Paul C. Zamecnik (2011)

22 NOVEMBER 1912 * 27 OCTOBER 2009THE PROFOUND, lifelong passion Paul Zamecnik had for laboratory research and scientific discovery wavered only when his body could no longer keep at bay the fast-growing cancer that led to his death on 27 October 2009, at the age of ninety-six. Long after most people would have retired, Paul remained a hands-on researcher and maintained his own laboratory, sought the answers to basic scientific questions, and helped pilot the growth and development of the biotechnology company he founded for the purpose of translating antisense technology to develop innovative treatments for a broad range of diseases.Up until early September 2009, mere weeks before his death, Paul still went to work every day in his lab at Massachusetts General Hospital (MGH), accompanied by his daughter Karen Pierson, who had worked side by side with him for the past six years, much as Paul's wife of sixty-nine years, Mary, had worked for many years, preparing the cells he would need for his experiments, up until her death in 2005. Paul was driven to unravel scientific truths by an intrinsic quest for knowledge and an unquenchable curiosity. He was focused and selfmotivated and never got discouraged or sidetracked. In his pursuit of discovery and scientific knowledge, Paul would continually push forward, striking out in a new direction if one approach eluded him. He neither celebrated his successes - That looks interesting, he would observe in response to a positive outcome in the lab - nor dwelled on his disappointments.Paul was a true pioneer in the areas of biochemistry, nucleic acids, and protein synthesis. He was an innovator and a visionary, recognized most prominently for the discovery of transfer RNA (tRNA) and elucidation of the mechanism by which amino acids are transported to the ribosome and linked to form peptides. His legacy is equally remarkable for the recognition bestowed on him as the father of antisense, a novel approach that relies on short synthetic DNA chains to achieve selective inhibition of targeted gene expression. The discovery of the antisense mechanism for gene silencing gave rise to a powerful new research technique and a novel therapeutic strategy for treating infectious disease, cancer, and other ailments.Born in Cleveland, Ohio, in 1912, Paul decided early on that his interests and passion lay in science and medicine, although when he was a child baseball and the violin were the focus of his youthful energy. Paul demonstrated his brilliant mind and inquisitive nature at a young age, skipping a grade in school; although likely capable of skipping another, he did not because it would have put him in the same grade as his brother. Still, Paul was only sixteen when he went off to college, leaving his midwestern roots and selecting Dartmouth for his undergraduate studies because it would offer him a change of scenery and the opportunity to experience a more rural environment. This was during the Great Depression, and Paul was fortunate to receive a scholarship that covered the tuition at Dartmouth. He worked at one of the college's eating clubs, sweeping the floors in the dining hall, which earned him free meals.Paul completed his undergraduate education in three years, majoring in chemistry and zoology, and went on to complete the then two-year program of study at Dartmouth Medical School, where he lived with a group of other medical students in an unheated cabin kept warm by a wood-burning stove. Paul finished his medical studies at Harvard Medical School and received his M.D. degree in 1936.Newly married to Mary Connor, Paul applied to MGH for a surgical residency, but was put on the waiting list. One of his instructors at Harvard suggested that he talk to Dr. Joseph Aub, then the director of Huntington Memorial Hospital, a small cancer hospital owned by Harvard, about a residency position in oncology. During the interview, Joe Aub focused less on Paul's experience and interests in medicine and more on his willingness to teach Joe's daughters how to ski, making the assumption that because Paul had attended Dartmouth and lived in New Hampshire he must have been a good skier. …