Quentin H. Gibson, who is best known for his pioneering work on the kinetics of ligand binding to hemoglobins and the development of stopped-flow and flash photolysis instruments, passed away on March 16, 2011 in Hanover, N.H., at the age of 92.
Gibson was born on Dec. 9, 1918 in Aberdeen, Scotland. In 1926, his father was appointed director of the Linen Industry Research Association, and the family moved to Glenmore House, Lambeg, Northern Ireland, about 10 miles south of Belfast, where Quentin spent his youth among the research laboratories and the elaborate grounds. He enrolled in Queen’s University Belfast, receiving an M.D. in 1944 and a Ph.D. in 1946. Gibson’s graduate research was based on studies of the reaction of methemoglobin with ascorbate, which reverses methemoglobinanemia (1, 2). His work with D.C. Harrison on familial idiopathic methemoglobinanemia was the first to show a genetic disorder to be due to an enzyme defect. In the Belfast cases, the anemia was due to the loss of diaphorase I activity, which now is known as NADH methemoglobin reductase or cytochrome-b5 reductase.
From 1947 to 1956, Gibson was successively appointed a lecturer, senior lecturer, and reader in the department of physiology in the school of medicine at the University of Sheffield. During this time, he began close collaborations with F. J. W. Roughton, who in 1923 built the first rapid mixing device with H. Hartridge to examine the rates of O2 and CO binding to hemoglobin and red cells. Gibson, who was a skilled machinist, designed and built a stopped-flow, rapid mixing spectrometer (3) and a flash photolysis apparatus (4, 5) to re-examine these reactions and, with Roughton, showed for the first time that the major increase in iron reactivity during cooperative ligand binding does not occur until roughly three ligands have been bound. Gibson and his colleagues then used these instruments to examine a variety of enzymatic and globin reactions. The stopped-flow spectrometer was commercialized by Durrum (later Dionex) Instruments, Inc. and sold as the “Durrum-Gibson” instrument until approximately 1990.
While at the University of Sheffield, Gibson married and started a family. His wife, Audrey Jane (Pinsent) Gibson, obtained a doctorate from the University of London in 1949, where she discovered that selenite is required for the production of formate dehydrogenase in coliforms. After a year of study with C.B. Van Niel in California, she took a position in Sidney Elsden laboratory in Sheffield to characterize c-type cytochromes from photosynthetic bacteria. Like her husband, she had a long and distinguished career before her death on June 10, 2008.
In 1957, Gibson was awarded a professorship and the chair of the department of biochemistry at the University of Sheffield, replacing Hans Krebs, who took a position at the University of Oxford. Gibson brought together a remarkable group of biophysicists and enzymologists, including Gregorio Weber, Vincent Massey and Keith Dalziel, who each were elected either fellows of the London Royal Society or members of the U.S. National Academy of Sciences.
In 1963, Gibson moved to the United States to take a joint professorship of biophysics and physical biochemistry at the Johnson Research Foundation and of physiology in the graduate school of medicine at the University of Pennsylvania. While in Philadelphia, Gibson expanded his own work to studies of a variety of enzymes and, with Colin Greenwood, made the first measurements of bimolecular O2 binding to cytochrome c oxidase using a newly constructed flow flash apparatus, which set the standard for these types of measurements for more than 30 years.
In 1965, Gibson became the Greater Philadelphia Professor in the Section of Biochemistry, Molecular and Cell Biology at Cornell University, where he remained until his retirement in 1996. While at Cornell, Gibson was elected a fellow of the London Royal Society in 1969, became a member of the U.S. National Academy of Sciences immediately after becoming a U.S. citizen in 1982, served as an associate editor of the Journal of Biological Chemistry from 1975 to 1994, and received the Keilin Memorial Medalist Award and Lectureship in 1990.
During his early years at Cornell, Gibson and Richard DeSa automated the collection of data from all his rapid kinetic instruments, using minicomputers to provide the first millisecond digital readouts of kinetic data in enzymology. This technology was applied to a complete analysis of O2 binding. Both equilibrium curve and time course data were analyzed by combined analog and digital computing. Next, Gibson turned his attention to the problems associated with naturally occurring hemoglobinopathies, the properties of globins from a variety of plant and animal species, the differences between the alpha and beta subunits of human hemoglobin, and the rate of the R to T quaternary transition.
After developing a stomach ulcer in 1969, Gibson decided to spend his summers at Woods Hole, which he did from 1970 to approximately 1990. He and his wife Jane bought a house there and a sailboat, which he used every summer until Hurricane Gloria destroyed it in 1985. Jane taught in the summer microbiology course at the Marine Biological Laboratory, and Quentin went out on expeditions to collect fish blood with Frank Carey. After he returned to Cornell in the fall, his students studied ligand binding to fish Hbs, which showed unusual pH and temperature effects (6).
In the 1980s, Gibson’s group constructed laser photolysis systems to examine internal (geminate) rebinding within the globin molecules at room temperature. These experiments then were used to determine pathways for ligand movement into and out of the protein matrix using site-directed mutagenesis in collaboration with a variety of laboratories. In the 1990s, Ron Elber helped Gibson implement the use of molecular dynamics simulations for interpreting the ultrafast picosecond and nanosecond recombination processes that were being measured in his laboratory with both native and mutant proteins.
In 1996, Gibson and his wife retired from Cornell University and moved permanently to Etna, N.H. They spent the winter months of 1996 to 2001 in Houston, Texas. There, Quentin worked in a kinetics laboratory set up for him at Rice University, continuing his collaborative studies with John Olson and George Phillips, while Jane worked in the microbiology department at the University of Texas Medical School Houston. This time period was highly productive and led to a detailed map of the pathway for O2 migration into and out of Mb. In 2002, Gibson decided to stay year-round in New Hampshire, but a small kinetics laboratory in William Royer’s laboratory at the University of Massachusetts Medical School allowed him to keep doing experiments on hemoglobins until 2009, the year his last research article appeared in print. Even after he was unable to make the trip to Worcester, Gibson continued to advise the Royer lab on both experimental techniques and interpretations of kinetic data well into the last year of his life.
Gibson’s career truly was remarkable. He published papers from 1943 to 2009, a span of almost seven decades. When he began his studies of hemoglobin in the 1940s, its structure was completely unknown, but when he ended his career, his papers described detailed movements of diatomic oxygen through a gate opened by rotation of the distal histidine and then its capture in well-specified cavities in the protein that were engineered by recombinant DNA technology, visualized by time-resolved X-ray crystallography, and analyzed by molecular dynamics simulations. In 2004, he wrote a detailed and amusing history of these changes in our understanding of hemoglobin kinetics (7).
A few months before his death, the regents of the University of Sheffield recognized Gibson’s contributions to science and to the reputation of their institution by granting him an honorary Doctorate of Science and establishing an eponymous lectureship. In January of 2011, he reflected peacefully and with contentment that this honor had brought his academic career full circle.
1. Gibson, Q. H. (1993) Historical note: methemoglobinemia – long ago and far away. Am. J. Hematol. 42, 3 – 6.
2. Gibson, Q. (2002) Introduction: congenital methemoglobinemia revisited. Blood 100, 3445 – 3446.
3. Gibson, Q. H. (1954) Stopped-Flow Apparatus for the Study of Rapid Reactions, Discuss. Faraday Soc. 137 – 139.
4. Gibson, Q. H., and Milnes, L. (1964) Apparatus for rapid and sensitive spectrophotometry. Biochem. J. 91, 161 – 171.
5. Gibson, Q. H. (1956) An apparatus for flash photolysis and its application to the reactions of myoglobin with gases. J. Physiol. 134, 112 – 122.
6. Andersen, M. E., Olson, J. S., Gibson, Q. H., and Carey, F. G. (1973) Studies on ligand binding to hemoglobins from teleosts and elasmobranchs. J. Biol. Chem. 248, 331 – 341.
7. Gibson, Q. H. (2004) Hemoglobin Kinetics – A Retrospect. Comprehensive Biochemistry (G. Semenza and A. J. Turner, Volume Eds.) 43, 101 – 197.
John Olson (firstname.lastname@example.org) is the Ralph and Dorothy Looney professor of biochemistry and cell biology at Rice University. William Royer (William.Royer@umassmed.edu) is a professor of Biochemistry and Molecular Pharmacology at the University of Massachusetts Medical School.
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