This year’s honorees tell us how far we have come in the cell death field. Both started their careers studying cell death, but it has always been obvious that, even in the narrowest definition that cell death could be programmed, the program had to be initiated somehow; even if cell death proved to be a clock ticking down from some starting point, that starting point had to be defined, and it was extremely unlikely that the point of initiation would be the last telophase or other step in the life cycle of a cell. Even in Caenorhabditis, in which some cells are born only to die before differentiating into a neuron or other identifiable cell type, one had to assume that the death would result from some sort of internal metabolic failure. For metamorphosis, part of the definition of programming included recognition that cell death was triggered in amphibia by hormones and in insects by hormones and neural signals.
Raymond Birge has followed that logic to the extent that they now can be considered to work more on cell signaling. Raymond is Editor-in-Chief of Cell Communication and Signaling (a sponsor of this meeting and a journal that solicits articles addressing apoptosis). Thus, while there are many secrets still to be understood concerning the internal workings of how cells die, by apoptosis, necroptosis, pyroptosis, ferroptosis, or other means, we are now also focused on what extracellular and intracellular signals determine the point at which a cell turns down an increasingly irreversible path toward death.
In the mid-1990’s, Michael Hengartner, Zahra Zakeri, and I missed a connecting flight to a meeting and sat talking in Albany, New York, considering the growing field of apoptosis and the possibility of organizing a discussion group for New York area scientists. At the meeting, at Lake Placid, NY, Zahra mentioned the idea to Raymond Birge, then a postdoctoral fellow in the laboratory of Hidesaburo Hanafusa at Rockefeller University (where he subsequently became an Assistant Professor), and, pointing out that Manhattan would be a more convenient meeting place than Queens, NY, he said, “I think that I can help.” That carried the original meetings at Queens College in 1996 and 1998 to a monthly gathering at Rockefeller. The Rockefeller meetings were so enthusiastically received that they finally gave rise to the International Cell Death Society. Throughout all this time Ray has devoted considerable time to the Society, nurturing it, helping to find speakers, seeking financial support, and in general being a major contributor to the success of the Society.
These comments are intended to thank him for his huge contributions over these last 28 years, but in no way diminish recognition of his contributions to research in the field of cell death. Always interested in signaling mechanisms, he first began to look at the phosphatidylserine (PS) manifested by dying cells and how it encouraged efferocytosis, or engulfment of apoptotic fragments by phagocytes. This exploration led him to the realization that the TAM (Tyro3, Axl, and Mertk) family of receptor tyrosine kinases, dysregulated in many cancers, fosters an immunosuppressive environment that prevents the development of an immune response that would kill the malignant cells. (Of course, in the absence of cancer, suppression of the immune response prevents the body from reacting to the frequent death of cells from turnover processes or injury.) He has continued to explore the many ways in which TAM tyrosine kinases regulate immune suppression and the progression of cancer. From these studies, he has branched to address immune suppression and stimulation more generally, asking what happens when apoptotic cells meet phagocytes. This has led him to the study of Crk (CT10 Regulator of Kinase, an adapter protein that binds to several tyrosine-phosphorylated proteins). He has learned that Crk is important for both metastasis and tumor immunogenicity. Today he presents an overall view of the function of PS, PS receptors, and the lifestyle of tumors. His research has led to the possibility of attacking tumors by attacking the means through which they interact with phagocytes and surrounding cells. It is a fascinating, exciting, and complex story. Ray is a distinguished scientist who is Professor of Biochemistry and Member of the New Jersey Medical School Cancer Center. He is currently on the editorial board of The Journal of Biological Chemistry, Frontiers in Immunology, and Editor-in-Chief for Cell Communication and Signaling, which helps support our meeting. Today we are pleased to recognize a major contributor to our society, outstanding scientist, and dear friend.