Title:

A Nutritional Concept of Cancer

Creator:

Lederberg, Joshua

Date:

1 November 1946

Periodical:

Science

Publisher:

American Association for the Advancement of Science

Location:

Box: 79. Folder: 7

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.

Genre:

Articles

Subject:

Mutation, Neoplasms, and Nutritional Physiological Phenomena

Format:

Text

Extent:

2 pages

Relation:

A Nutritional Concept of Cancer [with a letter from Joshua Lederberg to Jan Sapp], 1991
A Nutritional Concept of Cancer [with Lederberg's 1982 handwritten annotations], 1946
A Nutritional Concept of Cancer [with a letter from Joshua Lederberg to James F. Crow], 1994
A Nutritional Concept of Cancer [with a letter from Joshua Lederberg to Alvin M. Weinberg, Oak Ridge National Laboratory], 1968

Language:

English

Legacy Source Citation:

Periodical. Lederberg, Joshua. "A Nutritional Concept of Cancer." Science 104, 2705 (1 November 1946): 428. Article. 2 Images.. Science. Lederberg UI. P5

Legacy ID:

BBABEO

NLM ID:

101584906X771

Profiles Collection:

The Joshua Lederberg Papers

Shareable Link:

https://profiles.nlm.nih.gov/101584906X771

Annotation:

Author: Joshua Lederberg. Date Written: December 19, 1999. 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

Lederberg Grouping:

P. Published Scientific Article.