354 General Discussion 



cellular compartments for ATP, inorganic phosphate, DPN, TPN, 

 enzymes, substrates, and so on. 



Krehs : It has been suggested that we might discuss the use of the 

 term "feedback". The word feedback comes originally from purely 

 physical systems. The German term is "Riickkopplung". It 

 originated in the 1930's in the field of electronics and is used for many 

 physical devices. If we use it for chemical systems we extend the 

 use of the term, but we all know what we mean. The essence of 

 feedback is that the process, as it progresses, creates conditions 

 which are unfavourable for the further progress of the process and 

 cause it to stop. This stoppage in turn leads to environmental 

 changes, because we are dealing with a system which is in equili- 

 brium — and that is a fundamental issue — but a system in a steady 

 state where various processes happen continuously. Therefore, the 

 stoppage of any particular process would automatically lead to 

 further changes which again favour the particular process and make 

 it go on faster. One of the simplest feedback devices is a thermo- 

 regulator, fed by gas. A device is incorporated in the gas supply 

 (an expanding fluid) which cuts off the gas supply by the effect of 

 the gas, i.e. heat. 



Magasanik: Is that what one would call, strictly speaking, 

 negative feedback? 



Krehs: Yes. Engineers speak of negative feedback when an 

 increased output decreases the input, and of positive feedback 

 when an increased output increases the input. Thus, the inhibition 

 of pyrimidine synthesis by cytidylic acid is negative feedback. On 

 the other hand, the stimulation of respiration by ADP and/or 

 phosphate may be looked upon as positive feedback : in this case the 

 greater the rate of ATP utilization, i.e. the rate of formation of ADP 

 and phosphate, the greater becomes the rate of respiration and oxida- 

 tive phosphorylation. I feel that it is generally unnecessary, in the 

 chemical systems which we are considering, to mention the "sign" 

 of the feedback mechanism. (For further reference, see Tustin, A. 

 (1953). The Mechanism of Economic Systems. London: Heine- 

 mann; Flanagan, D., and Svirsky, L. Eds. (1957). Automatic 

 Control, Sci. Amer. London: Bell.) 



Chance: A simple diagram (Fig. lA) should help to explain what 

 negative feedback may signify to workers in the field of electronic 

 circuitry. The input to the electrical system, designated Ejn, causes 

 a flow of electrons along the input conductor. These electrons then 

 flow into another conductor at a potential — Eout- The amplifier 

 provides a potential Eout of such magnitude that the electron flow 

 through R2 is exactly equal to the electron flow through Rj. If 

 these electron flows should be unequal, the ampHfier would adjust 



