Translational medical research.

Abstract

JUST 1 YEAR AGO, IN AN EDITORIAL INTRODUCING A THEME issue on “Basic Science and Translational Research in JAMA,” we stated, “The magnitude, scope, sophistication, and funding support for biomedical research are unprecedented and continue to increase dramatically.” That statement is even more true today. The National Institutes of Health funding has doubled during the past decade; the initial sequence and analysis of the human genome was published in 2001; and advances in neuroscience, molecular medicine, diagnostic radiology, robotic surgery, pharmacology, and many other areas herald the application of basic science to clinical medicine. Except for theme issues, articles reporting the results of basic science investigations or preclinical translational research have seldom been published in JAMA. However, it is important for physicians and other health care professionals to maintain an awareness of important scientific advances and promising discoveries in biomedical research. Accordingly, in this issue of THE JOURNAL, we are introducing a new section on Translational Medical Research. This section is intended to provide a forum for publication of basic science and translational research studies, with emphasis on studies of novel discoveries that advance the understanding of disease mechanisms and provide insights that may prove helpful in improving the diagnosis, treatment, and prevention of common diseases and conditions. The first article in this section illustrates a series of elegant investigations by Imai and colleagues that explore possible mechanisms underlying a highly lethal syndrome in critically ill patients. The authors began with the important clinical observation that patients with acute respiratory distress syndrome (ARDS) often experience multiple organ dysfunction and postulated that an injurious ventilatory strategy may lead to end-organ epithelial cell apoptosis and organ dysfunction. Using an in vivo animal model of aspiration, Imai et al demonstrated that an injurious ventilatory strategy increased epithelial cell apoptosis in the kidney (especially in LLC-RK1 renal tubular cells) and the small intestine and led to increased levels of biochemical markers indicating renal dysfunction. Then, in an in vitro model, the authors used plasma from the ventilated animals and induced apoptosis in LLC-RK1 renal tubular cells and found that a fusion protein that blocks soluble Fas ligand (a circulating pro-apoptotic factor) attenuated apoptosis induction. Finally, in an investigation using samples from patients previously involved in a clinical trial of a lung protective strategy, the authors found a significant correlation between changes in soluble Fas ligand and changes in creatinine in patients with ARDS. Investigations such as this and other translational research studies often reflect a “bench to bedside” or a “bedside to bench and back to bedside” approach that begins with a challenging clinical problem or observation, involves rigorous investigation with application of basic science techniques and discoveries, and brings new insights about important clinical problems back to the clinical interface, along with potential directions for the next steps in future research. Perhaps more important, most translational research studies require close collaboration between basic scientists and clinical researchers, with synergistic effects resulting from shared expertise and dedicated efforts to solve challenging problems. Although the clinical research enterprise currently is facing several important challenges, breakthrough discoveries in basic biomedical science must continue to be translated effectively to human studies to advance clinical science, expand medical knowledge, and ultimately improve patient care and health. We encourage authors to submit studies of rigorous, highquality basic science and translational research that extend along the “bedside to bench” and “bench to bedside” continuum for consideration for publication in the Translational Medical Research section of THE JOURNAL. Our goal is to encourage investigators to report their research and enable clinicians to gain broader insight about basic mechanisms of disease that will ultimately lead to better care of patients.