reality but often by expectations and hope on the part of the investigators, the general scientific community ... Theodore Friedmann. ASGT President, 2006â2007.
© The American Society of Gene Therapy
he “Rashomon effect” is a phenomenon in which a single event comes to take on a variety of realities and truths based on the conflicting perceptions of different observers. The term is derived from the classic Akira Kurosawa film Rashomon, which presents mutually contradictory accounts of a murder as seen and interpreted by four “eyewitnesses.” In science, as well as in crime, even with the best of intentions and rigor we occasionally see and believe what we want or expect to see rather than what is. A classic and fairly modern example of misleading perceptions in science is the early confusion regarding the correct number of chromosomes in the human karyotype. Even in the best scientific hands of the time, smudges in photomicrographs became chromosomes, partly because the conventional wisdom at the time had it that different human tissues could indeed have different numbers of chromosomes, and that is what some thought they should find. Only after the true human karyotype was established by Tjio and Levan in 1955 did it become clear that studies reporting variable and tissue-specific chromosome numbers—most of the time 48, sometimes 46, 45, or 47—were incorrect. We finally learned that photographic schmutz did not consist of genetic material. Gene therapy has been shaped not always by reality but often by expectations and hope on the part of the investigators, the general scientific community, the media, and the public. In that regard the history of this field may not be unique, but it certainly has become a modern poster child for the way reality can be bent by our expectations. And sitting in this chair during the past year has made it all the more impressive to me how far we have come during the past decade spanning the lifetime of this society and its journal, Molecular Therapy. In the period before the birth of this society ten years ago, many of us had come to believe that success would come fairly quickly, that clinical translation would be pretty straightforward, and—with our expectant and hopeful eyes—that’s what we sometimes saw. When the ASGT was born there had still been no clear therapeutic successes, common earlier
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perception notwithstanding, and we were just beginning to recover from the disappointments and misperceptions of the initial clinical applications from 1990 to 1995. Since then and during the lifetime of the ASGT, we have seen the maturation of gene transfer technology, the design of excellent clinical research studies, and, of course, the therapeutic successes in the X-SCID and ADA-SCID studies, promising clinical results in a broad set of cancer gene therapy studies, exciting effects of genetic correction in animal models of blindness and imminent human clinical studies of genetic forms of blindness, and even some hopeful findings in neurodegenerative, orthopedic, and cardiovascular disease, among others. But to some extent, perception and expectation in parts of the scientific and public media have swung far in the direction away from an acceptance of those results. Although most ASGT members are increasingly convinced of the validity of our current direction, the perception of gene therapy in important parts of the public media and even the general scientific community continues to be of expected failure and clinical ineffectiveness. Some remain unconvinced of the progress and disappointed by the time required to take concept to the clinic, despite the knowledge that other areas of indispensable modern medical technology such as tissue transplantation, cancer chemotherapy, and applications of monoclonal antibodies struggled for several decades in the limbo of setbacks, disbelief, and criticism. Remember that gene therapy has been in the clinic for only 17 years. Some observers still look at the same gene therapy reality that we do but perceive and interpret gene therapy in ways that expect failure and that emphasize the difficulties and technical hurdles still to be overcome rather than the reality that some of the rest of us see—unquestionable proof of therapeutic effect. Not necessarily “cures” yet, but certainly therapy. Some of us think that we see a forest—the maturation of the field from mere promise to clinical reality, early as it is. Some others see predominantly the trees—the setbacks, the reversals, and the problems. Eventually, more clinical successes and 1035
© The American Society of Gene Therapy
more effective education efforts by organizations such as the ASGT will change that perception. The ASGT has played a principal role in the evolution of gene therapy, not only through its individual members but as the principal public and professional voice for the field of gene therapy in the United States and even internationally. For its role as the proponent of what I think has been the most important perception of reality in this field, the ASGT
deserves congratulations and thanks from all of us for being the steady scientific shepherd of the field of gene therapy and for being its principal public voice during the past decade. It has been a privilege to help with this work as President during the past year.
Theodore Friedmann ASGT President, 2006–2007
www.moleculartherapy.org vol. 15 no. 6 june 2007