Genetic Analysis 251or biochemical metabolic problems. Thus, Beadle joined Edward Tatum in the
study of a simpler organism, the moldNeurospora crassa. Neurospora turned
out to be not only extremely well adapted to the research of genetic control of
metabolic pathways, it also significantly extended the power of genetic analysis of
the mechanisms of inheritance.
In the 1940s Salvador E. Luria and Max Delbr ̈uck [Luria and Delbr ̈uck 1943]
and Joshua Lederberg and Tatum [1946] went still further and showed that ge-
netic analysis of bacteria was feasible. Thus, by the time Watson and Crick put
forward their model of DNA structure [Watson and Crick, 1953b], genetic analy-
sis of prokaryotes, mainlyEscherichia coliandSalmonella typhimuriumand their
viruses (bacteriohages) was well advanced to accommodate the era of molecular
genetics.
The peak of genetic research as a paradigmatic reductionist science, was attained
with Crick’s “Central Dogma” [Crick, 1958] of the role of genes as the one-way
providers of information at the functional-molecular level, and with Dawkins’ “self-
ish genes” [Dawkins, 1976] as the determinants of fitness in Darwinian evolution.
However, turning the focus of molecular genetics back to eukaryotes in the 1960s
soon revealed the inadequacy of the rductionist program of molecular biologists.
As noted by Sydney Brenner, the paradigm of gene regulation “does not tell us
how to make a mouse but only how to make a switch” [Brenneret al., 1990]. The
need to consider the impact of both ontogenetic and phylogenetic organizational
constraints, increasingly forced molecular genetic analysis of the end of the twen-
tieth century, to overcome the functional analyses of single genes for a top-down
systems’ analysis of ‘developmental-biology’, as well as to evolution.
Genes were no more discrete, unreducible entities [Beurtonet al., 2000]. And,
besides the time-honored mouse and Drosophila, new organisms such as yeast
(Saccharomyces cerevisiae), the nematodeCaenorhabditis elegans, and the plant
Arabidopsis thaliana, were added as experimental model organisms. Toward the
end of the twentieth century and the Human Genome Project, humans too, or at
least their DNA sequences, were added to the list of model organisms.
In what follows I wish to present the history of genetic analysis as the history
of an internally consistent and continuously unfolding conceptual methodology of
hybridization.
2 FROM FACTORS TO GENES: MENDEL TO JOHANNSENThe nineteenth century, a period of great advances in the life-sciences, was inflicted
with tensions between the introduction of reductionist notions and methodologies
according to the model of the physical sciences, and the traditional vitalist and
organismic beliefs in the existence of special laws of nature concerning living forms.
Of the three great material theories of the life-sciences in the nineteenth century,
Darwin’s theory of evolution by natural selection, Schwann and Schleiden’s cellular
theory that culminated in Virchow’s maximomni cellule e cellula, and Mendel’s
theory of heredity by discrete factors, Mendel’s was the most explicit reductionist