On the Origin of Cancer Cells 331 



example, embryos that have been transferred from amniotic fluid to Ringer's Solu- 

 tion. Since it is always easy to detect aerobic fermentation but generally difficult 

 to detect growth, or lack thereof, of body cells, aerobic fermentation should not 

 be used as a test for cancer cells, as I made clear in 1928 1!) . 



Nevertheless, misuse is still made of aerobic fermentation. Thus, O'Connor 2 - 

 recently repeated our old experiments on the aerobic fermentation of the em- 

 bryo that has been transferred into Ringer's Solution, but he drew the conclusion 

 that the growth of normal body cells is completed at the expense of the aerobic 

 fermentation, even though it has long been established that the embryo does not 

 ferment aerobically when it grows in the amniotic fluid. 



Respiratory poisons. The specific respiration-inhibiting effect of arsenious acid 

 and the irreversibility of its inhibitions were discovered in the first quantitative 

 works on cell respiration 23 - 24 . There is abundant literature on the carcinogenesis 

 by arsenic, particularly on arsenic cancer after treatment of psoriasis and on the 

 cancer of grape owners who spray their vineyards with arsenic. The specific 

 respirationinhibiting effect of hydrogen sulfide has likewise been described by 

 Negelein 25 , and carcinogenesis by derivatives of hydrogen sulfide has been recently 

 described by D. N. Gupta 26 . 



The irreversible inhibition of cell respiration by urethane was discovered early 27 

 as well as the fact that the urethane inhibition is more irreversible the higher the 

 temperature. In sea urchin eggs, the effect of urethane was investigated, not only 

 on the metabolism, but also on cell division in studies 28 from which the later 

 urethane treatment of leukemia was developed. The physicochemical mechanism 

 by which urethane and other indifferent narcotics inhibit cell respiration was 

 cleared up in 1921 29 . Only much later did the carcinogenic effect of urethane become 

 known. Actually, multiple lung adenomas can often be produced in 100 percent 

 of the mice treated with small doses of urethane 30 . 



Oxygen deficiency. Short-period oxygen deficiency irreversibly destroys the respi- 

 ration of embryos 16 without thereby inhibiting the anaerobic fermentation of the 

 embryo. If such embryos are transplanted, teratomas are formed 31 . It has recently 

 been reported that, in the development of the Alpine Salamander, malformations 

 occurred when the respiration was inhibited by hydrocyanic acid in the early stages 

 of embryonal development 32 . 



Goldblatt and Cameron 3 reported that, in the in vitro culturing of fibroblasts, 

 tumor cells appeared when the cultures were exposed to intermittent oyxgen de- 

 ficiency for long periods, whereas, in the control cultures, no tumor cells appeared. 

 In the discussion at the Stuttgart Convention, Lettre cited against Goldblatt 

 and Cameron the fact that another American tissue culturist, Earle, has occa- 

 sionally obtained tumor cells from fibroblasts for reasons unknown to him and in 

 an unreproduceable manner, but this objection does not seem weighty, and the 

 latter part is untrue 33 . In any event, here is an area in which the methods of tissue 

 culture could prove useful for cancer research. But warnings must be given against 

 metabolism measurements in tissue cultures, if and when the tissue cultures are 

 mixtures of growing and dying cells, especially under conditions of malnutrition. 



