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IN this issue of Anesthesiology, we mark the beginning of another annual event. Last year, for the first time, the Journal published a “special issue” containing manuscripts of research presented at the Anesthesiology-sponsored Symposium at the Annual Meeting of the American Society of Anesthesiologists. In an accompanying editorial, the Editor-in-Chief, Michael M. Todd, M.D., stated his hope that the issue would be the first in a series of annual special issues. In the present issue, we feature 10 manuscripts based (in part) on research presented at the 2004 Journal-sponsored Symposium, “Pharmacogenomics and Anesthesia: Determinants of Individual Response and Outcome.” This being the first anniversary of the special issue, we can now inaugurate it as an annual event.
The Journal Symposium examined the application of recent advances in pharmacogenetics to anesthesia, with a focus on how genetic variability affects our patients’ response to drugs. Pharmacogenetic variability may influence drug metabolism, drug transport, receptor structure and function, cell signaling, and the myriad of downstream responses we perceive in daily practice. The past few years (we’re now a decade into the “postgenome” era) have witnessed explosive growth in technological capabilities, genome mapping, molecular and human genetics, computational biology, and “omics.” In addition to pharmacogenomics, we have functional and structural genomics, transcriptomics, proteomics, metabolomics, and others. The exponential increase in this research is evidenced by simply viewing the articles indexed in MEDLINE that address pharmacogenetics and pharmacogenomics (fig. 1).
Fig. 1. Annual citations in PubMed listed in response to the search terms pharmacogenetics or pharmacogenomics.
Fig. 1. Annual citations in PubMed listed in response to the search terms pharmacogenetics or pharmacogenomics.
Yet what is new, is old. Sir William Osler, in 1892, said, “If it were not for the great variability among individuals, medicine might as well be a science and not an art.” The term pharmacogenetics dates back to 1959.1Anesthesiology as a specialty provided some of the first insights into the clinical impact of pharmacogenetics. Prolonged apnea after succinylcholine, thiopental-induced acute porphyria, and malignant hyperthermia were clinical problems of the 1960s whose investigation helped craft the developing new science of pharmacogenetics. Today we perhaps take for granted the knowledge that they are genetically-based problems, due to variants in pseudocholinesterase, deficient heme synthesis, and the ryanodine receptor, respectively. Reading the first reports of these problems gives insight into how far we have progressed. The cover of this month’s Anesthesiology exemplifies this progress, depicting the ryanodine receptor gene and the myriad polymorphisms that have been identified to date.
Some of the greatest challenges of the “postgenome era” will be managing the unprecedented amount of information generated, educating physicians to understand and use the new biology, communicating new knowledge to clinicians and patients, and translating it into clinical advances. Towards that aim, Anesthesiology chose “Pharmacogenomics and Anesthesia” as the theme for the 2004 Symposium. The Symposium featured lectures on “Pharmacogenomics of Drug Disposition,” by Kenneth Thummel, Ph.D. (Professor of Pharmaceutics and Associate Dean for Research, University of Washington School of Pharmacy, Seattle, Washington); “Autonomic Nervous System Pharmacogenomics,” by Paul A. Insel, M.D. (Professor of Pharmacology and Medicine and Director of the Medical Scientist [M.D.-Ph.D.] Training Program, University of California, San Diego, California); and “Pharmacogenetics of Responses to Cardiovascular Drugs,” by Brian Donahue, M.D., Ph.D. (Assistant Professor of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee). All of these speakers graciously agreed to be recorded and provide their slides, and we are pleased to offer their presentations as a Web Enhancement to this month’s issue.
In addition to these plenary lectures, there were 16 posters selected for presentation at the Symposium. These authors were invited to submit a formal manuscript relating to their work, which underwent peer review. In this issue we feature 10 such articles, along with a review article. The topics include genetic influences on drug disposition, responses to various drugs across several classes, and receptor polymorphisms, and the articles represent authors from eight countries—truly an international effort. The goal of Journal Symposia is to feature dynamic areas and new research relevant to anesthesiology, and to stimulate investigators and encourage the publication of such work in Anesthesiology. We invite you to read the fruits of such efforts in this month’s issue.
The next Journal Symposium will be “Plasticity in Postoperative Pain,” organized by Timothy J. Brennan, Ph.D., M.D. (Associate Professor, Department of Anesthesia, The University of Iowa, Iowa City, Iowa), and Srinivasa N. Raja, M.D. (Professor, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland). We look forward to this Symposium, and to next year’s annual Symposium issue.
Assistant Dean for Clinical Research, Professor and Research Director, Department of Anesthesiology, and Professor of Medicinal Chemistry (Adjunct), University of Washington, Seattle, Washington. kharasch@u.washington.edu
