Hugh E. Huxley

Hugh Huxley, Society Member since 1984, died suddenly on July 25, in Woods Hole, Massachusetts, ending his 65-year long devotion to understanding how muscles contract, as well as our expectation to see this distinguished, thoughtful, and insightful man at every Biophysical Society meeting. In Huxley’s quest to understand contraction, he made landmark contributions that inspired discoveries about how cells move and divide, how cilia and flagella beat, and how molecules and organelles move inside cells.

Huxley was John Kendrew’s first graduate student in the Cavendish Laboratory MRC unit, founded by Max Perutz and John Kendrew. Francis Crick was the other student. Huxley was supposed to do X-ray analysis of proteins, but became interested in muscle. By assembling an X-ray system from borrowed and built parts in frog leg muscles he was able to see meridional patterns in a hexagonal lattice, now known to be from myosin and actin, that showed a lateral redistribution of material during contraction. Actin and myosin were known to be separate proteins, but contrary to what others had proposed, Huxley concluded that they were in separate filaments. Armed with speculations about the meaning of the diffraction patterns, he went to MIT where he and Jean Hanson did their famous EM experiments on muscle showing that two interdigitating sets of filaments in each sarcomere slide past one another to produce shortening without changing in length themselves. This led to postulation of the sliding filament mechanism of muscle contraction in 1953. Back in London, using an improved microtome to produce ultrathin sections, he saw crossbridges between the thick and thin filaments (1957). By comparing negatively-stained images of thin and thick filaments with synthetic filaments made from extracted proteins, he saw that crossbridges are projections from myosin filaments (1963). In 1969 he proposed the swinging crossbridge model to explain how myosin moves on actin. Changes in the actin layer lines led to postulation of the steric blocking model of Ca2+ regulation in which movement of tropomyosin occurs before tension development (1972).

Today the sliding filament model seems obvious, so ingrained in our thinking that it is hard to realize it remained controversial for years. Refinements driven by novel EM imaging methods, improved X-ray detectors with greater time resolution and ever more intense X-ray sources have given new insights into how myosin crossbridges work on actin; these finally proved the model, even to Huxley’s satisfaction. It is easy to enumerate these advances, but each happened because Huxley was determined to get the best data, by developing new methods and modifying equipment, experimental conditions and techniques. As the details of the mechanism have come into finer focus, his pioneering work has stimulated the motility field in general, howing that molecular motors are at the heart of nature’s machines.

Huxley was born in Cheshire, England. He attended the University of Cambridge, served in the Royal Air Force during World War II as a radar officer, and returned to Cambridge after the war, where he received his PhD. After a postdoc at MIT and a position at University College, London, he returned to Cambridge in 1962 to become a founding member of the MRC-Laboratory of Molecular Biology. In 1987 he joined Brandeis University where he remained until his death. Huxley valued his family and friends, enjoyed traveling, skiing, sailing, and tinkering with machines. He is survived by his wife, Frances, his daughter, Olwen, and stepchildren, Bill, Glenway, and Amy Fripp.

Sarah Hitchcock-DeGregori
Sarah Hitchcock-DeGregori worked with Hugh Huxley at Brandeis in 1971 and then as a postdoc in Cambridge (1973-1976).
Photo credit: Olwen Huxley

John Gergely

John Gergely, MD, PhD, co-founder and former Director of Boston Biomedical Research Institute (BBRI) died on July 26, 2013, at the age of 94. A Society member since 1957 and Fellow since 2003, Gergely was recognized for his fundamental contributions to the understanding of the mechanism of muscle contraction, in particular through his pioneering studies of the structure and function of the troponin complex. Gergely did his medical training in Budapest, Hungary, and received his PhD in Biochemistry at the University of Leeds, England. He came to the United States in 1949 and worked at the NIH, University of Wisconsin, and Mass General Hospital, Harvard Medical School. While in Boston, he and Andre Balazs established BBRI to study basic science relevant to human disease and health. Under his leadership, the Department of Muscle Research at BBRI gained international recognition and for several decades was a leading training site for young biochemists worldwide. BBRI was an integral part of John’s life and he continued to visit it until its recent closing. He will be remembered by numerous students, postdoctoral fellows, and junior colleagues for his wisdom, kindness, and objectiveness toward science and life. Gergely leaves behind, Nora, his wife of 68 years and their eight children and families.

C.L. Albert Wang, Sherwin Lehrer and Zenon Grabarek