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IN MEMORIAM Colleagues Remember Don Wiley, the Scientist and ManDon Wiley, a structural biologist at Harvard University whose brilliant research and personal warmth and authority impressed scientists across Harvard, the nation, and the world, was reported missing on Nov. 16 after a meeting in Memphis, Tenn. His car was found on a bridge spanning the Mississippi River. When his body was recovered downstream on Dec. 20, his death ruled an accident, the loss left a void in the scientific community and in the hearts of his many colleagues. Below are recollections from some of those people who worked closely with him at Harvard.
Don Wiley "With the tragic passing of Don Wiley, structural biology has lost one of its leading figures, renowned for his work in molecular immunology and virology. ...I feel a deep sense of personal loss of a friend and colleague, whose door was always open and whose creativity, pursuit of excellence, and enthusiasm for science touched me and everyone else who knew him. The memory of his bright charm and many accomplishments will remain with me and with his many friends and colleagues forever." --Jack Strominger, the Higgins professor of biochemistry, Harvard University
"Wiley was a crystallographer: this is the ultimate molecular biology. ...The image of a class I MHC protein with its peptide cargo firmly in place will stand as a landmark Wiley discovery that forever changed the field of immunology.... Asked by a colleague to expound on some biological question, Wiley demurred, saying: 'I'm sorry, but I just don't understand anything in biology unless I know what it looks like.' There is no better way to express crystallography's credo. ...We cannot say what scientific discoveries we have been deprived of by Don's death. But as a colleague, mentor, and friend he is irreplaceable." --Hidde Ploegh, the Edward Mallinckrodt Jr. professor of immunopathology, HMS
"I can still see Don on my morning run. As I jog along Memorial Drive, I see him striding along, his children in each hand as he guided them to school. He seemed so very happy, and I was always heartened to wave hello and then consider his enormous contributions to medicine and biology. I was introduced to him some years ago by Steve Harrison and Fred Rosen at a time when we were creating the Howard Hughes program at the Children's Hospital. HHMI wanted to appoint Steve and Don as investigators, and the HHMI lawyers insisted that they must have a hospital affiliation. It was my delightful task to invite them to join us at Children's. That's when I began to appreciate the power of Don's mind, his uncluttered approach to science, his straightforward and totally honest dealings with his colleagues, and his capacity to be a team player. My heart goes out to his family, his colleagues, and the world of medical science." --David G. Nathan, the Robert A. Stranahan distinguished professor of pediatrics, HMS and Children's Hospital
"Don was a first-year assistant professor when I was a first-year graduate student in 1971. Aside from Jack Strominger, the only other rotation I did was in Don's lab. I did not accomplish much, aside from helping him set up the lab. I had the idea that because there were lots of sequences for immunoglobulin variable domains, it should be possible to predict something about their structure, but that was impossible at the time. One evening we were talking, and Don got philosophical. He said, 'Tim, do you think you will ever make a difference?' Having few qualifications other than confidence in myself, I said, 'Yes.' He said that was interesting that I thought I would, because few people did, and he was going to write it down. About 25 years later, I was giving a seminar in Don's department and met him in his office. He said, 'Did we make a bet when you were a grad student here? I have a piece of paper in my desk drawer, I know just where it is, and it says, "Tim Springer will make a difference." Do you still think that's true?' Don meant much to me as a teacher and colleague. His honesty, wit, energy, enthusiasm, commitment to work only on the most important and challenging problems, and friendship are qualities I will always remember and sorely miss. I am deeply saddened that he has been taken from us. I extend my profound sympathy to his students, colleagues, and family." --Timothy Springer, the Latham Family professor of pathology, HMS and the Center for Blood Research
"Don was a wonderful colleague and friend. He had an infectious enthusiasm for science, and a brilliant analytical mind. We worked closely together for six years on MHC molecules in autoimmune diseases, and Don deeply cared about clinically relevant research even though his own work was very basic. I remember many long, lively conversations with Don, and he had a remarkable ability to get to the core of a scientific problem. Don made a lasting impression on me with his commitment, brilliance, and honesty." --Kai Wucherpfennig, HMS associate professor of neurology, Dana-Farber Cancer Institute
"By the time I took my first immunology course, much of the Wiley/Strominger work on the MHC had already become dogma, just several years after its publication. Although Don will always be remembered for his tremendous scientific contributions in several fields, I will also think of his warmth, charisma, and enjoyment of science. He set forth many positive examples for his students, including his pursuit of key scientific questions, his exceptionally clear presentations and publications, and his genuine care for everyone in his lab. From the first day that I began to collaborate with his lab, Don was a wonderful teacher and always found time in his busy schedule for his students. I will continue to be influenced by him and feel very fortunate to have had the opportunity to work with Don and to have known him." --Benjamin Gewurz, research assistant in pathology, HMS
"I first encountered Don Wiley when I hopped the M2 shuttle to Harvard College to hear his seminar describing the first structure of a human histocompatibility antigen, the cell surface proteins that present foreign antigens to our immune system. During that Technicolor tour de force, Don captivated his audience with his bubbling enthusiasm for what was clearly a labor of love. Peering at us over his glasses, Don's eyes would light up as he described the intricacies of the structure. This was a trademark of Don's scientific presentations. His boyish enthusiasm for science made us realize we're in the best of all possible professions, in which every week brings new challenges and any difficulties are overshadowed by the exciting discoveries made by students and postdoctoral fellows in our laboratories. He made it look easy, and I became hooked on the idea of visualizing protein structures by x-ray crystallography. I am still reminded of those riveting glimpses of the MHC protein whenever I confront a newly determined structure in my own laboratory. Don's fervor was not limited to science. He regularly held court with the students and postdocs of the Wiley and Harrison laboratories during afternoon tea, passionately discussing politics and world events and reminding us of the complicated world outside Harvard's ivory towers. He could at once confront an opposing viewpoint with a lucid analysis of the facts and show compassionate support for the person holding that view, however flawed. Don was an ambassador for our profession who quietly taught and led by example legions of young scientists. Their successes are the enduring proof of his great mentoring abilities. He is sorely missed by us all." --Tom Ellenberger, the Hsien Wu and Daisy Yen Wu professor of biological chemistry and molecular pharmacology, HMS
"I joined Don's lab in the fall of 1977 to work on influenza virus hemagglutinin in collaboration with Sir John Skehel, Mill Hill, London. Four adventurous years later, the structure was determined and it revealed the structural basis of how antigenic variation in influenza virus led to new epidemic strains and how this information could be utilized to help decide when a new flu vaccine was needed. The time in Don's lab was as exciting as one could ever dream of in a scientific endeavor. His constant boyish enthusiasm, the high quality of this scientific problem, and the strong drive to succeed in what was an extremely challenging project at the time--a 220 kDa glycoprotein consisting of 25 percent carbohydrate--resulted in a once-in-a-lifetime opportunity. The rest is history, since this fascinating project was to occupy Don's attention for the next 20 or so years and lead to groundbreaking discoveries on how enveloped viruses fuse their membranes with the host cell in order to facilitate viral entry. These pioneering studies on viral membrane fusion were further enhanced by his structures of the fusion domains of HIV-1 and Ebola virus. Don always chose quality problems, and the impact of this work was enormous in virology. His contributions to immunology were equally monumental through his structural studies on MHC molecules, the T cell receptor, and NK receptors. Such innovative structural investigations were the hallmark of his work that has made a profound influence on our understanding of key processes in immune recognition and viral pathogenesis. His boundless enthusiasm for science will be sorely missed." --Ian Wilson, professor of molecular biology, Scripps Research Institute
"Don had invited us to his home in Concord to celebrate Christmas in a get-together for all members of his and Steve [Harrison]'s lab. It was my first winter in Boston, and till today, I vividly recall the design of his home, the great views of the woods surrounding his house and the hearty welcome we all received at the party. I remember thinking that this fellow must have class and be something special. This first impression could not have been closer to the truth. Years later, I heard Don presenting his latest work on the structure of MHC to an audience of cell biologists with little background in immunology. It was simply stunning to watch him present his talk--he was like a magician, providing structural and conceptual elements of the work with the aid of remarkably simple (but nevertheless profound) overheads, in what seemed to all of us a magnificently choreographed act. Don's class, his fantastic intellectual caliber, and clarity of mind came across whenever talking to him, hearing about him, or reading his work." --Tom Kirchhausen, HMS professor of cell biology, Center for Blood Research
"Don Wiley was one of the most brilliant scientists I have known. To have him as a colleague was a great attraction when I considered moving to Harvard. I remember the recruitment dinner with him and other faculty. He was the center of the conversation with his witty remarks, and he convinced me that this university was the place I wanted to be. Later on I was impressed by the way he valued his students. He pointed out how smart they were and what he had learned from them. I myself learned something new in almost every conversation I had with him. I was on his site-visit team in Memphis last fall. He drove me from the airport to the hotel and pointed me to all the attractions of the town, including the spectacular view over the Mississippi River glittering in the afternoon sun and the parade of ducks in the Peabody Hotel. That's what I will remember. He was a wonderful person." --Gerhard Wagner, the Elkan Blout professor of biological chemistry and molecular pharmacology, HMS
"Don Wiley was an inspiring mentor, colleague, and leader in both the Harvard and worldwide virology communities. His undergraduate teaching encouraged our students to pursue work in basic biochemistry, molecular cell biology, virology, and immunology. At the graduate level, Don participated freely in every aspect of the Harvard Virology Program. He interviewed applicants, lectured at recruitment weekends, served on preliminary examination committees, attended retreats, presented his research at poster sessions and seminars, supported students for laboratory rotations, encouraged students to do rotations in his laboratory to learn more about structural biology, and worked closely with his PhD research students. He contributed with a free and engaging spirit to the intellectual life of this program. Don will be forever known for his scientific discoveries. Two are particularly outstanding. His group's research with John Skehel on the structures of the influenza hemagglutinin provides seminal insight into the mechanisms by which enveloped viruses fuse with cell membranes and enable virus nucleic acid to enter the cell cytoplasm. Don's group extended these concepts by showing that HIV and other membrane interactive glycoproteins and proteins undergo similar transitions. Second, his research with Jack Strominger's group resulted in stunning images of how antigens are presented in the context of class I histocompatibility molecules; this revolutionized our understanding of T cell-receptor recognition of foreign proteins. Despite wide recognition of his outstanding scientific and educational accomplishments, Don remained "unfazed." He was always preoccupied with his most recent experiments, his current students, and his ongoing academic work. He thoroughly enjoyed research and strove to stay on the frontiers by applying his entire intellect and energy to his scientific interactions. A key to his great success was his ability to maintain a sense of humor and measure in all his human interactions. His creative spirit and personal presence will be forever missed by his colleagues at all levels." --Elliott Kieff, the Harriet Ryan Albee Professor of Medicine, HMS and Brigham and Women's Hospital, and Virology Program chair
"It is with great sadness that I sit down to remember my PhD mentor, Dr. Don Wiley. Don was truly an exceptional, larger-than-life scientist. He was brilliant. He was insightful. He was rigorous. He left us breathtaking structures of proteins that decorate microbial pathogens and immune cells and provided us with insights into complex processes including virus entry, antigen recognition, and immune surveillance. To those of us who had the honor of working under his tutelage, Don Wiley was an inspiring mentor. He was demanding but, at the same time, he filled us with endless enthusiasm for science. What was really special about Don was his absolutely genuine 'kid in the candy store' glee with the discovery process. Two personal examples stand out: when I stood by the microscope when he first saw his influenza hemagglutinin crystals coated with red blood cells (proof of their biological activity) and when he first showed me the location of the fusion peptide in the native hemagglutinin structure. I can still picture and hear his animated discourses at such times! He will be sorely missed." --Judith White, professor of cell biology and of microbiology, University of Virginia
"I was Don's second graduate student, joining his lab just after Judy White, his first graduate student, finished her thesis. The lab was small then, but was an intense and exciting place to be--Don had a compelling vision that one could use protein crystallography to address fundamental problems in human health. When I joined the lab, Don and his first postdoc Ian Wilson were hard at work on the structure of flu virus hemagglutinin, a viral antigen. Class I MHC proteins had been shown to be recognized together with viral antigens by T lymphocytes, so an MHC protein was the next logical target. I started work on HLA-A2, a human class I MHC molecule, a project that was to be hampered for years by small amounts of protein and small, thin crystals. When I think back, I am amazed that Don did not urge me to do something that would have been more productive for his lab. He must have had grants to worry about (this was well before the days of HHMI funding), and the HLA project went nowhere for many years. But he never acted impatient or annoyed about the lack of progress. Instead, in his own inimitable fashion, he was excited about every small step forward and was completely confident that the structure could and would be solved. This attitude marked Don's approach to all projects and was encouraging and inspirational to everyone who had the privilege of working with him. Don was one of a kind--he can never be replaced and will be missed by the whole scientific community, but especially by the past and present members of his lab." --Pamela Bjorkman, professor of biology, Howard Hughes Medical Institute and California Institute of Technology |
