Editing Linus Pauling (section)

== Career ==
{{external media |width=190px | float = right | headerimage= [[File:Sickle Cell Blood Smear.JPG|170px]] | video1 = [http://watch.opb.org/video/1954582651/ ''Linus Pauling''], Oregon Experience, [[Oregon Historical Society]]}}In 1926, Pauling was awarded a [[Guggenheim Fellowship]] to travel to Europe, to study under German physicist [[Arnold Sommerfeld]] in Munich, Danish physicist [[Niels Bohr]] in Copenhagen and Austrian physicist [[Erwin Schrödinger]] in [[Zürich]]. All three were experts in the new field of [[quantum mechanics]] and other branches of physics.<ref name="Guggenheim" /> Pauling became interested in how quantum mechanics might be applied in his chosen field of interest, the [[Electron configuration|electronic structure]] of atoms and molecules. In Zürich, Pauling was also exposed to one of the first quantum mechanical analyses of bonding in the [[hydrogen]] molecule, done by [[Walter Heitler]] and [[Fritz London]].<ref name="Realism">{{Cite conference |date=December 9, 2010 |orig-date=1996-10-31 |title=Realism and anti-realism in the philosophy of science |url={{GBurl|id=mvYIkgAACAAJ|page=161}} |conference=Beijing International Conference 1992 |location=[[Dordrecht]] |publisher=[[Springer Nature|Springer]] |page=161 |isbn=978-90-481-4493-8 |ol=28281917M |access-date=May 27, 2015 |editor1-last=Cohen |editor1-first=Robert S. |editor2-last=Hilpinen |editor2-first=Risto |editor3-last=Qiu |editor3-first=Ren-Zong}}</ref> Pauling devoted the two years of his European trip to this work and decided to make it the focus of his future research. He became one of the first scientists in the field of quantum chemistry and a pioneer in the application of quantum theory to the structure of molecules.<ref name="PNNL">{{Cite web |title=About Linus Pauling |url=https://www.pnnl.gov/projects/linus-pauling-distinguished-postdoctoral-fellowship/about |url-status=live |archive-url=https://web.archive.org/web/20220302175453/https://www.pnnl.gov/projects/linus-pauling-distinguished-postdoctoral-fellowship/about |archive-date=March 2, 2022 |access-date=April 13, 2022 |website=[[Pacific Northwest National Laboratory]] |language=en}}</ref>

In 1927, Pauling took a new position as an assistant professor at [[Caltech]] in [[theoretical chemistry]].<ref name="OH">{{Cite book |last=Pauling |first=Linus |url=https://digital.sciencehistory.org/works/5h73px42w |title=Oral history interview with Linus C. Pauling |date=April 6, 1987 |publisher=[[Science History Institute]] |location=[[Denver]] |publication-place=[[Philadelphia]] |language=en |author-mask=4 |access-date=April 13, 2022 |archive-url=https://web.archive.org/web/20210816110527/https://digital.sciencehistory.org/works/5h73px42w |archive-date=August 16, 2021 |url-status=live |interviewer-last=Sturchio |interviewer-first=Jeffrey L.}}</ref> He launched his faculty career with a very productive five years, continuing with his [[X-ray]] crystal studies and also performing quantum mechanical calculations on atoms and molecules. He published approximately fifty papers in those five years, and created the five rules now known as [[Pauling's rules]].<ref>{{Cite journal |last=Pauling |first=Linus |author-mask=4 |date=April 1, 1929 |title=The principles determining the structure of complex ionic crystals |journal=[[Journal of the American Chemical Society]] |volume=51 |issue=4 |pages=1010–1026 |doi=10.1021/ja01379a006|bibcode=1929JAChS..51.1010P }}</ref><ref name="Pauling1960">{{Cite book |last=Pauling |first=Linus |url={{GBurl|id=L-1K9HmKmUUC}} |title=The nature of the chemical bond and the structure of molecules and crystals; an introduction to modern structural chemistry |date=January 31, 1960 |publisher=[[Cornell University Press]] |isbn=978-0-8014-0333-0 |edition=3rd |location=[[Ithaca, New York]] |pages=543–562 |ol=26811428M |author-mask=4 |orig-date=1939}}</ref> By 1929, he was promoted to associate professor, and by 1930, to full professor.<ref name="OH" /> In 1931, the [[American Chemical Society]] awarded Pauling the Langmuir Prize for the most significant work in pure science by a person 30 years of age or younger.<ref>{{Cite web |last=Hager |first=Thomas |author-link=Thomas Hager |date=December 2004 |title=The Langmuir Prize |url=http://scarc.library.oregonstate.edu/coll/pauling/bond/narrative/page28.html |url-status=live |archive-url=https://web.archive.org/web/20201212140745/http://scarc.library.oregonstate.edu/coll/pauling/bond/narrative/page28.html |archive-date=December 12, 2020 |access-date=February 29, 2008 |website=[[Oregon State University]] |language=en}}</ref> The following year, Pauling published what he regarded as his most important paper, in which he first laid out the concept of [[Orbital hybridization|hybridization of atomic orbitals]] and analyzed the [[tetravalence|tetravalency]] of the [[carbon]] atom.<ref>{{Cite journal |last=Pauling |first=Linus |author-mask=4 |date=March 1, 1932 |title=The nature of the chemical bond. III. The transition from one extreme bond type to another |journal=[[Journal of the American Chemical Society]] |volume=54 |issue=3 |pages=988–1003 |doi=10.1021/ja01342a022|bibcode=1932JAChS..54..988P }}</ref>

At Caltech, Pauling struck up a close friendship with [[Theoretical physics|theoretical physicist]] [[Robert Oppenheimer]] at the [[University of California, Berkeley]], who spent part of his research and teaching schedule as a visitor at Caltech each year.<ref name="Nature" /><ref name="Oppenheimer">{{Cite book |last=Monk |first=Ray |url={{GBurl|id=EkJ9aWTjWjUC|page=203}} |title=Robert Oppenheimer : a life inside the center |date=March 11, 2014 |publisher=[[Anchor Books]] |isbn=978-0-385-72204-9 |edition=First Anchor Books |page=203 |ol=32935915M |author-link=Ray Monk |orig-date=2012}}</ref> Pauling was also affiliated with Berkeley, serving as a visiting lecturer in physics and chemistry from 1929 to 1934.<ref>{{Cite web |title=Early Career at the California Institute of Technology (1927–1930) |url=http://scarc.library.oregonstate.edu/coll/pauling/chronology/page10.html |url-status=live |archive-url=https://web.archive.org/web/20211112063521/http://scarc.library.oregonstate.edu/coll/pauling/chronology/page10.html |archive-date=November 12, 2021 |access-date=May 18, 2017 |website=[[Oregon State University]] |language=en}}</ref> Oppenheimer even gave Pauling a stunning personal collection of minerals.<ref name="LostAlly">{{Cite web |title=A Lost Ally |url=http://scarc.library.oregonstate.edu/coll/pauling/bond/narrative/page20.html |url-status=live |archive-url=https://web.archive.org/web/20210820230846/http://scarc.library.oregonstate.edu/coll/pauling/bond/narrative/page20.html |archive-date=August 20, 2021 |access-date=May 27, 2015 |website=[[Oregon State University]] |language=en}}</ref>  The two men planned to mount a joint attack on the nature of the chemical bond: apparently Oppenheimer would supply the mathematics and Pauling would interpret the results. Their relationship soured when Oppenheimer tried to pursue Pauling's wife, Ava Helen. When Pauling was at work, Oppenheimer came to their home and blurted out an invitation to Ava Helen to join him on a tryst in Mexico. She flatly refused, and reported the incident to Pauling. He immediately cut off his relationship with Oppenheimer.{{r|Nature|p=152}}<ref name="Oppenheimer" />

In the summer of 1930, Pauling made another European trip, during which he learned about gas-phase electron [[diffraction]] from [[Herman Francis Mark]]. After returning, he built an [[electron diffraction]] instrument at Caltech with a student of his, [[Lawrence O. Brockway|Lawrence Olin Brockway]], and used it to study the [[molecular geometry|molecular structure]] of a large number of chemical substances.<ref name="Hargittai">{{Cite book |last1=Hargittai |first1=István |url={{GBurl|id=KPqac4Y551AC|page=134}} |title=In our own image: personal symmetry in discovery |last2=Hargittai |first2=Magdolna |date=February 29, 2000 |publisher=[[Springer Nature]] |isbn=978-0-306-46091-3 |location=New York City |language=en |lccn=99033173 |ol=9669915M |access-date=May 27, 2015}}</ref>

Pauling introduced the concept of [[electronegativity]] in 1932.<ref name="paulingJACS">{{Cite journal |last=Pauling |first=L. |author-mask=4 |date=September 1, 1932 |title=The Nature of the Chemical Bond. IV. The Energy of Single Bonds and the Relative Electronegativity of Atoms |journal=[[Journal of the American Chemical Society]] |volume=54 |issue=9 |pages=3570–3582 |doi=10.1021/ja01348a011 |bibcode=1932JAChS..54.3570P |issn=0002-7863 |lccn=16003159 |oclc=01226990}}</ref> Using the various properties of molecules, such as the energy required to break bonds and the [[dipole]] [[Moment (physics)|moments]] of molecules, he established a scale and an associated numerical value for most of the elements{{thinsp|—}}the [[Pauling scale of electronegativity|Pauling Electronegativity Scale]]{{thinsp|—}}which is useful in predicting the nature of bonds between atoms in molecules.<ref name="Scale2">{{Cite web |date=March 17, 2009 |title=The Pauling Electronegativity Scale: Part 2, Inspired by Biology |url=https://paulingblog.wordpress.com/2009/03/17/the-pauling-electronegativity-scale-part-2-inspired-by-biology/ |url-status=live |archive-url=https://web.archive.org/web/20211117185840/https://paulingblog.wordpress.com/2009/03/17/the-pauling-electronegativity-scale-part-2-inspired-by-biology/ |archive-date=November 17, 2021 |access-date=March 17, 2009 |website=[[Oregon State University]] |language=en}}</ref>

In 1936, Pauling was promoted to chairman of the division of chemistry and chemical engineering at Caltech, and to the position of director of the Gates and Crellin Laboratories of Chemistry. He would hold both positions until 1958.<ref name="OH" /> Pauling also spent a year in 1948 at the [[University of Oxford]] as George Eastman Visiting Professor and Fellow of Balliol.<ref>{{Cite web |date=August 21, 1994 |title=Obituary: Professor Linus Pauling |url=https://www.independent.co.uk/news/people/obituary-professor-linus-pauling-1377923.html |url-status=live |archive-url=https://web.archive.org/web/20210616040502/https://www.independent.co.uk/news/people/obituary-professor-linus-pauling-1377923.html |archive-date=June 16, 2021 |access-date=January 25, 2018 |website=[[The Independent]] |language=en}}</ref>

===Nature of the chemical bond===
[[File:Linus Pauling 1955a.jpg|thumb|Linus Pauling with an inset of his Nobel Prize in 1955]]

In the late 1920s, Pauling began publishing papers on the nature of the [[chemical bond]]. Between 1937 and 1938, he took a position as George Fischer Baker Non-Resident Lecturer in Chemistry at [[Cornell University]]. While at Cornell, he delivered a series of nineteen lectures<ref>{{Cite web |title=Outline of the George Fischer Baker Lectureship, Cornell University |url=http://scarc.library.oregonstate.edu/coll/pauling/bond/notes/1937s.3-outline-01-large.html |url-status=live |archive-url=https://web.archive.org/web/20211112063624/http://scarc.library.oregonstate.edu/coll/pauling/bond/notes/1937s.3-outline-01-large.html |archive-date=November 12, 2021 |access-date=April 13, 2022 |website=[[Oregon State University]] |language=en}}</ref> and completed the bulk of his famous textbook ''The Nature of the Chemical Bond''.<ref name="The George Fischer Baker Lectureship and the Beginnings of the Manuscript">{{Cite web |date=July 30, 2014 |title=The George Fischer Baker Lectureship and the Beginnings of the Manuscript |url=https://paulingblog.wordpress.com/2014/07/30/the-george-fischer-baker-lectureship-and-the-beginnings-of-the-manuscript/ |url-status=live |archive-url=https://web.archive.org/web/20220307085556/https://paulingblog.wordpress.com/2014/07/30/the-george-fischer-baker-lectureship-and-the-beginnings-of-the-manuscript/ |archive-date=March 7, 2022 |access-date=June 3, 2015 |website=The Pauling Blog |publisher=[[Oregon State University]] |language=en}}</ref><ref name="Pauling1960" />{{rp|Preface}} It is based primarily on his work in this area that he received the [[Nobel Prize in Chemistry]] in 1954 "for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances".<ref name="Nobel" /> Pauling's book has been considered "chemistry's most influential book of this century and its effective bible".<ref name="Genes2001">{{Cite book |last=Watson |first=James D. |url=https://archive.org/details/passionfordnagen0000wats |title=A passion for DNA: genes, genomes, and society |date=2001 |publisher=[[Oxford University Press]] |isbn=978-0-19-860428-0 |edition=2003 |location=[[Oxford]] |ol=7401431M |author-link=James Watson |via=[[Internet Archive]]}}</ref> In the 30 years after its first edition was published in 1939, the book was cited more than 16,000 times. Even today, many modern scientific papers and articles in important journals cite this work, more than seventy years after the first publication.<ref name="Google">{{Cite web |title=The nature of the chemical bond (citations and estimated counts) |url=https://scholar.google.com/citations?view_op=view_citation&hl=en&user=b0B12YAAAAAJ&citation_for_view=b0B12YAAAAAJ:j5aT6aphRxQC |access-date=May 27, 2015 |website=Google Scholar}}</ref>

Part of Pauling's work on the nature of the chemical bond led to his introduction of the concept of [[orbital hybridization]].<ref>{{Cite web |last=Pauling |first=Linus |year=1928 |title=London's paper. General ideas on bonds |url=http://scarc.library.oregonstate.edu/coll/pauling/bond/notes/sci3.001.21.html |access-date=June 2, 2015 |publisher=Oregon State University Libraries Special Collections}}</ref> While it is normal to think of the electrons in an atom as being described by [[atomic orbital|orbital]]s of types such as ''s'' and ''p'', it turns out that in describing the bonding in molecules, it is better to construct functions that partake of some of the properties of each. Thus the one 2s and three 2p orbitals in a carbon atom can be (mathematically) 'mixed' or combined to make four equivalent orbitals (called sp<sup>3</sup> hybrid orbitals), which would be the appropriate orbitals to describe carbon compounds such as [[methane]], or the 2s orbital may be combined with two of the 2p orbitals to make three equivalent orbitals (called sp{{sup|2}} hybrid orbitals), with the remaining 2p orbital unhybridized, which would be the appropriate orbitals to describe certain [[alkene|unsaturated]] carbon compounds such as [[ethylene]].{{r|Pauling1960|pages=111–120}} Other hybridization schemes are also found in other types of molecules.
Another area which he explored was the relationship between [[ionic bond]]ing, where electrons are transferred between atoms, and [[covalent bond]]ing, where electrons are shared between atoms on an equal basis. Pauling showed that these were merely extremes, and that for most actual cases of bonding, the [[Introduction to quantum mechanics|quantum-mechanical]] [[wave function]] for a polar molecule AB is a [[linear combination|combination]] of wave functions for covalent and ionic molecules.{{r|Pauling1960|page=66}} Here Pauling's ''[[electronegativity]]'' concept is particularly useful; the electronegativity difference between a pair of atoms will be the surest predictor of the degree of ionicity of the bond.<ref>{{Cite web |last=Pauling |first=Linus |date=1930s |title=Notes and Calculations re: Electronegativity and the Electronegativity Scale |url=http://scarc.library.oregonstate.edu/coll/pauling/bond/notes/sci5.001.14.html |access-date=February 29, 2008 |publisher=Oregon State University Libraries Special Collections}}</ref>

The third of the topics that Pauling attacked under the overall heading of "the nature of the chemical bond" was the accounting of the structure of [[aromatic hydrocarbon]]s, particularly the prototype, [[benzene]].<ref>{{Cite web |last=Pauling |first=Linus |date=January 6, 1934 |title=Benzene |url=http://scarc.library.oregonstate.edu/coll/pauling/bond/notes/sci2.004.6.html |access-date=February 29, 2008 |publisher=Oregon State University Libraries Special Collections}}</ref> The best description of benzene had been made by the German chemist [[Friedrich August Kekulé von Stradonitz|Friedrich Kekulé]]. He had treated it as a rapid interconversion between two structures, each with alternating single and [[double bond]]s, but with the double bonds of one structure in the locations where the single bonds were in the other. Pauling showed that a proper description based on quantum mechanics was an intermediate structure which was a blend of each. The structure was a superposition of structures rather than a rapid interconversion between them. The name "[[resonance (chemistry)|resonance]]" was later applied to this phenomenon.<ref>{{Cite web |last=Pauling |first=Linus |date=July 29, 1946 |title=Resonance |url=http://scarc.library.oregonstate.edu/coll/pauling/bond/notes/1946a.3.html |access-date=February 29, 2008 |publisher=Oregon State University Libraries Special Collections}}</ref> In a sense, this phenomenon resembles those of hybridization and also polar bonding, both described above, because all three phenomena involve combining more than one electronic structure to achieve an intermediate result.{{citation needed|date=August 2023}}

===Ionic crystal structures===
In 1929, Pauling published [[Pauling's rules|five rules]] which help to [[crystal structure prediction|predict]] and explain [[crystal structure]]s of [[ionic compound]]s.<ref>{{Cite journal |last=Pauling, Linus |author-link=Pauling L |year=1929 |title=The principles determining the structure of complex ionic crystals |journal=J. Am. Chem. Soc. |volume=51 |issue=4 |pages=1010–1026 |doi=10.1021/ja01379a006|bibcode=1929JAChS..51.1010P }}</ref><ref name=Pauling1960/> 
These rules concern (1) the ratio of cation radius to anion radius, (2) the electrostatic bond strength, (3) the sharing of polyhedron corners, edges and faces, (4) crystals containing different cations, and (5) the rule of parsimony.{{citation needed|date=August 2023}}

===Biological molecules===
[[File:Linus Pauling 1941.png|thumb|Pauling in 1941]]
[[Image:Helix electron density myoglobin 2nrl 17-32.jpg|thumb|upright|An alpha helix in ultra-high-resolution electron density contours, with O atoms in red, N atoms in blue, and hydrogen bonds as green dotted lines (PDB file 2NRL, 17–32)]]

In the mid-1930s, Pauling, strongly influenced by the biologically oriented funding priorities of the Rockefeller Foundation's [[Warren Weaver]], decided to strike out into new areas of interest.<ref name="Kay">{{Cite book |last=Kay |first=Lily E. |url=https://books.google.com/books?id=vEHeNI2a8OEC&pg=PA148 |title=The molecular vision of life: Caltech, the Rockefeller Foundation, and the rise of the new biology |date=1996 |publisher=Oxford University Press |isbn=978-0-19-511143-9 |location=New York [u.a.] |pages=148–151 |access-date=May 27, 2015}}</ref> Although Pauling's early interest had focused almost exclusively on inorganic molecular structures, he had occasionally thought about molecules of biological importance, in part because of Caltech's growing strength in biology. Pauling interacted with such great biologists as [[Thomas Hunt Morgan]], [[Theodosius Dobzhanski]], [[Calvin Bridges]] and [[Alfred Sturtevant]].<ref name="Califano">{{Cite book |last=Califano |first=Salvatore |url=https://books.google.com/books?id=s-sCt4RT0bMC&pg=PA198 |title=Pathways to modern chemical physics |date=2012 |publisher=Springer |isbn=978-3-642-28179-2 |location=Heidelberg [Germany] |page=198 |access-date=May 27, 2015}}</ref> His early work in this area included studies of the structure of [[hemoglobin]] with his student [[Charles D. Coryell]]. He demonstrated that the hemoglobin molecule changes structure when it gains or loses an [[oxygen]] molecule.<ref name=Califano/> As a result of this observation, he decided to conduct a more thorough study of [[protein structure]] in general. He returned to his earlier use of X-ray diffraction analysis. But protein structures were far less amenable to this technique than the crystalline minerals of his former work. The best X-ray pictures of proteins in the 1930s had been made by the British crystallographer [[William Astbury]], but when Pauling tried, in 1937, to account for Astbury's observations quantum mechanically, he could not.<ref name="Livio">{{Cite book |last=Livio |first=Mario |url=https://books.google.com/books?id=0XmmAwAAQBAJ&pg=PA285 |title=Brilliant blunders: from Darwin to Einstein: colossal mistakes by great scientists that changed our understanding of life and the universe |date=2014 |publisher=Simon & Schuster |isbn=978-1-4391-9237-5 |location=[S.l.]}}</ref>

It took eleven years for Pauling to explain the problem: his [[mathematics|mathematical]] analysis was correct, but Astbury's pictures were taken in such a way that the protein molecules were tilted from their expected positions. Pauling had formulated a model for the structure of hemoglobin in which atoms were arranged in a [[helix|helical]] pattern, and applied this idea to proteins in general.{{citation needed|date=August 2023}}

In 1951, based on the structures of [[amino acid]]s and [[peptide]]s and the planar nature of the [[peptide bond]], Pauling, [[Robert Corey]] and [[Herman Branson]] correctly proposed the [[alpha helix]] and [[beta sheet]] as the primary [[structural motif]]s in protein [[secondary structure]].<ref>{{Cite journal |last1=Pauling |first1=L |last2=Corey |first2=RB |year=1951 |title=Configurations of Polypeptide Chains With Favored Orientations Around Single Bonds: Two New Pleated Sheets |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=37 |issue=11 |pages=729–40 |bibcode=1951PNAS...37..729P |doi=10.1073/pnas.37.11.729 |pmc=1063460 |pmid=16578412 |doi-access=free}}</ref><ref name="Goertzel and Goertzel, p. 95-100">Goertzel and Goertzel, p. 95-100.</ref> This work exemplified Pauling's ability to think unconventionally; central to the structure was the unorthodox assumption that one turn of the helix may well contain a non-[[integer]] number of amino acid residues; for the alpha helix it is 3.7 amino acid residues per turn.{{citation needed|date=August 2023}}

Pauling then proposed that [[deoxyribonucleic acid]] (DNA) was a [[triple helix]];<ref>{{Cite journal |last1=Pauling |first1=L |last2=Corey |first2=RB |date=February 1953 |title=A Proposed Structure For The Nucleic Acids |journal=Proc Natl Acad Sci U S A |volume=39 |issue=2 |pages=84–97 |bibcode=1953PNAS...39...84P |doi=10.1073/pnas.39.2.84 |pmc=1063734 |pmid=16578429 |doi-access=free}}</ref><ref>{{Cite web |title=Linus Pauling's DNA Model |url=http://www.farooqhussain.org/projects/paulingdnamodel |url-status=dead |archive-url=https://web.archive.org/web/20120204210701/http://www.farooqhussain.org/projects/paulingdnamodel |archive-date=February 4, 2012 |access-date=June 2, 2015}}</ref> his model contained several basic mistakes, including a proposal of neutral phosphate groups, an idea that conflicted with the acidity of DNA. [[William Lawrence Bragg|Sir Lawrence Bragg]] had been disappointed that Pauling had won the race to find the alpha [[Alpha helix|helix structure]] of proteins. Bragg's team had made a fundamental error in making their models of protein by not recognizing the planar nature of the peptide bond. When it was learned at the [[Cavendish Laboratory]] that Pauling was working on molecular models of the structure of DNA, [[James Watson]] and [[Francis Crick]] were allowed to make a molecular model of DNA. They later benefited from unpublished data from [[Maurice Wilkins]] and [[Rosalind Franklin]] at [[King's College London|King's College]] which showed evidence for a helix and planar base stacking along the helix axis. Early in 1953 Watson and Crick proposed a correct structure for the DNA double helix. Pauling later cited several reasons to explain how he had been misled about the structure of DNA, among them misleading density data and the lack of high quality X-ray diffraction photographs. Pauling described this situation as "the biggest disappointment in his life".<ref name="Dye-LATimes">{{Cite web |last=Dye |first=Lee |date=June 2, 1985 |title=The Deeply Personal War of Linus Pauling: Nobel Prize-Winning Chemist Still Battles for His Controversial Vitamin Theory |url=https://www.latimes.com/archives/la-xpm-1985-06-02-vw-15174-story.html |access-date=April 9, 2023 |website=[[Los Angeles Times]] |language=en-US}}</ref>

During the time Pauling was researching the problem, Rosalind Franklin in England was creating the world's best images. They were key to Watson's and Crick's success. Pauling did not see them before devising his mistaken DNA structure, although his assistant Robert Corey did see at least some of them, while taking Pauling's place at a summer 1952 protein conference in England. Pauling had been prevented from attending because his passport was withheld by the State Department on suspicion that he had Communist sympathies. This led to the legend that Pauling missed the structure of DNA because of the politics of the day (this was at the start of the [[McCarthyism|McCarthy]] period in the United States). Politics did not play a critical role. Not only did Corey see the images at the time, but Pauling himself regained his passport within a few weeks and toured English laboratories well before writing his DNA paper. He had ample opportunity to visit Franklin's lab and see her work, but chose not to.<ref name="Nature" />{{rp|414–415}} Despite these times, Pauling chose to move on from them and be thankful for the discoveries that he had already found.<ref name="Dye-LATimes"/>

Pauling also studied [[enzyme]] reactions and was among the first to point out that enzymes bring about reactions by stabilizing the [[transition state]] of the reaction, a view which is central to understanding their mechanism of action.<ref>{{Cite book |last=Metzler |first=David E. |url=https://books.google.com/books?id=X194AYXInC8C&pg=PA330 |title=Biochemistry |date=2003 |publisher=Harcourt, Academic Pr. |isbn=978-0-12-492541-0 |edition=2nd |location=San Diego |ref=Metzler}}</ref> He was also among the first scientists to postulate that the binding of [[antibodies]] to antigens would be due to a complementarity between their structures.<ref name="Lewis">{{Cite book |first1=Julius M. |last1=Cruse |first2=Robert E. |last2=Lewis  |url=https://books.google.com/books?id=kNI5Lk2z37sC&pg=PA21 |title=Atlas of immunology |date=2010 |publisher=CRC Press/Taylor & Francis |isbn=978-1-4398-0268-7 |edition=3rd |location=Boca Raton, FL |page=21 |access-date=May 27, 2015}}</ref> Along the same lines, with the physicist turned biologist [[Max Delbrück]], he wrote an early paper arguing that [[DNA replication]] was likely to be due to [[Complementarity (molecular biology)|complementarity]], rather than similarity, as suggested by a few researchers. This was made clear in the model of the structure of DNA that Watson and Crick discovered.<ref name="Tudge">{{Cite book |last=Tudge |author-link=Colin Tudge |first=Colin |url=https://books.google.com/books?id=Wprqex2OGY4C&pg=PT74 |title=The engineer in the garden: Genes and genetics: from the idea of heredity to the creation of life |date=1995 |publisher=Hill and Wang |isbn=978-0-8090-4259-3 |edition=1st American |location=New York |access-date=May 27, 2015}}</ref>

===Molecular genetics===
[[File:Linus Pauling 1948.png|thumb|Pauling in 1948]]

In November 1949, Pauling, [[Harvey Itano]], [[Seymour Jonathan Singer|S. J. Singer]] and Ibert Wells published "[[Sickle Cell Anemia, a Molecular Disease]]"<ref name="Itano">{{Cite journal |last1=Pauling |first1=L. |last2=Itano |first2=H. A. |last3=Singer |first3=S. J. |author3-link=Seymour Jonathan Singer |last4=Wells |first4=I. C. |date=November 25, 1949 |title=Sickle Cell Anemia, a Molecular Disease |url=http://scarc.library.oregonstate.edu/coll/pauling/blood/papers/1949p.15.htmlfddsf |journal=Science |volume=110 |issue=2865 |pages=543–548 |bibcode=1949Sci...110..543P |doi=10.1126/science.110.2865.543 |pmid=15395398 |s2cid=31674765 |access-date=June 2, 2015 }}{{Dead link|date=May 2025 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> in the journal ''Science''. It was the first proof of a human disease being caused by an abnormal protein, and [[sickle cell anemia]] became the first disease understood at the molecular level. (It was not, however, the first demonstration that variant forms of hemoglobin could be distinguished by electrophoresis, which had been shown several years earlier by [[Maud Menten]] and collaborators).<ref>{{Cite journal |last1=Andersch |first1=MA |last2=Wilson |first2=DA |last3=Menten |first3=ML. |year=1944 |title=Sedimentation constants and electrophoretic mobilities of adult and fetal carbonylhemoglobin |journal=Journal of Biological Chemistry |volume=153 |pages=301–305 |doi=10.1016/S0021-9258(18)51237-0 |doi-access=free}}</ref> Using [[electrophoresis]], they demonstrated that individuals with [[sickle cell disease]] have a modified form of hemoglobin in their [[red blood cell]]s, and that individuals with [[sickle cell trait]] have both the normal and abnormal forms of hemoglobin. This was the first demonstration causally linking an abnormal protein to a disease, and also the first demonstration that [[Mendelian inheritance]] determines the specific physical properties of proteins, not simply their presence or absence – the dawn of [[molecular genetics]].<ref name="Strasser">{{Cite journal |last=Strasser |first=Bruno J. |date=August 30, 2002 |title=Linus Pauling's "molecular diseases": Between history and memory |url=http://biologie.unige.ch/assets/brunostrasser/Strasser_AJMG_2002.pdf |archive-url=https://ghostarchive.org/archive/20221009/http://biologie.unige.ch/assets/brunostrasser/Strasser_AJMG_2002.pdf |archive-date=October 9, 2022 |url-status=live |journal=American Journal of Medical Genetics |volume=115 |issue=2 |pages=83–93 |citeseerx=10.1.1.613.5672 |doi=10.1002/ajmg.10542 |pmid=12400054 |access-date=May 27, 2015}}</ref>

His success with sickle cell anemia led Pauling to speculate that a number of other diseases, including mental illnesses such as [[schizophrenia]], might result from flawed genetics. As chairman of the Division of Chemistry and Chemical Engineering and director of the Gates and Crellin Chemical Laboratories, he encouraged the hiring of researchers with a chemical-biomedical approach to mental illness, a direction not always popular with established [[California Institute of Technology|Caltech]] chemists.<ref name="LATimes1994">{{Cite news |date=August 21, 1994 |title=A Flamboyant Scientist's Legacy : Scholar: Linus C. Pauling's supporters and detractors join in calling the two-time Nobel winner one of the most significant figures of this century |work=Los Angeles Times |url=https://www.latimes.com/archives/la-xpm-1994-08-21-mn-29601-story.html |access-date=June 1, 2015}}</ref>{{rp|2}}

In 1951, Pauling gave a lecture entitled "Molecular Medicine".<ref>{{Cite web |last=Pauling |first=Linus |date=October 1951 |title=Molecular Medicine |url=http://scarc.library.oregonstate.edu/coll/pauling/blood/pictures/1951s.17.html |access-date=August 5, 2007 |publisher=Ava Helen and Linus Pauling Papers}}</ref> In the late 1950s, he studied the role of enzymes in brain function, believing that mental illness may be partly caused by enzyme dysfunction.  In the 1960s, as part of his interest in the effects of nuclear weapons, he investigated the role of mutations in evolution, proposing with his student Emile Zuckerkandl, the molecular evolutionary clock, the idea that mutations in proteins and DNA accumulate at a constant rate over time .<ref name="Morgan">{{Cite journal |last=Morgan |first=Gregory J. |date=1998 |title=Emile Zuckerkandl, Linus Pauling, and the molecular evolutionary clock, 1959–1965 |url=https://www.jstor.org/stable/4331476|journal=Journal of the History of Biology |volume=31 |issue=2 |pages=155–78| doi=10.1023/A:1004394418084|jstor=4331476 |pmid=11620303 |s2cid=5660841 |access-date=June 11, 2023|url-access=subscription }}</ref>

===Structure of the atomic nucleus===
[[File:Linus Pauling 1962.jpg|thumb|Pauling in 1962]]

On September 16, 1952, Pauling opened a new research notebook with the words "I have decided to attack the problem of the structure of nuclei." On October 15, 1965, Pauling published his Close-Packed Spheron Model of the atomic nucleus in two well respected journals, ''Science'' and the ''[[Proceedings of the National Academy of Sciences]]''.<ref name="SpheronPNAS">{{Cite journal |last=Pauling |first=Linus |date=1965 |title=The Close-Packed Spheron Model of atomic nuclei and its relation to the shell model |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=54 |issue=4 |pages=989–994 |bibcode=1965PNAS...54..989P |doi=10.1073/pnas.54.4.989 |pmc=219778 |pmid=16578621 |doi-access=free}}</ref><ref name="SpheronScience">{{Cite journal |last=Pauling |first=L |date=October 15, 1965 |title=The close-packed-spheron theory and nuclear fission |url=http://scarc.library.oregonstate.edu/coll/pauling/rnb/26/26-026.html |journal=Science |volume=150 |issue=3694 |pages=297–305 |bibcode=1965Sci...150..297P |doi=10.1126/science.150.3694.297 |pmid=17742357|url-access=subscription }}</ref> For nearly three decades, until his death in 1994, Pauling published numerous papers on his spheron cluster model.<ref name=SpheronPNAS/><ref>{{Cite web |last=Pauling |first=Linus |date=July 1966 |title=The close-packed-spheron theory of nuclear structure and the neutron excess for stable nuclei (Dedicated to the seventieth anniversary of Professor Horia Hulubei) |url=http://scarc.library.oregonstate.edu/coll/pauling/rnb/26/26-048.html |access-date=August 5, 2007 |publisher=Revue Roumain de Physique}}</ref><ref>{{Cite journal |last=Pauling |first=Linus |date=December 1967 |title=Magnetic-moment evidence for the polyspheron structure of the lighter atomic nuclei |url=http://scarc.library.oregonstate.edu/coll/pauling/rnb/26/26-068.html |journal=Proceedings of the National Academy of Sciences |volume=58 |issue=6 |pages=2175–2178 |bibcode=1967PNAS...58.2175P |doi=10.1073/pnas.58.6.2175 |pmc=223816 |pmid=16591577 |access-date=August 5, 2007 |doi-access=free}}</ref><ref>{{Cite journal |last=Pauling |first=Linus |date=November 1969 |title=Orbiting clusters in atomic nuclei |url=http://scarc.library.oregonstate.edu/coll/pauling/rnb/26/26-075.html |journal=Proceedings of the National Academy of Sciences of the United States of America |publisher=Proceedings of the National Academy of Sciences |volume=64 |issue=3 |pages=807–9 |bibcode=1969PNAS...64..807P |doi=10.1073/pnas.64.3.807 |pmc=223305 |pmid=16591799 |access-date=August 5, 2007 |doi-access=free}}</ref><ref>{{Cite web |last1=Pauling |first1=Linus |last2=Arthur B. Robinson |year=1975 |title=Rotating clusters in nuclei |url=http://scarc.library.oregonstate.edu/coll/pauling/rnb/26/26-084.html |access-date=August 5, 2007 |publisher=Canadian Journal of Physics}}</ref><ref>{{Cite journal |last=Pauling |first=Linus |date=February 1991 |title=Transition from one revolving cluster to two revolving clusters in the ground-state rotational bands of nuclei in the lanthanon region |url=http://scarc.library.oregonstate.edu/coll/pauling/rnb/26/26-125.html |journal=[[Proceedings of the National Academy of Sciences|Proc. Natl. Acad. Sci.]] |volume=88 |issue=3 |pages=820–823 |bibcode=1991PNAS...88..820P |doi=10.1073/pnas.88.3.820 |pmc=50905 |pmid=11607150 |access-date=August 5, 2007 |doi-access=free}}</ref>

The basic idea behind Pauling's spheron model is that a nucleus can be viewed as a set of "clusters of nucleons". The basic nucleon clusters include the [[deuteron]] [np], [[helion (chemistry)|helion]] [pnp], and [[tritium|triton]] [npn]. [[Even-even nucleus|Even–even nuclei]] are described as being composed of clusters of [[alpha particle]]s, as has often been done for light nuclei.<ref name="Clusters">{{Cite journal |last=Pauling |first=Linus |date=November 15, 1969 |title=Orbiting clusters in atomic nuclei |journal=Proceedings of the National Academy of Sciences |volume=64 |issue=3 |pages=807–809 |bibcode=1969PNAS...64..807P |doi=10.1073/pnas.64.3.807 |pmc=223305 |pmid=16591799 |doi-access=free}}</ref> Pauling attempted to derive the shell structure of nuclei from pure geometrical considerations related to [[Platonic solids]] rather than starting from an independent particle model as in the usual [[Nuclear shell model|shell model]]. In an interview given in 1990 Pauling commented on his model:<ref name="AOA">{{Cite web |title=Linus C. Pauling, Ph.D. Biography and Interview |url=https://www.achievement.org/achiever/linus-pauling/#interview/ |website=www.achievement.org |publisher=[[American Academy of Achievement]]}}</ref>

{{blockquote|Now recently, I have been trying to determine detailed structures of atomic nuclei by analyzing the ground state and excited state vibrational bends, as observed experimentally. From reading the physics literature, Physical Review Letters and other journals, I know that many physicists are interested in atomic nuclei, but none of them, so far as I have been able to discover, has been attacking the problem in the same way that I attack it. So I just move along at my own speed, making calculations ...}}