BY JOHN GERHART

JOHANNES HOLTFRETER WAS the world's foremost experimental embryologist in the decades between 1930 and 1960. His research was done entirely with amphibian embryos, the favored material of the time. He initiated and contributed substantially to many lines of experimentation that are still ongoing in the analysis of the embryonic organizer and of embryonic induction. For embryologists, his research shifted their view from the developing embryo as a supracellular organismal entity to the embryo as a complex population of interacting cells in which the numerous cells surrounding the organizer have a high competence for development, held in a latent state. The signals from the organizer mostly evoke or release this development, rather than provide detailed instructions for it. Our present-day concepts of secreted inductive signals, cell competence, and cellular morphogenetic activities sprang from Holtfreter's findings and insights.

Holtfreter's particular contributions include:

• The invention of Holtfreter's medium (a balanced salt solution in which operated embryos and clumps of embryonic cells survive and differentiate) and the introduction of sterile technique (1931).
• His discovery that dead and disintegrated organizer tissue could still induce locally organized parts of secondary axes (1932–38) and his findings that most tissues of embryos and adults of representative members of many animal phyla contain substances that induce neural development, findings that set off an international search for the true inducer.