A Critique of Pure (Genetic) Information

144 Chapter 4
chromosomes provided the opportunity to identify the particular chromosomes
required for suppressing a malignant phenotype. Where the
spontaneous loss of a certain chromosome correlated with the expression
of the malignant phenotype, it was surmised that that chromosome,
when present, suppressed that malignant phenotype. Mouse chromosome
4, for example, was found to be responsible for suppressing a wide
range of tumor cells including those expressing retroviral oncogenes
(Harris 1988). Human chromosome 1, which was shown to have significant
homology with mouse chromosome 4, was likewise seen to be
capable of suppressing a wide range of human tumor cell phenotypes.
Studies on human chromosome 11 found it to be associated with the
suppression of malignancy in fusion experiments consisting of human
uterine carcinoma and a normal human fibroblast (Harris 1988). Further
technical advances enabled researchers to demonstrate directly that
single copies of chromosome 11, when delivered by the new method of
microcell transfer, were able to suppress the malignant phenotype of
either uterine carcinoma or of Wilms tumor cells (Harris 1988). Similar
methods localized putative tumor suppresser capabilities to nine different
chromosomes (Levine 1993). A next step in the logic of this research
program was to locate and identify the specific tumor suppressor genes
situated on these chromosomes.
Somatic cell hybridization studies were one source of the tumor suppressor
gene model; epidemiological studies on the childhood cancer
retinoblastoma was another. Retinoblastoma arises from cells of the
embryonal neural retina and occurs only in young children. In most
cases, retinoblastoma arises sporadically (not along family lines) with
an incidence of approximately 1:20,000, yet in about one-third of
cases overall the tumor did appear to follow some heritable pattern
(Stanbridge 1990). A. J. Knudson in 1971 proposed a “two-hit” model
in order to account for this split between heritable and sporadic forms
of the cancer. Consistent with the idea of a recessive pattern, Knudson
suggested that the same locus was involved in both sporadic and familial
forms of the disease but that in the familial form one of the alleles
was already mutated in the germ line. A single somatic mutation involving
the homologous locus in the unaffected chromosome would then be
enough to generate the tumor in the predisposed individual, whereas in
sporadic retinoblastoma two mutations must occur somatically in the