Grand Rounds-”The Joys of Translational Research”

December 11, 2007

Bellevue AmphitheaterCommentary By: Benjamin Bergman PGY-2

This week’s Grand Rounds lecture was delivered by Dr. Barry Coller, a graduate of our own internal medicine program in 1972. He completed advanced training in hematology and clinical pathology at the National Institutes of Health and is currently the David Rockefeller Professor of Medicine, Head of the Laboratory of Blood and Vascular Biology, and Physician-in-Chief of The Rockefeller University Hospital. Dr. Coller’s research interests have focused on hemostasis and thrombosis, in particular platelet physiology.  He developed a monoclonal antibody that inhibits platelet function; a derivative of that antibody, abciximab, was approved for human use by the FDA in 1994. As we all know, it is now in clinical use to prevent ischemic complications of percutaneous coronary interventions.

Dr. Coller’s talk illustrated the importance of research methodology vis-a-vis platelet physiology and coronary artery disease. He stated that the four primary responsibilities in academic medicine are patient care, education, research, and world health, with the latter including social justice.  Medical research is critical to achieve all of these goals.

Dr. Coller went on to present his initial studies of platelet function and how it led to his current work in platelet assays and pharmacologic treatment of coronary artery thrombosis.  In some of his early work Dr. Coller studied Glanzmann thrombasthenia and polymorphisms in the genes encoding glycoprotein αIIbβ3 (formerly known as GPIIbIIIa) which are responsible for this disease.  He then went on to discuss mechanisms of thrombosis, including the role of fibrinogen, von Willebrand’s factor, and finally, his cell of interest, the platelet.  αIIbβ3 plays a central role in platelet aggregation as a polyvalent transmembrane platelet surface protein that allows platelets to bind one another.  He described his translation research approach, using the benefits of small molecules and drug discovery that led to the development of a chimeric monoclonal antibody, now marketed as abciximab.  When added to normal platelets, abciximab produces platelet aggregation identical to that observed in patients with Glanzmann thrombasthenia.

Dr. Coller articulated the essential skills of the translation research team.  These skills include the ability to: 1. articulate a health need and address it with a basic science hypothesis, 2. create a robust assay to address the hypothesis, and 3. conceptually design an ethical and feasible phase three study before embarking on a project.  Utilizing these criteria, he has been able to design an assay for platelet function, in which whole blood is mixed with fibrinogen-coated beads.  He has demonstrated that there is a wide variation in the platelet inhibition achieved amongst a group of individuals given 900 milligrams of clopidogrel, leading to the idea that one day we may have pharmacologically tailored therapy for acute coronary syndromes.

But perhaps the most powerful message espoused by Dr. Coller was that our current model of physicians and research has excluded research from the physician’s realm.  He strongly disagrees with the idea that “science is done by scientists,” while doctors take care of patients.  Noting that current medical curriculum does not emphasize research, and that it is usually pursued extracurricularly, Dr. Coller put forward that “it should be instilled into the minds of medical students that they have an ethical obligation to discover.”  The lecture ended on this inspiring note.

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