Hugh Huxley (1924-2013) Biophysicist Who Established the Mechanism of Muscle Contraction

COMMENT OBITUARY Hugh Huxley (1924-2013) Biophysicist who established the mechanism of muscle contraction.

n a career spanning more than 65 years, salt solutions that extract myosin removed how calcium ions regulated cross-bridge Hugh Huxley achieved his lifelong only the optically dense A-bands (another interaction. In 1970, using intense X-ray ambition of understanding how eureka moment). Their 1953 Nature paper, synchrotron radiation, Huxley began time- Imuscles contract. together with earlier X-ray work, provided resolved studies of cross-bridge movement. Huxley, who died on 25 July after a heart the key evidence for the ‘sliding filament’ Huxley’s move in 1988 to Brandeis Univer- attack, was born in 1924 in Cheshire, UK, model of muscle contraction. sity in Waltham, Massachusetts, as director and studied physics at Christ’s College at the of the Rosenstiel Basic Medical Sciences University of Cambridge, UK. His education Research Center, gave him access to even was interrupted by service in the Royal Air more powerful X-ray sources, particularly Force from 1943 to 1947, testing height-to- at Argonne National Laboratory in Illinois. surface (H2S) radar — a ground-scanning Improved detectors with high-sensitivity system used by bomber aircraft. There, charge-coupled devices (used in digital he learned the importance of doing work cameras) enabled him to collect in milli- himself, and experimenting with electrical seconds data that would have taken hours ADDIS/PHOTOFUSION PETE and mechanical devices became a lifetime when he started out. With the atomic struc- passion. Huxley was able to fix a wildly tures of actin and the myosin cross-bridge, inaccurate version of H2S developed for east along with other evidence, he wrote in the Asia by switching from a voltage-controlled European Journal of Biochemistry in 2004 that display system, in which overheating was a he finally had direct evidence for the type of problem, to a current-controlled system. He cross-bridge movement that he had postu- described the feat to me some 60 years later as lated nearly 50 years earlier. It gave him great his first ‘eureka moment’ — for which he was satisfaction that the mechanism by which made a Member of the Order of the British myosin functions in muscle is replicated in Empire (MBE) in 1948. almost all biological movement. His love for With the confidence of youth, that same experimentation had delivered beyond his year, Huxley chose to study muscle structure wildest dreams. using X-ray methods for his PhD. He joined Hugh admired independence of spirit and Max Perutz’s group at the Medical Research enterprise, and he led by example. His pers Council (MRC) Unit for Research on the onality reflected his strong humanist views. Molecular Structure of Biological Systems in Muscle experts were sceptical, but a chance Outside science, he enjoyed travelling, sailing Cambridge, with John Kendrew as his super- meeting with fellow Brit Andrew F. Huxley and skiing; he shared with his wife Frances a visor. As with radar, X-ray crystallography (no relation) at Woods Hole in Massachusetts passion for theatre, relished a fine burgundy was in its infancy, and this project would test lent Hugh’s theory strong support. Andrew and loved the operas of Giacamo Puccini. Huxley’s talent for experimentation, attention Huxley had come to similar conclusions For the LMB’s 50th anniversary in 2012, to detail and determination to succeed. using interference microscopy to analyse and with a new and greatly enlarged LMB Little was known then about the detailed single muscle fibres, although without the opened in 2013, Hugh asked more than 40 structure of muscle. A pattern of dark and fine detail revealed by electron microscopy. academics who had visited the lab between light bands had been identified with light The two Huxleys agreed to publish simulta- 1957 and 1988 to write about how it had microscopy, and the proteins actin and neously, and the papers appeared in Nature influenced their careers. These compiled myosin were known to form filaments that in May 1954, with Hugh Huxley’s the more writings, Memories and Consequences (MRC, interacted, although their exact location in substantial, in my view. This was the defining 2013), provide fascinating reflections. The cell muscle cells was unclear. From the analysis moment in the study of muscle. biologist Richard McIntosh described the of X-ray patterns, Huxley identified big What made the filaments slide? In 1958, atmosphere at the LMB as exuding “quality changes in the intensities of some reflections Huxley discovered myosin ‘cross-bridges’. of thought, care in execution and energy in when muscles were contracted (when ATP, These attach to actin in a herringbone pursuit of excellence, reflecting the power of which provides cells with energy, is removed). fashion in the absence of ATP, and detach intelligent collaboration between labs with He deduced the presence of a hexagonal when ATP is present. They drive muscle different kinds of expertise”. There could be array of two different types of filaments, and motion like rowing oars. no more fitting epitaph for Hugh Huxley. ■ concluded that muscle contraction involved In 1962, Huxley returned to Britain to physical links between myosin and actin. join the newly opened MRC Laboratory of Alan Weeds was hired by Hugh Huxley in Needing visual evidence, he went to the Molecular Biology in Cambridge (LMB), 1967 to establish a biochemistry group to Massachusetts Institute of Technology in where he later became deputy director. Over study myosin, and worked on motile systems Cambridge in late 1952. He was joined by the next 50 years he was relentless in his quest at the Laboratory of Molecular Biology in the biophysicist Jean Hanson and, using to understand cross-bridge movement. His Cambridge, UK, for more than 40 years. He both electron and light microscopy, they seminal 1969 Science paper described the retired in 2005 and is a life fellow of Trinity demonstrated the presence of two sets of swinging cross-bridge model, and subse- College, University of Cambridge, UK. overlapping filaments and found that the quent computer reconstructions showed e-mail: [email protected]