Gary K. Ackers

(1939-2011)

Gary K. AckersGary K. Ackers at age 12 had his career figured out. He didn’t just want to be a scientist. He wanted to uncover the most basic rules of life..those that govern biological molecules. He haunted bookstores and got to know biologists at the University of California. His passion for science increased in 1953, when discovery of the structure of DNA showed that chemistry and physics could explain the most fundamental processes of life. He won the San Francisco Bay Area Science Fair Grand Prize at age 14 and was fourth in the national competition with his project that involved scooping bacteria from Calistoga’s scalding springs. He showed that bacteria’s growth rate was a function of temperature and calculated how much energy was needed to start the reaction that limited this rate.

Gary majored in chemistry and mathematics at Harding College in Arkansas. He published his first five scientific papers as an undergraduate from results that he obtained during the summers while working in the U.S. Department of Agriculture’s Plant Virus Laboratory in Beltsville, MD. To determine size, he ran viruses through gels, adapting a technique called size exclusion chromatography.

Gary Ackers earned his doctorate in physiological chemistry with Tom Thompson at Johns Hopkins University. He used size exclusion chromatography to discover how proteins assemble into complexes and how assembly affects function.

He spent ten years at the University of Virginia School of Medicine as Assistant Professor (1966-1967), Associate Professor (1967-1972), Professor (1972-1977). While at the University of Virginia School of Medicine, he was in the Biochemistry Department, Chairman of the Biophysics program, Director of Graduate Admissions and in the Program in Molecular/Cell Biology. During this time Ackers was exploring subunit interactions in several enzymes, he had a flash of inspiration.. He suddenly realized that understanding the strength of association between four subunits of hemoglobin at all levels of bound oxygen would be key to unraveling the mystery of how the protein functions.

In the summer of 1977, Ackers taught a course at Woods Hole Marine Biological Laboratory with scientists from the Johns Hopkins main campus. This led to a position in the Department of Biology and the McCollum-Pratt Institute at Johns Hopkins. He also studied protein-DNA interactions in collaboration with a group at Harvard. Dr. Ackers also served as Professor of Biophysics and Director of the Institute for Biophysical Research on Macromolecular Assemblies, which he founded through the National Science Foundation in the late 1980s. This is a university-wide training program in molecular biophysics that has continued for decades.

While at Johns Hopkins, he also played a leading role in the establishment of the Gibbs Conference on Biothermodynamics, an annual meeting organized to promote innovative development of biophysical principles applied to current problems in biology and to train the next generation of molecular biophysicists to tackle hard problems rigorously. The Gibbs Conference on Biothermodynamics honored him in 2009 with the inaugural Gary K. Ackers Lecture in Biothermodynamics. Gary was an active member of the Biophysical Society throughout his career and served as President of the Society in 1984. He was the 1994 recipient of the Founder’s Award. This award honors a scientist for outstanding achievement in biophysics. These achievements will be reflected in the acceptance and use of these ideas in the awardees field..either promptly or over a period of years. In 2000, he was awarded Fellow of the Biophysical Society. This award honors distinguished members that have demonstrated a long period of scientific excellence.

Dr. Ackers relocated to Washington University School of Medicine in St. Louis, MO, in 1989 as the Raymond H. Wittcoff Professor and Head of the Biochemistry department. He served as the Head of the department until 1996 when Ackers decided to step down so that he would have more time for research and teaching. While Head of the department, he established a world renowned group of biophysics oriented faculty, a Molecular Biophysics program focusing on quantitative measurements of biological processes and computational modeling of complex behaviors and expanded the new Department of Biochemistry and Molecular Biophysics. He became professor emeritus in 2007.

Gary was a pioneer in the development of methods and application of principles of equilibrium thermodynamics to the study of linkage in complex macromolecular assemblies. Studies from his laboratory on the energetics of self-association and ligand binding in human hemoglobin proved unequivocally that the classic and elegant MWC model of intersubunit allostery was insufficient to explain cooperative oxygen binding: the position, as well as the number, of ligands matters. His contributions in this area greatly enhanced our understanding of the relationship between structure, energy and function in hemoglobin, and in multimeric allosteric systems in general. By probing ever more deeply into the molecular mechanism of cooperativity, he demonstrated a beautiful, useful, and general strategy for dissecting functional energetics in macromolecular assemblies.

His quantitative study of the interactions between proteins and nucleic acids in the bacteriophage lambda system included the development of quantitative DNase footprinting methods for measuring free energies of repressor-operator interactions. The footprinting assay remains an effective tool for measuring the extremely tight binding constants that are often encountered in site-specific interactions between proteins and nucleic acids. Those studies paved the way for similar methods to study protein-nucleic acid interactions in more complex systems, including time-resolved studies of the kinetics of RNA folding. Based on his experimental studies of phage lambda, his group developed statistical thermodynamic models to simulate the lysogenic-to-lytic growth switch: the series of macromolecular events that determine the fate of bacteriophage lambda during infection of E. coli. This work demonstrated how a complex biological function could be predicted quantitatively, strictly from the kinetics of transcription and translation, and the Gibbs free energy of interactions between the key macromolecular components in the genetic switch.

During Gary’s early career, he developed methods to measure association constants in self-associating systems based on analytical gel permeation chromatography. Those methods have since become standard tools in the field. His group was also responsible for modifications of the cryo-gel electrophoresis methods, moving from applying them to hemoglobin to protein- DNA interactions. These contributions focused on developing the capacity to quantify intermediate states that are only transiently populated during the course of a biochemical process. His more than 200 articles and chapters changed our view of the molecular mechanisms that govern complex biochemical reactions.

Gary had a sense of humor and propensity for scientific puns. He was known for the rigor of his experimental methods and was deeply gratified by the success of the graduate and postdoctoral students who trained in his laboratory. During the course of his career, he lectured across the United States, Europe, the former Soviet Union and China. Gary’s legacy continues in the work of colleagues who were influenced by one of the great biophysicists of our time.

Remembrances:

“I remember Gary both as a humorous person and a excellent scientist, and
I appreciate the cordial and collaborative atmosphere in Biochemistry
and Molecular Biophysics Department back when I was there.”

John Hsieh, PhD

“This is sad news but also what happened to Gary Ackers at the end of his
life. He was a great scientist and I remember the high level of science
that one experienced in his laboratory. I send to his family, colleagues
and to the department my most sincere condolences.”

Dr. Laurent Kiger

“I just read about the death of Dr. Ackers in the Biophysical Society newsletter. It is such a loss for the scientific society. I have known him since my graduate student days when I was working on hemoglobin in Tom Spiro’s laboratory. I still remember vividly my visit to his lab in 1995 and talking to him in his office which had a 3D structure of hemoglobin, and him joking with me and saying we both shared a common love; “hemoglobin”. Both Gary and Jo have been mentors to me during my research career even though I never really worked in their laboratory. Please pass my condolences to Jo Holt and Gary’s family.”

Vasanthi Jayaraman, Ph.D.

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**Parts of the article were excerpted from “Mastering mysteries of molecular machines” by Linda Sage, published Sept. 2, 1999, in the Washington University Record.

**Parts of the article were excerpted from Dr. Michael D. Brenowitz’ speech at the Inaugural Gary K. Ackers Lecture in Biological Thermodynamics in 2009. Dr. Brenowitz is a professor at Albert Einstein College of Medicine.