(236a) The Inconsequentiality Of Having Brilliant Graduate Students For Studying Blood-Surface Interactions

Ed Leonard has been an educator, innovator and creative thinker in a vast array of scientific areas. I will focus on his contributions in the area of blood-surface interactions, a field in which he retains interest to this day and which remains, in many ways, a frontier. Let me first focus on his role as an educator. As a novice graduate student at Columbia back in rebellious 60's of Mark Rudd fame, little of any note was known about the sequence of events that occurred when blood contacted a foreign surface. It was known that cells and proteinaceous deposits adhered to the surface, grew into large masses and these eventually blocked the flow of blood through the ?artificial device.? Sometimes these masses broke off, ending up lodged in some part of the vascular system, potentially leading to a stroke, heart attack or some other pathological abnormality. What blood elements were involved, how they interacted to form the thrombotic masses and the extent to which blood flow modulated such events was a subject of great mystery. In order to attack this problem, Ed quickly realized that his room full of chemical engineering graduate students would not be enough to begin to understand this highly interdisciplinary problem. Exposure to a broader range of academic specialties was required. Ed providently took advantage of a seminar series that was funded at the time by the University and established the Biomaterials Seminar. This meeting was held monthly and consisted of a reception, a dinner, an invited speaker and a cast of the leading experts in this nascent field, from such disciplines as surgery, hematology, materials science, biochemistry, and various engineering fields. Of course there was the requisite crew of motley graduate students, who had the glorious opportunity to rub elbows with the leading thinkers in this field at all the events. Together we explored the mysteries of thrombosis, the underlying paradigms that ruled each discipline and the biases and ignorance that each specialization harbors about other far removed specializations. The rules were simple - students and experts were equal, anyone could ask a question and no question was considered inappropriate. After all, outside of a particular discipline, we were all basically neophytes. The speaker was informed that the object was for all to learn, not for him or her to present their doctrine - in fact, rarely did speakers finish their talk and the best talks were often those that only got through a few slides and had to revisit to finish. The interaction of students, faculty, scientists and industry representatives was a learning experience that remains with me to this day and has served me well in my career. Although I have tried, I have not been able to duplicate such an environment. In many ways it was a much more important educational vehicle than all the formal educational courses that I was exposed to throughout my stay at Columbia and Ed Leonard was clearly the driving force behind this forum over more than a 10 year period. What did we find out? And how did I use the knowledge? And what remains to be achieved? Well, we found out that things were hard in the area of thrombosis. To this day, small vessel prostheses of biomaterials cannot be used; the total artificial heart remains on the drawing board and newly developed inhibitors of thrombosis have been very limited despite the billions of $$$ spent by pharmaceutical companies to produce them. The simplest and best advice is ?take an aspirin.? But our knowledge of the process has grown and the importance of basic chemical engineering transport concepts has expanded greatly due to the pioneering work of engineers, like Ed. Studies first initiated in Ed's lab have revealed the importance of the red blood cell in modulating the transport and reaction of platelets to and with surfaces; the ability of the shear forces to activate such cells, such that they grow more rapidly and larger; and the ability of these same forces to embolize parts of the growing masses to downstream locations with its pathological consequences. Shear stress has transitioned from a term virtually unknown in the medical literature to one that permeates many medical fields and has become an important parameter for understanding the nature of certain bleeding disorders, the ability of white cells to attach to and cross vascular endothelium, and the regulation of vascular stenoses, including plaque rupture, to name a few areas. Clearly, Ed's interest, probing studies and quick, analytical mind laid the foundation for such advances. It will be an honor to discuss the ways in which my career was directed both practically and intellectually by my early exposure to the environment and mentoring in Ed's lab.