During the purification of nerve growth factor from mouse submaxillary glands by carboxymethyl cellulose chromatography, distinct biological activities were noticed when a fraction that did not contain nerve growth promoting activity was injected into newborn mice (Cohen 1960; Levi-Montalcini and Cohen 1960). These new responses included precocious opening of the eyelids, eruption of incisors, an inhibition of hair growth, and “stunting” of growth. Two years later Cohen (1962) reported the isolation of a heat-stable protein from mouse submaxillary glands, termed “tooth-lid factor”, which reproduced the developmental effects on the eyelids and incisors. Histological studies indicated that the precocious eyelid opening in “factor-treated” animals was the consequence of a generalized increase in epidermal thickening and keratinization (Cohen and Elliott 1963). When studies performed in vitro with explants of either skin or epidermis demonstrated a direct effect on epidermal growth, the tooth-lid factor was termed epidermal growth factor or EGF (Cohen 1964).