858 



SCIENCE 



[N. S. Vol. XL. No. 1041 



and witli the organism as a whole, than 

 does the normal tissue cell (or, as an 

 alternative assumption, there may be in 

 the nucleus special division-forcing or di- 

 vision-preventing chromosomes) ; fifth, a 

 malignant cancer cell is one having an ab- 

 normal chromosome complex v^hich continu- 

 ally reacts to a division stimulus from the 

 surroundings, or in which the division-prevent- 

 ing chromosomes are absent, or in which 

 possible division-forcing chromosomes are 

 present in multiple number; sixth, the ma- 

 lignant tumor always arises from one single 

 cell; seventh, this primordial cancer cell 

 arises by abnormal division of an otherwise 

 normal tissue cell and may start from any one 

 of a large number of different causes. 



Of these assumptions the first, second and 

 third are supported by experimental evidence; 

 the fourth may be accepted as a corollary from 

 the experimental evidence. The remainder, 

 while based upon the experimental evidence, 

 are not supported by direct evidence. 



The experimental evidence is based upon 

 the well-known work by Boveri himself on 

 dispermic eggs of the sea-urchin in which, 

 through multipolar spindles, the chromosomes 

 are irregularly distributed in the four result- 

 ing cells. Such four-cell stages, submitted to 

 the action of Herbst's decalcified sea water, 

 separate and develop on immersion in normal 

 sea water. The variety of irregular and ab- 

 normal larvse resulting from this treatment 

 indicate the qualitative differences of the 

 chromosomes and the need of a balanced 

 chromosome complex. Further experimental 

 evidence of the qualitative difference of 

 chromosomes is furnished by the modern work 

 in cytology and in experimental breeding, 

 especially in connection with the sex chromo- 

 some. Observations and experiment have led 

 to the general acceptance of the theory of the 

 individuality of the chromosomes and of the 

 conclusion that a chromosome, once lost, can 

 not be replaced or regenerated from other 

 chromosomes. 



That single chromosomes of tissue cells of 

 vertebrates represent different activities in 

 the cell is the basic assumption in Boveri's 



cancer theory. In his earlier experimental 

 work he showed that some chromosomes 

 might be absent without causing ill effects on 

 the further activity of the cell, while the loss 

 of others would be shown by pathological ef- 

 fects on future structures and activities. K 

 the same principle holds for tissue cells, an 

 abnormal mitosis might give rise to cells with 

 an unequal distribution of chromosomes, and 

 such cells might have a chromosome complex 

 which would permit the ordinary, controlled 

 activities of the cells of that particular tissue, 

 and the result would be relatively harmless; 

 or, one of such cells might have an abnormal 

 chromosome complex in which the controlling 

 factors of division are either absent or over- 

 balanced and unlimited growth and division 

 would result. Not every abnormal mitosis in 

 normal tissue cells would thus lead to tumor 

 formation but only such as have the abnormal 

 chromosome complex which represents an 

 uncontrolled growth and division energy. His 

 theory thus demands that a given cancer 

 arises from one original cancer-producing cell 

 which transmits its chromosome complex and 

 its abnormal peculiarities to all of its 

 daughter cells and so gives to the cancer, as- 

 a whole, its peculiar cellular characteristics. 

 The theory has nothing to do with abnormal 

 mitoses in the cancer cells themselves; such 

 abnormal mitoses tend to break up the pe- 

 culiar and malignant chromosome complex and 

 to render the progeny of such cells harmless.. 

 In a sense therefore, abnormal mitoses in can- 

 cer might be indicative of spontaneous heal- 

 ing, although by the theory it is equally pos- 

 sible that a new and more malignant type of 

 cancer might be started. 



The cause of a malignant tumor, according^ 

 to this hypothesis, thus may be anything 

 which induces abnormal mitoses; for example, 

 chronic irritation sets up regenerative proc- 

 esses and continues to act during the mitotic 

 processes involved in this regeneration. One 

 or several mitotic figures might be broken up- 

 by such irritation thus giving rise to unequal 

 distribution of chromosomes in the resulting 

 cells, some or one of which might have the 

 chromosome complex necessary for continued 



