The nerve growth factor: thirty‐five years later.

Introduction: Neurogenesis and its early experimental approach 'Embryogenesis is in some way a model system. It has always been distinguished by the exactitude even puctilio, of its anatomical descriptions. An experiment by one of the great masters of embryology could be made the text of a discourse on scientific method. But something is wrong, or has been wrong. There is no theory of development in the sense in which Mendelism is a theory that accounts for the results of breeding experiments. There has therefore been little sense of progression or timeliness about embryological research. Of many papers delivered at embryological meetings, however good they may be in themselves...one too often feels that they might have been delivered five years beforehand without making anyone much the wiser or deferred for five years without making anyone conscious of a great loss' (1). This feeling of frustration so incisively conveyed in these considerations by P.Medawar, pervaded, in the forties, the field of experimental embryology which had been enthusiastically acclaimed in the mid-thirties, when the upper lip of the amphibian blastopore brought this area of research to the forefront of the biological stage. The side branch of experimental neuroembryology, which had stemmed out from the common tree and was entirely devoted to the study of the trophic interrelations between neuronal cell populations and between these and the innervated organs and tissues was then in its initial vigorous growth phase. It in turn suffered from a sharp decrease in the enthusiasm that had inflamed the pioneers in this field, ever since R.G.Harrison delivered his celebrated lecture on this topic at the Royal Society in London in 1935 (2). Although the alternate 'wax and wane' cycles are the rule rather than the exception in all fields of human endeavor, in that of biological sciences the 'wane' is all too often indicative of a justified loss of faith in the rational and methodical approach that had at first raised so much hope. A brief account of the state-of-the-art of experimental neuroembryology in the forties, when interest in this approach to the study of the developing nervous system was waning, is a prerequisite for understanding the sudden unforeseeable turn of events which resulted in the discovery of the Nerve Growth Factor.