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Reprinted from Science, November 1, 1946, Vol. 104, No, 2705, | page 428.

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 specu-
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, Neurospora, have provided a foundation’
‘for new concepts of the biological regulation of growth.
In. particular, a ‘study: by: Ryan. and Lederberg | (Proce
“nat: Acad. Sci.; Wash., 1946, 32; 163-173), on the ‘‘adap- ~

tation’? “of a "Neurospora. mutant deficient’ in the syn-
thesis of leucine, has provided an experimental basis for
" speculative analogy with neoplasia.

Field strains of Neurospora will grow on medium con-

taining only sugar, salts, and biotin, which is to say that.

the fungus is capable of mantfacturing 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 ultravidlent treatment, a mutant ‘strain of
om eurospora, #33757, has been isolated which i is incapable’.
Asa “consequence, this: strain ~

“of “synthesizing leucine.
“requires leucine, and its growth. is quantitatively regu-
“lated by the available’ supply.

 Oceasionally,” cultures of leucineless Né eurospora grown

on limiting amounts of this amino acid will ‘‘adapt??; -

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_Yiding a missing link for a blocked enzymes

_ play a corresponding role.
concept | is that cancer. cells may be- found . to. differ, ins: .
. their” ‘growth ‘factor ‘requirements: from’ cells - ‘of: ‘normal
“origin when they are grown in vitro,

 

that is, an exceptional fragment of the mycelium. will’

grow autonomously, irrespective of the available leucine,
and may under certain conditions overgrow the. culture’.
until. the sugar is exhausted. By’ genetic analysis of

” erosses 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--eulture of leucineless Neurospora. has, then, two’
growth patentialities: a regulated growth corresponding .
to the leucine. externally ; available -to it, and, . excep-,

: tionally, autonomous growth « on ‘the basis of a gene” “muta: ©
: tion leading ‘to the syn hesis of. that metabolite.

If one: correlates normal’ tissue “eels with. a culture’ of |:
leucineless Neurospora, 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
tional origin for this capacity.

   
  
    
   

“A consequence of this simple .

.. JOSHUA LEDERBERG
Osborn Botanical Laboratory, Yale University, and
College of Physicians and Surgeons, Columbia University

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