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Andrew Huxley
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==Career== Having entered Cambridge in 1935, Huxley graduated with a bachelor's degree in 1938. In 1939, [[Alan Lloyd Hodgkin]] returned from the US to take up a fellowship at Trinity College, and Huxley became one of his postgraduate students. Hodgkin was interested in the transmission of electrical signals along nerve fibres. Beginning in 1935 in Cambridge, he had made preliminary measurements on frog [[sciatic nerve]]s suggesting that the accepted view of the nerve as a simple, elongated battery was flawed. Hodgkin invited Huxley to join him researching the problem. The work was experimentally challenging. One major problem was that the small size of most [[neurons]] made it extremely difficult to study them using the techniques of the time. They overcame this by working at the [[Marine Biological Association]] laboratory in [[Plymouth]] using the [[squid giant axon|giant axon]] of the longfin inshore squid (''[[Doryteuthis pealeii|Doryteuthis (formerly Loligo) pealeii]]''), which have the largest neurons known.<ref>{{cite book |last=Hellier |first=Jennifer L. |title=The Brain, the Nervous System, and Their Diseases |publisher=[[Greenwood Publishing Group|Greenwood]] |year=2015 |isbn=978-1-61069-338-7 |page=532}}</ref> The experiments were still extremely challenging as the nerve impulses only last a few milliseconds, during which time they needed to measure the changing electrical potential at different points along the nerve. Using equipment largely of their own construction and design, including one of the earliest applications of a technique of [[electrophysiology]] known as the [[voltage clamp]], they were able to record ionic currents. In 1939, they jointly published a short paper in ''[[Nature (journal)|Nature]]'' reporting on the work done in Plymouth and announcing their achievement of recording action potentials from inside a nerve fibre.<ref>{{cite journal|last=Hodgkin|first=A. L.|author2=Huxley, A. F.|title=Action potentials recorded from Inside a nerve fibre|journal=Nature|year=1939|volume=144|issue=3651|pages=710–711|doi=10.1038/144710a0|bibcode = 1939Natur.144..710H |s2cid=4104520}}</ref> Then [[World War II]] broke out, and their research was abandoned. Huxley was recruited by the British Anti-Aircraft Command, where he worked on radar control of anti-aircraft guns. Later he was transferred to the Admiralty to do work on naval gunnery, and worked in a team led by [[Patrick Blackett]]. Hodgkin, meanwhile, was working on the development of radar at the Air Ministry. When he had a problem concerning a new type of gun sight, he contacted Huxley for advice. Huxley did a few sketches, borrowed a lathe and produced the necessary parts. Huxley was elected to a research fellowship at Trinity College, Cambridge, in 1941. In 1946, with the war ended, he was able to take this up and to resume his collaboration with Hodgkin on understanding how nerves transmit signals. Continuing their work in Plymouth, they were, within six years, able to solve the problem using equipment they built themselves. The solution was that nerve impulses, or action potentials, do not travel down the core of the fiber, but rather along the outer membrane of the fiber as cascading waves of sodium ions diffusing inward on a rising pulse and potassium ions diffusing out on a falling edge of a pulse. In 1952, they published their theory of how [[action potentials]] are transmitted in a joint paper, in which they also describe one of the earliest computational models in biochemistry.<ref>{{Cite web |last=Le Novère |first=Nicolas |author-link=Nicolas Le Novère |title=hodgkin-huxley squid-axon 1952 |url=https://www.ebi.ac.uk/biomodels/BIOMD0000000020#Overview |access-date=15 December 2023 |website=[[BioModels]]}}</ref> This model forms the basis of most of the models used in neurobiology during the following four decades.<ref>{{cite book |last1=Reilly |first1=J. Patrick |url=https://us.artechhouse.com/Electrostimulation-Theory-Applications-and-Computational-Model-P1468.aspx |title=Electrostimulation: Theory, Applications, and Computational Model |last2=Diamant |first2=Alan M. |date=2011 |publisher=[[Artech House]] |isbn=978-1-60807-108-1 |pages=20–21}}</ref> In 1952, having completed work on action potentials, Huxley was teaching physiology at Cambridge and became interested in another difficult, unsolved problem: how does muscle contract? To make progress on understanding the function of muscle, new ways of observing how the network of filaments behave during contraction were needed. Prior to the war, he had been working on a preliminary design for [[interference microscopy]], which at the time he believed to be original, though it turned out to have been tried 50 years before and abandoned. He, however, was able to make interference microscopy work and to apply it to the problem of muscle contraction with great effect. He was able to view muscle contraction with greater precision than conventional microscopes, and to distinguish types of fiber more easily. By 1953, with the assistance of [[Rolf Niedergerke]], he began to find the features of muscle movement. Around that time, [[Hugh Huxley]] and [[Jean Hanson]] came to a similar observation. Authored in pairs, their papers were simultaneously published in the 22 May 1954 issue of ''Nature''.<ref name=huxley54>{{cite journal|last=Huxley|first=A.F.|author2=Niedergerke, R.|title=Structural changes in muscle during contraction; interference microscopy of living muscle fibres|journal=Nature|year=1954|volume=173|issue=4412|pages=971–3|pmid=13165697|bibcode = 1954Natur.173..971H |doi = 10.1038/173971a0 |s2cid=4275495}}</ref><ref>{{cite journal|last=Huxley|first=H.|author2=Hanson, J.|title=Changes in the cross-striations of muscle during contraction and stretch and their structural interpretation|journal=Nature|year=1954|volume=173|issue=4412|pages=973–76|pmid=13165698|bibcode = 1954Natur.173..973H |doi = 10.1038/173973a0 |s2cid=4180166}}</ref> Thus the four people introduced what is called the [[sliding filament theory]] of muscle contractions.<ref>{{cite journal|last=Huxley|first=A.F|title=A high-power interference microscope|journal=J. Physiol.|year=1954|volume=125|issue=1|pages=11–13|doi=10.1113/jphysiol.1954.sp005186|pmid=13192775|s2cid=222198517|doi-access=free}}</ref> Huxley synthesized his findings, and the work of colleagues, into a detailed description of muscle structure and how muscle contraction occurs and generates force that he published in 1957.<ref>{{cite journal|last=Huxley|first=A.F.|title=Muscle structure and theories of contraction |journal=Prog. Biophys. Biophys. Chem.|year=1957|volume=7|pages=255–318|doi=10.1016/S0096-4174(18)30128-8|pmid=13485191|doi-access=free}}</ref> In 1966 his team provided the proof of the theory, and has remained the basis of modern understanding of muscle physiology.<ref>{{cite journal|last=Gordon|first=AM|author2=Huxley, AF |author3=Julian, FJ |title=The variation in isometric tension with sarcomere length in vertebrate muscle fibres|journal=The Journal of Physiology|year=1966|volume=184|issue=1|pages=170–92|pmid=5921536|pmc=1357553|doi=10.1113/jphysiol.1966.sp007909}}</ref> In 1953, Huxley worked at [[Woods Hole]], [[Massachusetts]], as a Lalor Scholar. He gave the [[Christian Archibald Herter (physician)|Herter Lectures]] at [[Johns Hopkins Medical School]] in 1959 and the Jesup Lectures at [[Columbia University]] in 1964. In 1961 he lectured on [[neurophysiology]] at [[Kiev University]] as part of an exchange scheme between British and Russian professors. He was an editor of the ''[[Journal of Physiology]]'' from 1950 to 1957 and also of the ''[[Journal of Molecular Biology]]''. In 1955, he was elected a [[Fellow of the Royal Society]] and served on the Council of the [[Royal Society]] from 1960 to 1962.<ref>{{cite journal | last1 = Malcolm Simmons | first1 = Robert | year = 2018 | title = Sir Andrew Fielding Huxley OM. 22 November 1917 – 30 May 2012 | journal = [[Biographical Memoirs of Fellows of the Royal Society]] | volume = 65| pages = 179–215| doi = 10.1098/rsbm.2018.0012 | doi-access = free }}</ref> Huxley held college and university posts in Cambridge until 1960, when he became head of the Department of Physiology at [[University College London]]. In addition to his administrative and teaching duties, he continued to work actively on muscle contraction, and also made theoretical contributions to other work in the department, such as that on [[animal reflectors]].<ref>{{cite journal|last=Huxley|first=A.F.|title=A theoretical treatment of reflexion of light by multilayer structures |journal=J. Exp. Biol.|year=1954|volume=48|issue=2|pages=227–245|doi=10.1242/jeb.48.2.227 }}</ref> In 1963, he was jointly awarded the [[Nobel Prize in Physiology or Medicine]] for his part in discoveries concerning the ionic mechanisms of the nerve cell.<ref name=":1" /> In 1969 he was appointed to a Royal Society Research Professorship, which he held in the Department of Physiology at University College London. In 1980, Huxley was elected as President of the Royal Society, a post he held until 1985. In his Presidential Address in 1981, he chose to defend the [[Natural selection theory|Darwinian explanation of evolution]], as his ancestor, T. H. Huxley had in 1860. Whereas T. H. Huxley was defying the bishops of his day, Sir Andrew was countering new theories of periods of accelerated change. In 1983, he defended the Society's decision to elect [[Margaret Thatcher]] as a fellow on the ground of her support for science even after 44 fellows had signed a letter of protest. In 1984, he was elected Master of Trinity, succeeding his longtime collaborator, Sir Alan Hodgkin. His appointment broke the tradition that the office of Master of Trinity alternates between a scientist and an arts man. He was Master until 1990 and was fond of reminding interviewers that Trinity College had more Nobel Prize winners than did the whole of France. He maintained up to his death his position as a fellow at [[Trinity College, Cambridge]], teaching in [[physiology]], [[Natural Sciences (Cambridge)|natural sciences]] and medicine.<ref>[http://www.trin.cam.ac.uk/index.php?pageid=172 The Master of Trinity] at [[Trinity College, Cambridge]]{{Dead link|date=December 2023}}</ref> He was also a fellow of [[Imperial College London]] in 1980.<ref>{{cite web |date=11 September 2023 |title=Nobel Laureates associated with Imperial College London |url=http://www3.imperial.ac.uk/aboutimperial/imperial_people/nobel_laureates |publisher=Imperial College London |access-date=28 December 2011 |archive-date=6 October 2014 |archive-url=https://web.archive.org/web/20141006140047/http://www3.imperial.ac.uk/aboutimperial/imperial_people/nobel_laureates |url-status=dead }}</ref> From his experimental work with Hodgkin, Huxley developed a set of differential equations that provided a mathematical explanation for nerve impulses—the "action potential". This work provided the foundation for all of the current work on voltage-sensitive membrane channels, which are responsible for the functioning of animal nervous systems. Quite separately, he developed the mathematical equations for the operation of myosin "cross-bridges" that generate the sliding forces between actin and myosin filaments, which cause the contraction of skeletal muscles. These equations presented an entirely new paradigm for understanding [[muscle contraction]], which has been extended to provide understanding of almost all of the movements produced by cells above the level of bacteria. Together with the Swiss physiologist Robert Stämpfli, he evidenced the existence of [[saltatory conduction]] in [[myelin]]ated nerve fibres.
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