E.B. Wilson Medalist, 1988

Elizabeth D. Hay has been selected as the 1988 recipient of the highest award of The American Society for Cell Biology-the E. B. Wilson Medal. She received the award and delivered an address on her work at the joint meeting of the ASCB with the American Society for Biochemistry and Molecular Biology in February 1989. Betty Hay is a colorful, individualistic woman who has contributed to contemporary biology both as a creative laboratory scientist and a tireless leader in three different disciplines: cell biology, anatomy, and developmental biology. Betty came from Florida and graduated with honors from Smith College, where she began to work on amphibian limb regeneration with Professor S. Meryl Rose. After receiving the M.D. from Johns Hopkins she served as a medical intern at the Johns Hopkins Hospital. She continued her laboratory research as a medical student and then as a faculty member, first at Johns Hopkins, briefly at Cornell, and since 1960 at Harvard Medical School. Betty was drawn to research by an interest in the complex cellular and biochemical events that take place during the regeneration of an amphibian limb. This system presented an experimental microcosm of many of the processes involving mesenchymal and epithelial cells that also occur during normal embryonic development. This interplay between the mesenchyme and epithelia has been the focus of Betty's research. She and her students clarified the cellular origin of blastema cells and osteoclasts in the regenerating limb, the production of extracellular matrix by embryonic epithelial cells, and the inductive influence of the extracellular matrix on the differentiation of epithelial cells. In the early 1960s Betty and Don Fischman, then a medical student at Cornell, provided strong evidence that during limb regeneration mononuclear leukocytes are the precursors of the bone-eating cells called osteoclasts. They showed that these ceils fused together to form multinucleated cells. Others went on to show that a lack of these precursors is responsible for the fatal congenital disease called osteopetrosis that is now treated by transplantation of these precursor cells. Later in the 1960s Betty, Jean-Paul Revel, and other colleagues provided the first evidence that epithelial cells can produce and secrete components of the extracellular matrix such as collagen. This was really a startling revelation since the very strong conventional wisdom had it that the extracellular matrix was made only by mesenchymal cells such as fibroblasts and chondrocytes. Consequently, the very thought that epithelia make collagen was heresy of major proportions. The evidence for this new concept came from several directions. From electron microscopic studies on the developing cornea they correctly identified the epithelium as the cell of origin of the underlying extracellular matrix. This work was included in a monumental monograph "Fine Structure of the Developing Avian Cornea S a book that launched the avian cornea as an object of serious experimental investigation. Confirmation that epithelia produce matrix came from experiments with isolated epithelia and neural tubes in tissue culture. During the 1970s Betty and her colleagues produced a series of papers showing that molecules of the extracellular matrix, including several types of collagen, influence the differentiation of epithelial cells. This is the flip side of their previous work on extracellular matrix production by the epithelium. They found that the matrix itself stimulates production of more matrix by isolated corneal epithelium. Currently she is analyzing the effects of extracellular matrix on the transformation of epithelial cells to mesenchymal cells. Together with related studies in other laboratories, her work on the inductive effects of extracellular matrix on various tissues started one of the major trends in cell biology that continues to this day. Betty has generally run a small research group so that she could maintain hands-on personal involvement in the research. From my student and faculty days at Harvard Medical School, my strongest memories of Betty in action in the lab are of her working side by side with a student or postdoctoral fellow at the tissue culture hood. It may be significant that both of the previous Wilson Awardees whom I have seen at work-Hugh Huxley and Joe Gall-are also hands-on bench scientists to this day. Students may find this a refreshing revelation in this day of large research groups. Beyond keeping busy in the lab, Betty also fostered a marvelous sense of community in her group. The daily lunches were livened up by such things as Betty cooking up her latest collection of wild mushrooms or challenging her young colleagues to a spirited game of cards. This outstanding research productivity is all the more remarkable when taken together with Betty's tireless contributions to the scientific community. She has served as the president of three major societies: The American Society for Cell Biology, the Society for Developmental Biology, and the American Association of Anatomists. She has been Editorin-Chief of the journal Developmental Biology, served on the Councils of three Institutes at the National Institutes of Health, and contributed to a long list of committees and boards. For the past 14 years she has chaired her department at Harvard Medical School. A generation of medical students at Harvard Medical School remembers her as a stimulating teacher. She has also trained a number of influential research scientists, including several former officers of this society. Betty Hay is a true triple threat: an innovative investigator, an effective administrator and citizen in the scientific community, and a successful educator. Dr. Hay is with the Department of Anatomy and Cell Biology, Harvard Medical School These remarks were made by Dr. Thomas D. Pollard, Past President of the ASCB, upon presentation of the medal.