286 Raphael Falk
with both Drosophila, and the mothEphestia kuhnellia performed by K ̈uhn, it
turned out that the systems were too complex for such detailed reductive anal-
ysis. Although some embryological and biochemical analysis was further carried
out along these lines [Rheinberger, 2000a], Beadle was prompted to look for more
basic systems, where it would be possible to establish the effects of single gene.
His collaboration with Tatum on the metabolic pathways in the moldNeurospora
crassaculminated in the reductionist concept of “one gene — one enzyme”, that
proved to be a productive analysis not only for the elucidation of the function of
specific genes, but alsovice versa, for establishing yet unknown steps in metabolic
pathways [Beadle, 1945; Beadle and Tatum, 1941a, 1941b], (see also Schwartz
[1998]).
Already in 1929 Sturtevant realized that genetic markers could be extremely
helpful tools in developmental analysis. Aclareteye-color mutant ofDrosophila
simulansproved to induce frequent X-chromosome non-disjunction in early cleav-
age divisions of the embryo, producing gynandromorphic flies, half of their body
being XO, i.e., male, and half being XX, i.e., female [Sturtevant, 1929]. Marking
one of the X-chromosomes with a recessive marker likeyellowproduced gynan-
dromorphs in which male parts were marked yellow. Since the demarcation line
between the female and male parts varied from one case to another, Sturtevant
concluded that the nuclei at the early cleavage divisions were still non-determinate
with respect to organ differentiation. Furthermore, using the X-chromosome linked
vermillioneye color mutant, he found it to be non-autonomous; even when one
eye was male and the other female according to theyellowmarker, both eyes were
either vermillion or wild type, according to the genotype of a region of the thorax
(which turned out to be the ring-gland). Sturtevant thus made an early genetic
analysis fate-mapping of the “focus” of the vermillion eye color of Drosophila.
Genetic analysis of the developmental roles of various specific genes was applied
in different organisms. In maize, mutations occurring with abnormally high fre-
quency in genes that affect the development of the seeds’ pericarp pigmentation
[Emerson, 1914] culminated in McClintock’s model of regulatory genes “jumping”
to different chromosome sites due to breakage and rejoining cycles [McClintock,
1951]. In the rat the pleiotropic effects on complex phenotype of specific genes was
studied by Gruneberg [1938], whereas Glueckson-Waelsch’s studies of the embry-
ological effects of single mutations elucidated interactions of basic induction pro-
cesses in skeleton and urogenital differentiation in the mouse [Gilbert, 1991]. Curt
Stern utilized the phenomenon of mitotic crossing-over, inducible by mild doses
of X-rays in Drosophila, that yielded in heterozygotes for genetic markers (like
yellowandsinged) somatically marked cell “spots” homozygous for the markers,
and thus detectable on the background, to follow the site-determination of bristle
development in the flies [Stern, 1955]. However, the most systematic embryolog-
ical research project was that of the genetic control of the developmental course
of lethal mutations at specific genes in Drosophila flies [Hadorn, 1961]. Ernst
Hadorn and his students studied, among others, the constancy of the developmen-
tal fate of imaginal discs of Drosophila: Imaginal discs from larvae were cultured