342 On Respiratory Impairment in Cancer Cells 



exogenous Substrate Oxydation, localized "bottlenecks" in electron transport, 

 pyruvate shunt, hexosemonophosphate shunt, and fluoride and dinitrophenol 

 inhibitions. The results obtained by him, even with isotopic tracers, have in no 

 way contra-indicated the over-all phenomena of respiratory impairment, and have 

 indeed provided some valuable supporting evidence. In any event, such conven- 

 tional and assuredly worthwhile studies are, regardless of outcome, no more essen- 

 tial to experimental recognition of the overall phenomena of respiratory impair- 

 ment in living Cancer cells than is knowledge of the ultimate physical mechanism 

 of gravitation essential to experimental recognition of the Square law of gravitation. 

 In the words of Isaac Newton 15 , "the main Business of Natural Philosophy is to 

 argue from Phaenomena . . . we must learn from the Phaenomena of Nature what 

 are the Laws and Properties of the Attraction before we enquire the Cause by which 

 the Attraction is perform'd." 



It is a tribute to the genius of Otto Warburg that he discovered the impaired 

 <2o 2 of Cancers more than 30 years ago with the now absolete methods and relatively 

 poor (mixed) Cancer materials then available, and under the handicap of the 

 Statistical approach. It is a further tribute that in recent years Warburg has been 

 the first to appreciate and capitalize on the importance of the use of pure Cancer 

 cells (for example, ascites and tissue culture cells) for final decision on the relative 

 Status of Qo 2 in Cancer cells. It should never be forgotten, however, that in the 

 characterization of Cancer metabolism, once developed following carcinogenesis, 

 he has always (1924 — 1956) regarded the invariably high ratio of fermentation to 

 respiration (impairment type i) as of much greater significance than the usually 

 low<2<)2 (impairment type ii). 



On the basis of impairment type i, and as a confirmatory qualitative demon- 

 stration thereof, the following simple manometric test has been devised 16 that per- 

 mits investigators to distinguish Cancer cells from virtually all normal body cells, 

 growing or nongrowing. The cells under test are placed in a manometric vessel of 

 any convenient size. The vessel is filled to one-third to one-half of its volume with 

 physiological serum or other equivalent body fluid (5 percent CO-2 in O2 or air as 

 appropriate, slight alkalinity, adequate glucose and bicarbonate). The volume of 

 cells is of the order of 1/300 the volume of serum. Cancer cells cause the mano- 

 meter to register a steady and notable increase in pressure with time (minutes to 

 hours), whereas normal (uninjured) body cells cause a negative (or <~ zero) change 

 in pressure with time. The few — if any — exceptions extant are only apparent, or 

 are readily ruled out on other bases ; thus, use of nonphysiological media (for ex- 

 ample, unfortified saline) may vitiate the test for normal cells, and Omission of the 

 carbohydrate glucose certainly will for Cancer cells. 



This test can be made quantitative, but in the simple form just outlined it pos- 

 sesses the advantage of being qualitative. It offers a distinction between neoplastic 

 and normal cells that is as qualitative as "plus versus minus" or "up versus down," 

 and that is observable in terms of mere pressure change — that is, directional 

 movement of the manometric fluid. The quantitative metabolic basis for the ob- 

 served qualitative manometry is completely understood. Thus, the sign and magni- 

 tude of the pressure change can be expressed as an exact mathematical function of 



