250 Raphael Falk
obtained through cross-breeding experiments. These principles applied when the
MendelianFaktoren—orgenes[Johannsen, 1909] — were conceived as abstract
intervening variables or as possible material-physiological hypothetical constructs
[MacCorquodale and Meehl, 1948].
The chromosomal theory of heredity introduced by Thomas Hunt Morgan and
his associates assumed that genes are discrete and distinct material unit-entities,
and Herman J. Muller set out on genetic analytic research program to determine
their physico-chemical properties (see, e.g., Muller [1922]). The nature of the
hereditary material was, however, determined by chemical raher than by genetic
analysis, and with the introduction of the Watson-Crick model of DNA structure
[Watson and Crick, 1953a] genetic analysis became molecular. “Hybridization”
was extended in prokaryotes (bacteria and viruses) beyond sexual mating, to in-
clude DNA transfer from organism to another either directly (transformation) or
through a viral vector (transduction). With the advance of genetic engineering,
sophisticated plasmids — small accessory bacterial DNA molecules, into which
foreign DNA sequences can be inserted — were constructed. These extended the
power of genetic analysis greatly, including the violation of the species-barrier of
hybridization. Such plasmids function nowadays as vectors for the hybridization
even of completely unrelated species of plants and animals. YACs (yeast artificial
chromosomes) and BACs (bacterial artificial chromosomes) are the modern vec-
tors of genetic analysis by molecular hybridization, both for the very sequencing of
DNA-segments and for the elucidation of the functional aspects of such sequences.
Furthermore, modern genetic analysis is not limited to “hybridization”in vivo.
It has been extended toin vitroanalyses, utilizing the annealing properties of
homologous sequences of polynucleotides, like that of the PCR (polymerase chain
reaction) method that amplifies specified DNA stretches (attached to primer se-
quences) by repeated cycles of dissociation of the DNA molecule and synthesis of
the complimentary homologous sequence that reanneals with the dissociated one.
Examination of homologies of nucleotide sequences by the hybridization of DNA
and RNA strands thus maintains the hallmark of genetic analysis.
*From its early steps, genetic analysis was paradigmatically reductionist. Al-
though early genetic analysis was performed almost indiscriminately with any
organism available, toward 1910 researchers converged on a relatively small num-
ber of species. By the 1930s the two major organisms for genetic and cytogenetic
research of the mechanics of hereditary transmission were the fruit flyDrosophila
melanogaster and maize (Zea mays). Experimental work was, of course also
carried out with other organisms, mammals like mice, rats, guinea-pigs; insects
like Chironomus and Sciara; and plants like Jimson weed (Datura), Snapdragon
(Antrirhinum), peas, barley etc.
In 1936 George Beadle joined Boris Ephrussi in an effort to integrate embryology
and genetics [Beadle and Ephrussi, 1936]. At the time, however, Drosophila turned
out not to be an appropriate organism to follow the developmental physiological