276 Raphael Falk
could be mapped into consistent linear sequences [Pontecorvo, 1958]. The genes
turned out to be complex, linear structures, more like “molecules” than “atoms”
of inheritance.
These results obtained new significance once Watson and Crick presented their
model for the genetic material, the double stranded DNA molecule of complimen-
tarily paired nucleotides, adenine with thymine and guanine with cytosine. Muller
accepted that “modern evidence supports the conception of a linear arrangement of
the genetic material all the way down to its ultimate components, the nucleotides”,
and “we arrive at a conclusion in harmony with the model that has been presented
to us by Watson and Crick” [Muller, 1956]. But he continued to argue for “the case
for a segmented chromosome” of discrete and distinct genes, on both experimental
— most chromosome breaks are between genes — and theoretical grounds:
Our best evidence for intragenic mutation... consists of the evidence
in all its great sweep and diversity for the theory of evolution itself,
taken in conjunction with the evidence for the existence of individ-
ual genes. So long as we retain both concepts we must admit that at
the bottom evolution has been built up out of intragenic mutations,
together with some superstructure of intergenic structural changes.
[Muller, 1956, 134]As Watson and Crick [1953a] suggested, “many lines of evidence indicate that
[DNA] is the carrier of... the genetic specificity of the chromosomes and thus of
the gene itself”. Yet, in spite of its elegance, the Watson and Crick model posed
some serious problems. Primary among those was that raised by Max Delbr ̈uck,
of the difficulties in unwinding of long coils of the double helix toward replication
and the rewinding of the replicated product (see Holmes [2001]; Kay [2000]). The
experimental evidence for the semi-conservative replication of DNA, each double
helix of the newly replicated DNA consisting of one helix of the parental double
helix, and one newly synthesized [Meselson and Stahl, 1958] — extending the
methodology of hybridization to the molecular level – only amplified claims that
the chromosomes must be composed of many DNA molecules each unwinding,
replicating and rewinding independently, as was implicit in Muller’s argument for
separate, discrete genes along the chromosomes. At the time Stahl [1961] even
suggested that the chromosomes were composed of chains of DNA molecules, each
being circular (and containing several genes). However, as noted (see sections 3
and 3.1), the continuity of the DNA molecule of both the bacterial chromosome
and that of the eukaryotic chromosomes was eventually established.
The reservations of his mentor Max Delbr ̈uck notwithstanding, the new con-
ception of the gene as a stretch of DNA prompted Seymour Benzer to map a gene
of the bacteriophage T4, “down to the ground” [Holmes, 2000]. rIImutants are
transnon-complimentary in double infection and do not multiply in the ofE. coli
strain K12(λ) bacteria (whereas they multiply normally inE. colistrain S and
asroughplaques onE. colistrain B). Benzer screened mutants belonging to the
same complementation unit for “any wild-type recombinants which arise, even in