On Respiratory Impairment in Cancer Cells 341 



ate oxidative response shown by tumor tissue [impairment type iv; compare Kidd 

 et alß and Weinhouse ^ *■ 302 > ]. 



It is obvious that in the hands of Weinhouse the Statistical approach has led to 

 gross error in final conclusion. This erroneous conclusion has been woven into 

 his papers 4 , 5 extensively and affects still other conclusions based on it, leading to 

 general confusion not confined to his own papers 11 . 



The error concerning species adjustment that Weinhouse has introduced into 

 his consideration of "Burk's extensive tables" enters with equal force into var- 

 ious of his conclusions concerning his own experimental data 4 , 5 obtained with 

 isotopically marked Substrates, where again results with miscellaneous rat and 

 mouse materials are often mixed indiscriminately; Space, however, does not per- 

 mit tabular detailing of his propagation of errors in this direction. Suffice it to say, 

 his own data reported onOo 2 (sketchy, but republished verbatim many times) show 

 lower average species unadjusted Q02 values for the tumors ( — 5.3 for 19 deter- 

 minations) than for the normal tissues ( — 9.5 for 19 determinations) in saline- 

 substrate (nonserum) media. Unfortunately, the mouse data contain only one 

 normal tissue (liver) and several tumor types, whereas the rat data contain only 

 one tumor type (hepatoma) and several normal tissues. If more normal mouse- 

 tissue types and more rat-tumor types had been available for proper species ad- 

 justment, the adjusted values (for either species) would have been even wider apart 

 than — 5.3 and — 9.5, since the Oa> of hepatoma is relatively high among tumors 

 and the Qq 2 of normal liver tissue is relatively low among highly functional nor- 

 mal tissues. 



When, in more extensive experimentation, C 14 -marked Substrates were tested 

 (glucose, lactate, and 2,4-acetoacetate), there was in general a relatively much 

 greater aerobic production of C 14 Oo by the normal tissue groups than by the tumor 

 groups employed. On an absolute basis, <2c 14 o 2 in the tumors rarely exceeded 2 

 ("O.C." = 89), and were ordinarily well below 1 ; but normal tissues ranged up to 

 <2c 14 o 2 = ^ and more, notably with lactate, an important constituent of sera. These 

 isotope tracer studies of Weinhouse show that fatty aeids and a wide variety of 

 exogenous Substrates may be oxidized to carbon dioxide by a miscellany of rat and 

 mouse tumors, but only at quite small initial rates that were on the average lower 

 than the average of initial rates shown by the highly functional normal rat and mouse 

 tissues tested. Such studies largely confirm, albeit with superior quantitative 

 finesse, widely aeeepted conclusions reached decades ago by investigators who had 

 employed time-honored kinetic, substrate-addition, and respiratory quotient 

 methods. 



G. N. Lewis 1 ' 2 has said, "It is a common fault of mankind to refuse to recognize 

 the extence of a phenomenon unless some mechanism has been devised." Much 

 of the general confusion 11 , 13 evident in the discussion advanced by Weinhouse 

 also derives from his failure to distinguish between various over-all phenomena of 

 respiratory impairment, on the one hand, and detailed mechanisms thereof, on the 

 other. In his own experimental work he has looked for respiratory impairment 

 among details of biochemical respiratory mechanisms, following well-worn 

 Channels of possible aberrancy — for example, enzyme content 14 , citric aeid cycle, 



