Corrigenda: ultraviolet for ultraviolent!;
KW: somatic mutation theory of cancer; P-5; cf Alexander Haddow;
A Nutritional Concept of Cancer While the etiology of cancer has been
categorized under infection by a transmissible virus on the one hand
and gene mutation on the other (not to mention a host of other
hypotheses), there has been relatively little speen-
lation on the biochemical mechanisms whereby any of these
events could lead to the process recognized as neo- plastic growth.
Recent studies by Beadle, Tatum, and others, on ,the genetic control
of biosynthetic reactions in the fungus, Ne~rospora, have provided a
foundation for new concepts of the biological regulation of growth.
In particular, a study by Ryan and Lederberg (Proc. not. Acad. Sci.,
U' ash., 194fi, 32, 183-173), on the "adap- tation" of a Neurospora
mutant defieient in the syn- thesis of leueine, has provided an
experimental basis for speculative analogy with neoplasia. Field
strains of Nez~ospora will grow on medium con taining only sugar
, salts, and biotin, which is to say that the fungus is capable
of manufacturing all other essen tial metabolites. As the result
of mutations of single genes, the capacity for synthesis of various
compounds may be lost. A similar process presumably accounts for the
nutritional requirements of higher forms. Following ultraviolent treat
ment, a mutant strain of Neurospora, #33757, has been isolated which
is incapable of synthesizing leucine. As a consequence, this strain
requires leucine, and its growth is quantitatively regrr- latcd by
the available supply. Occasionally, cultures of leurineless
Ne~rospora grow11 on limiting amounts of this amino acid will "adapt";
that is, an exceptional fragment of the mycelium will grow autonomous
ly, irrespective of the available leucinc,
and may under certain conditions overgrow
the culture until the sugar is exhausted.
By genetic analysis of crosses between adapted and wild strains,
it has been shown that adaptation depends on the mutation, or
re- version, of the leucineless gene to an allele capable of
mediating the synthesis of leucine. A culture of leucineless
Neurospora has, then, two growth potentialities: a regulated
growth corresponding to the leueine externally available to it, and,
excep- tionally, autonomous growth on the basis of a gene muta-
tion leading to the synthesis of that metabolite. If one correlates
normal tissue cells with a culture of leucineless Neurosporu, both
regulated by their environ- ment, a simple analogy for cancer is
evident-the newly found capacity of a cell to synthesize an essential
metabo- lite otherwise available only in limiting and regulatory
amounts. While the Neurospora experiments suggest a muta- tional
origin for this capacity, virus infection, by pro- riding a missing
link for a blocked enzyme system, could play a corresponding role.
A consequence of this simple concept is that cancer cells may be
found to differ in their growth factor requirements from cells of
normal origin when they are grown in vitro.A Nutritional Concept
of Cancer While the etiology of cancer has been categorized under
infection by a transmissible virus on the one hand and gene mutation
on the other (not to mention a host of other hypotheses), there has
been relatively little speen- lation on the biochemical mechanisms
whereby any of these events could lead to the process recognized as
neo- plastic growth. Recent studies by Beadle, Tatum, and others,
on ,the genetic control of biosynthetic reactions in the fungus,
Ne~rospora, have provided a foundation for new concepts of the
biological regulation of growth. In particular, a study by Ryan
and Lederberg (Proc. not. Acad. Sci., U' ash., 194fi, 32, 183-173),
on the "adap- tation" of a Neurospora mutant defieient in the syn-
thesis of leueine, has provided an experimental basis for
speculative analogy with neoplasia. Field strains of Nez~ospora
will grow on medium con taining only sugar, salts, and biotin,
which is to say that the fungus is capable of manufacturing all
other essen tial metabolites. As the result of mutations of single
genes, the capacity for synthesis of various compounds may be lost
. A similar process presumably accounts for the nutritional
requirements of higher forms. Following ultraviolent treatment,
a mutant strain of Neurospora, #33757, has been isolated which
is incapable of synthesizing leucine. As a consequence, this
strain requires leucine, and its growth is quantitatively
regrr- latcd by the available supply. Occasionally, cultures
of leurineless Ne~rospora grow11 on limiting amounts of this
amino acid will "adapt"; that is, an exceptional fragment of
the mycelium will grow autonomously, irrespective of the available
leucinc, and may under certain conditions overgrow the culture until
the sugar is exhausted. By genetic analysis of crosses between
adapted and wild strains, it has been shown that adaptation depends
on the mutation, or re- version, of the leucineless gene to an allele capable of mediating the synthesis of leucine. A culture of leucineless Neurospora has, then, two growth potentialities: a regulated growth corresponding to the leueine externally available to it, and, excep- tionally, autonomous growth on the basis of a gene muta- tion leading to the synthesis of that metabolite. If one correlates normal tissue cells with a culture of leucineless Neurosporu, both regulated by their environ- ment, a simple analogy for cancer is evident-the newly found capacity of a cell to synthesize an essential metabo- lite otherwise available only in limiting and regulatory amounts. While the Neurospora experiments suggest a muta- tional origin for this capacity, virus infection, by pro- riding a missing link for a blocked enzyme system, could play a corresponding role. A consequence of this simple concept is that cancer cells may be found to differ in their growth factor requirements from cells of normal origin when they are grown in vitro.A Nutritional Concept of Cancer
While the etiology of cancer has been categorized under
infection by a transmissible virus on the one hand and
gene mutation on the other (not to mention a host of
other hypotheses), there has been relatively little speen-
lation on the biochemical mechanisms whereby any of
these events could lead to the process recognized as neo-
plastic growth. Recent studies by Beadle, Tatum, and
others, on ,the genetic control of biosynthetic reactions
in the fungus, Ne~rospora, have provided a foundation
for new concepts of the biological regulation of growth.
In particular, a study by Ryan and Lederberg (Proc.
not. Acad. Sci., U' ash., 194fi, 32, 183-173), on the "adap-
tation" of a Neurospora mutant defieient in the syn-
thesis of leueine, has provided an experimental basis for
speculative analogy with neoplasia.
Field strains of Nez~ospora will grow on medium con
taining only sugar, salts, and biotin, which is to say that
the fungus is capable of manufacturing all other essen
tial metabolites. As the result of mutations of single
genes, the capacity for synthesis of various compounds
may be lost. A similar process presumably accounts for
the nutritional requirements of higher forms.
Following ultraviolent treatment, a mutant strain of
Neurospora, #33757, has been isolated which is incapable
of synthesizing leucine. As a consequence, this strain
requires leucine, and its growth is quantitatively regrr-
latcd by the available supply.
Occasionally, cultures of leurineless Ne~rospora grow11
on limiting amounts of this amino acid will "adapt";
that is, an exceptional fragment of the mycelium will
grow autonomously, irrespective of the available leucinc,
and may under certain conditions overgrow the culture
until the sugar is exhausted. By genetic analysis of
crosses between adapted and wild strains, it has been
shown that adaptation depends on the mutation, or re-
version, of the leucineless gene to an allele capable of
mediating the synthesis of leucine.
A culture of leucineless Neurospora has, then, two
growth potentialities: a regulated growth corresponding
to the leueine externally available to it, and, excep-
tionally, autonomous growth on the basis of a gene muta-
tion leading to the synthesis of that metabolite.
If one correlates normal tissue cells with a culture of
leucineless Neurosporu, both regulated by their environ-
ment, a simple analogy for cancer is evident-the newly
found capacity of a cell to synthesize an essential metabo-
lite otherwise available only in limiting and regulatory
amounts.
While the Neurospora experiments suggest a muta-
tional origin for this capacity, virus infection, by pro-
riding a missing link for a blocked enzyme system, could
play a corresponding role. A consequence of this simple
concept is that cancer cells may be found to differ in
their growth factor requirements from cells of normal
origin when they are grown in vitro.
More:
jl 12/18/99
"A Nutritional Concept of Cancer" [with a letter from Joshua Lederberg to Jan Sapp] (October 25, 1991)