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The Joshua Lederberg Papers

Title:
A Nutritional Concept of Cancer Annotation pdf (137,188 Bytes) ocr (3,265 Bytes)
A Nutritional Concept of Cancer
Number of Image Pages:
2 (137,188 Bytes)
Date:
1946-11-01 (November 1, 1946)
Creator:
Lederberg, Joshua
Source:
Periodical: Lederberg, Joshua. "A Nutritional Concept of Cancer." Science 104, 2705 (1 November 1946): 428. Article. 2 Images.
Lederberg UI: P5
Publisher:
American Association for the Advancement of Science
Rights:
Reproduced with permission from the American Association for the Advancement of Science. Readers may view, browse, and/or download this material for temporary copying purposes only, provided these uses are for noncommercial personal purposes. Except as provided by law, this material may not be further reproduced, distributed, transmitted, modified, adapted, performed, displayed, published, or sold in whole or in part, without prior written permission from AAAS.
Subject:
Medical Subject Headings (MeSH):
Mutation
Neoplasms
Nutritional Physiological Phenomena
Relation:
Lederberg Grouping: Published Scientific Article
Metadata Record "A Nutritional Concept of Cancer" [with a letter from Joshua Lederberg to Jan Sapp] (October 25, 1991) pdf (94,440 Bytes)
/ps/access/BBGMSJ.pdf
Metadata Record "A Nutritional Concept of Cancer" [with Lederberg's 1982 handwritten annotations] [1946, 21 November 1982] pdf (100,908 Bytes)
/ps/access/BBGMSK.pdf
Metadata Record "A Nutritional Concept of Cancer" [with a letter from Joshua Lederberg to James F. Crow] (February 20, 1994) pdf (108,779 Bytes)
/ps/access/BBGMSL.pdf
Metadata Record "A Nutritional Concept of Cancer" [with a letter from Joshua Lederberg to Alvin M. Weinberg, Oak Ridge National Laboratory] (1968) pdf (90,095 Bytes)
/ps/access/BBGMSM.pdf
Box Number: 79
Folder Number: 7
Unique Identifier:
BBABEO
Accession Number:
3
Document Type:
Articles
Language:
English
Format:
application/pdf
image/tif
Physical Condition:
Good
Series: Writings
SubSeries: Published Scientific Articles
Folder: P5: "A Nutritional Concept of Cancer" (1946)
Metadata Last Modified Date:
2006-03-06
Linked Data:
RDF/XML     JSON     JSON-LD     N3/Turtle     N-Triples

Annotation by Joshua Lederberg:

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.


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