What history tells us XII. Boris Ephrussi’s continuing efforts to create a “genetics of differentiation”

Abstract

Students in biology know that the work of Boris Ephrussi and George Beadle on the genetic control of eye pigmentation in Drosophila was the first step towards the establishment, a few years later, of the "one gene-one enzyme" relationship by George Beadle and Edward Tatum through their work on fungus Neurospora. After the Second World War, Ephrussi's discovery of the petite mutations that blocked respiration in yeast, and the demonstration of the cytoplasmic inheritance of these mutations, were decisive steps in the development of mitochondrial genetics in the 1960s. Less well known is the equally important role that he played in the development of cell hybridization and somatic cell genetics at the beginning of the 1960s. This development took place simultaneously with the establishment of cell lines derived from teratocarcinomas. Ephrussi's demonstration of the potential of these cell lines for the study of differentiation was exploited later by Francois Jacob and amply confirmed since by numerous studies of embryonic stem cells (Morange 2006). The plurality of the projects pursued by Ephrussi during his life has been considered as a dispersion of efforts and as an indication of the difficulties encountered by those who, like him and Waddington, tried to reconcile embryology and genetics. Ephrussi famously said of Thomas Hunt Morgan's 1934 book Embryology and Genetics that it was the sum of knowledge accumulated in genetics and embryology, not the expected linking together of these two disciplines. My aim in this article is not to sketch a complete scientific biography of Ephrussi - excellent contributions have already been made in this direction (Roman 1980; Sapp 1987; Burian et al 1988, 1991; Burian and Gayon 1990, 1999) -, but to outline characteristics of his early contributions as well as to emphasise the importance of the later ones, which so far have not received the attention they deserve (with the exception of Weiss 1992; Zallen and Burian 1992). Focussing on his last studies is also a way to underline the profound unity of Boris Ephrussi's work: some of the questions he raised are still at the core of biologists' investigations.