January 2001
Volume 42, Issue 1
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Lecture  |   January 2001
Introducing Paul Hargrave, the 2000 Recipient of the Friedenwald Award
Investigative Ophthalmology & Visual Science January 2001, Vol.42, 1-2. doi:
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      David S. Papermaster; Introducing Paul Hargrave, the 2000 Recipient of the Friedenwald Award. Invest. Ophthalmol. Vis. Sci. 2001;42(1):1-2.

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      © ARVO (1962-2015); The Authors (2016-present)

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It is customary in these introductions to speak of the work of the award recipient and I shall attend to that shortly. But first I want to speak of Paul’s personal history and his character because that profoundly colors the kind of work he does, the kind of teacher he strives to be and the high level of insight and breadth he brings to his work. In all of this, he is truly a “Marathon Man.” 
Paul was born in Palmyra, New York, and demonstrated an early interest in science. For example, after attending a summer science program at Bar Harbor, he brought some mice home (rules were simpler then) to continue studies in his garage on folate and teratology. He ultimately graduated from Colgate University, magna cum laude with honors in Chemistry and Phi Beta Kappa. After a year of graduate school, the lust for travel and teaching expressed itself and he left for East Africa in the AID program (Agency for International Development), a precursor to the Peace Corps. There, he obtained certification as a teacher and taught chemistry, physics and math at the Friend’s School in Kenya. After two years, he toured the Middle East and Europe and then returned to resume graduate work in biochemistry, joining Dr. Finn Wold’s laboratory, at Illinois. There, he met his lovely and talented wife Doris, and they moved to Minneapolis as the lab moved to the University of Minnesota. During this time, he became an accomplished protein chemist. He was able to utilize these skills to great advantage in his Postdoctoral Position with Dr. William J. Dreyer at Caltech where I had also began my career in Vision Research the year before. With a laboratory focus on photoreceptor membranes, Paul took over the study of rhodopsin’s amino acid sequence. 
Now a bit about his character. He goes the distance - he finishes the race. I do not use the title Marathon Man only as a metaphor. He has run 38 marathons, his last just before this meeting in London. He’s run the Boston Marathon three times and has a personal goal of completing a marathon in every state (he’s currently completed 28 with 22 to go). He’s been a nurturing father and husband. Paul and Doris’ daughter, Elizabeth, now 28, completed her graduate work at UT Austin and now has joined Sen. Daschle’s office staff in Washington, D. C. Their son, David, is currently a college student performing in the family tradition with excellent studies. When Doris turned 40, she decided to resume her education. She attended Law School in Gainesville and Paul kicked her out of the house to go to the library while he did the shopping, cooking and much of the parenting. She now has a successful practice in family law there. 
Paul speaks quietly, and moves carefully. There is little of the showman in his personality. But if you listen, you hear a marathon man at work. No stone is left unturned. The scientific papers are never published hurriedly. They are always complete, correct, and make a huge impact in our field. He is generous and comprehensive in his acknowledgment of the work of others. He has an extraordinary record of accomplishment as an educator of teachers and scientists. 
In his research, Paul, Dr. S-L Fong and his close and long-time colleague, Dr. J. Hugh McDowell, worked together in the earliest years, first at Southern Illinois University Medical School in Carbondale, and then at the University of Florida at Gainesville. Throughout the 1970’s and early 80’s, their effort was to comprehensively isolate, sequence and order all the peptides of rhodopsin into the form we all understand today. To those of you who were not yet born in 1970, perhaps I should remind you of how formidable a task this was then. We didn’t have molecular biology, no cDNA’s, blots or mass spectrometers. The amino acid analyzers were sensitive only to the millimolar range. Automated sequencers worked well on abundant water-soluble peptides, but the purification of water-insoluble peptides, of which there are many in rhodopsin, was an enormous problem. Many of his papers on the way to completing rhodopsin’s sequence shared their discoveries about how to manage these peptides arising from the intractable intramembranous domains of rhodopsin. With time though, as the structure of rhodopsin became clear, the field became more rational. Now studies could be explicitly designed to determine which domains became phosphorylated by rhodopsin kinase and which loops bound transducin. His wanderlust, never leaving him, brought him to Poland where he met and entranced Kris Palczewski and Gryzyna Adamus. He brought them to his lab for a most successful postdoctoral experience and launched them on their own distinguished careers. Making monoclonal antibodies to map the surfaces of rhodopsin and its modifications by phosphorylation, they also launched the analysis of rhodopsin’s partners, rhodopsin kinase, transducin, arrestin and protein phosphatase 2A, thereby helping in the international effort to clarify both signal amplification and dark adaptation of rhodopsin. 
Suddenly, in the late 80’s with the arrival of molecular biological techniques, work on rhodopsin greatly expanded. Numerous membrane proteins interacting with trimeric G-proteins were isolated and found to be structurally related to rhodopsin. The decades of work on rhodopsin’s primary structure and the details of the visual cycle became the model for the action of the adrenergic receptors, and then dopamine, cannabinoid, substance P, and literally hundreds of other receptors, even the mating type receptors of chlamydomonas. It became obvious that rhodopsin belonged to a huge and ancient family adapted freely by evolution to conduct the business of sensing the physical and chemical environment and transducing the information usefully to the cell and the organism. Paul’s group conducted comparative studies of sequences of widely divergent rhodopsins, including Florida alligators and ants! He, of course, went out on the hunt. You can well imagine the satisfaction that swept over his friends when the discovery that rhodopsin mutations initiate autosomal dominant retinitis pigmentosa was announced at ARVO in 1989 by Drs. Ted Dryja and Eliot Berson and their colleagues. Paul’s model was up on the screen and the P23H mutation was identified. Now over 70 different mutations and polymorphisms have been identified in human rhodopsin and the clinical-molecular correlation is still a lively subject for clinicians and scientists. So his work was brought to the ophthalmology clinic. 
In addition to all this outstanding laboratory effort, Paul has served the vision community as a Biochemistry Section chairman of ARVO, a member and Chair of the VisA2 Visual Disorders Study Section and as an organizer of FASEB conferences and numerous international symposia. He has edited several volumes of papers on vision. A loyal faculty member, he has not shirked academic responsibility, taking his turn chairing his department at SIU, serving on search committees and Directing the Core Facility for Vision Research at Gainesville. His loyalty and accomplishments have not gone unnoticed. He came to Gainesville as a Jules and Doris Stein Research to Prevent Blindness Professor and in 1990 was named the Francis N. Bullard Professor and Eminent Scholar of Ophthalmology and Biochemistry. They also conferred numerous awards for his achievements in research, the latest, the University of Florida Superior Accomplishment Award this year. He has been continuously supported by NIH awards since first establishing his independent laboratory at SIU. 
Now, Paul is back in airplanes and pounding the roads again–for both personal and scientific reasons. He’s off to Cambridge, England to work with the Shertler group to determine the three-dimensional shape of rhodopsin. Like all fine marathon runners, steep slopes are seen simply as nature’s way to test you and determine what sort of finisher you really are. Luckily for us, Paul has more races to run. We can look confidently forward to him arriving at the scientific finish line, on time, looking ahead with anticipation to the next race. 
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