2015 |title=Who discovered messenger RNA? |journal=Current Biology |volume=25 |issue=13 |pages=R526–R532 |doi=10.1016/j.cub.2015.05.032 |pmid=26126273 |doi-access=free|bibcode=2015CBio...25.R526C }}</ref>  Later that summer, Brenner, Jacob, and [[Matthew Meselson]] conducted an experiment which was the first to prove the existence of messenger RNA.<ref name="Cobb" />  None of this, however, answered the fundamental theoretical question of the exact nature of the genetic code. In his 1958 article, Crick speculated, as had others, that a triplet of nucleotides could code for an amino acid. Such a code might be "degenerate", with 4×4×4=64 possible triplets of the four nucleotide subunits while there were only 20 amino acids. Some amino acids might have multiple triplet codes. Crick also explored other codes in which, for various reasons, only some of the triplets were used, "magically" producing just the 20 needed combinations.<ref>{{cite journal|last1=Hayes|first1=Brian|journal=American Scientist|year=1998|access-date=11 January 2017|url=http://www.americanscientist.org/issues/pub/the-invention-of-the-genetic-code|title=The Invention of the Genetic Code|volume=86|pages=8|doi=10.1511/1998.17.3338|s2cid=121907709 }}</ref> Experimental results were needed; theory alone could not decide the nature of the code. Crick also used the term "[[central dogma of molecular biology|central dogma]]" to summarise an idea that implies that genetic information flow between macromolecules would be essentially one-way:

:'''DNA → RNA → protein'''

Some critics thought that by using the word "dogma", Crick was implying that this was a rule that could not be questioned, but all he really meant was that it was a compelling idea without much solid evidence to support it. In his thinking about the biological processes linking DNA genes to proteins, Crick made explicit the distinction between the materials involved, the energy required, and the information flow. Crick was focused on this third component (information) and it became the organising principle of what became known as molecular biology. Crick had by this time become a highly influential theoretical molecular biologist.

Proof that the genetic code is a degenerate triplet code finally came from genetics experiments, some of which were performed by Crick.<ref>{{Cite journal|vauthors=Crick FH, Barnett L, Brenner S, Watts-Tobin RJ |title=General nature of the genetic code for proteins |journal=Nature |volume=192 |issue= 4809|pages=1227–32 |date=December 1961 |pmid=13882203 |doi= 10.1038/1921227a0|url=https://profiles.nlm.nih.gov/SC/B/C/B/J/_/scbcbj.pdf |archive-url=https://web.archive.org/web/20050912214328/http://profiles.nlm.nih.gov/SC/B/C/B/J/_/scbcbj.pdf |archive-date=2005-09-12 |url-status=live |format=PDF reprint|bibcode = 1961Natur.192.1227C |s2cid=4276146 }}</ref> The details of the code came mostly from work by [[Marshall Warren Nirenberg|Marshall Nirenberg]] and others who synthesized synthetic RNA molecules and used them as templates for ''[[in vitro]]'' protein synthesis.<ref>{{Cite journal|author=Crick FH |title=The Croonian lecture, 1966. The genetic code |journal=Proc. R. Soc. Lond. B Biol. Sci. |volume=167 |issue=9 |pages=331–47 |year=1967 |pmid=4382798 |doi= 10.1098/rspb.1967.0031|url= https://profiles.nlm.nih.gov/SC/B/C/B/X/_/scbcbx.pdf |archive-url=https://web.archive.org/web/20050912214319/http://profiles.nlm.nih.gov/SC/B/C/B/X/_/scbcbx.pdf |archive-date=2005-09-12 |url-status=live |format=PDF reprint|bibcode = 1967RSPSB.167..331C |s2cid=11131727 }}</ref> Nirenberg first announced his results to a small audience in Moscow at a 1961 conference. Crick's reaction was to invite Nirenberg to deliver his talk to a larger audience.<ref name=NautilusGoldstein>{{cite web |url=https://nautil.us/issue/72/quandary/the-thrill-of-defeat-rp |title=The Thrill of Defeat: What Francis Crick and Sydney Brenner taught me about being scooped |last=Goldstein |first=Bob |date=30 May 2019 |publisher=Nautilus |access-date=21 January 2021 |archive-date=10 December 2021 |archive-url=https://web.archive.org/web/20211210101407/https://nautil.us/issue/72/quandary/the-thrill-of-defeat-rp |url-status=dead }}</ref>