Lost - and found - in translation.

Valued colleagues and friends, thank you for the extraordinary privilege of serving as the 101st ASCI president. To stand before this distinguished group of physician-scientists without a PowerPoint presentation full of data slides is a deeply uncomfortable position. I do not stand before you with the data of graphs, charts, and models, but rather with the data of experience acquired through a journey from the clinic to the lab, and with the hope of fulfilling a promise. As you have probably guessed from the title, this talk will focus on the challenge of translational medicine: what it means (or doesn’t) and the inadvertent obstacles we may have in fact created, including an assessment of the roadblocks that lie ahead. I can think of no topic more important to address in front of this audience than to ask what is the ASCI’s role and responsibility in guiding the transformation of medicine through science to improve the lives of patients. This society is not about “establishment” or orthodoxy. The ASCI was founded on noble principles: insistence on excellence, skepticism, impatience with status quo, and the belief that science can and must transform the lives of patients. These are the very attributes that make us uniquely suited to guide this transition in medicine. It is true ASCI membership, because of its honorific status, could be conceived by some to be the very essence of establishment. However, that is not what I have seen; that is not our ASCI. The willingness of my ASCI colleagues to question and to ask can we do it better lends great confidence in our ability to face the challenges ahead. In Joel Howell’s beautifully written history of the ASCI (1), we learn that the physician-scientists who gathered for the first ASCI meeting considered themselves to be colleagues, friends, and fellow revolutionaries with the shared goal of “moving clinical research towards a scientific basis grounded . . . in new more progressive sciences.” Is there a more appropriate definition for translational medicine and a clearer delineation of ASCI’s role in fostering it? In an era where genomics, genetics, epigenetics, and proteomics are transforming our landscape of disease, is it not crystal clear that the very DNA and spirit of the ASCI lie in using these new tools towards better understanding disease and improving the diagnosis and treatment of patients? Please permit a short personal detour, which I hope will place the rest of this talk in context. I am the son of a philosophy professor, Theodore Mischel, who lived in a library of 3,000 books that he constructed in our home; I wanted to live in that library with him. When he was 51 and I 14, he developed severe stomach pain. Before I could grasp what was happening, I watched as my formerly robust father was transformed into a stomach cancer patient and a dying man. Perhaps the most painful part was the fallacy of hope that chemotherapy offered — we all spoke with optimism about how this would make him better, while watching him writhe in pain, shrink in form, and struggle to keep his dignity. I recently read Abraham Verghese’s brilliant novel Cutting for Stone (2). If you haven’t read it, I urge you to do so. In the middle of the book, the main character, a 15-year-old boy, a twin like me, who had suffered the loss of his parents, wanders through the medical library of his adoptive father taking comfort in the medical volumes on the shelf. I read these words with disbelief. How could Dr. Verghese have gotten it so right? The medical library of my Uncle Charles (a medical student at the time) brought order, comfort, and hope. Harrison’s textbook of internal medicine Principles of Internal Medicine was a balm to my soul. I made myself a promise to become a physician-scientist to try to help people with cancer. Do not most of us in this room share similar stories, motivations, and promises? Lost in translation — a flawed construct? We are not alone in our belief and hope that the lives of patients will be directly improved through science, much of it done by the people in this room. The NIH has devoted considerable resources to establishing translational research centers; medical schools and universities have developed translational research training programs. New medical journals specifically designed to cover translational science are arising at an astonishing pace. Yet clear and coherent definitions of translational medicine are lacking. Translational medicine means different things to different people. To molecularly based scientists, it means bridging the gap between basic and clinical sciences, i.e., transforming knowledge derived through basic science investigation into improved diagnosis and treatment of patients in a bench-to-bedside flow of information. To health care delivery scientists, it means translating knowledge about individuals into populations, to close the gap in the access and delivery of new treatment options. The lack of clarity regarding translational medicine is not just an issue of semantics. The constructs we use, i.e., the conceptual elements by which we define things, have broad impact on how we judge them. Our current construct of translational medicine creates two specific unintended and serious problems. (a) The novelty/creativity problem: In an increasingly competitive scientific landscape, novelty is an essential ingredient for publishing in high-impact journals, including our own journal, the JCI. Elite physicianscientists, like the ones in this room, aim to do work that is creative, original, and not derivative. By defining translational medicine as bridging the gap between basic and clinical, are we not relegating it to a derivative status? It sounds more like moving preestablished goods along a conveyer belt to their next destination than it does participating in exciting, open-ended discovery. Who in this room really wants to spend their time translating stuff that has already been done by others, simply moving it into This article is adapted from a presentation at the ASCI/ AAP Joint Meeting, April 16, 2011, in Chicago, Illinois, USA.