April 15, 1921] 



SCIENCE 



355 



which certain reactions take place. Thus in 

 the series of reactions 



if the rate of O — > S becomes slower than 

 the normal, injury will occur, while a return 

 to the normal rate will result in recovery. 

 Injury could also be produced by increasing 

 the rate of M — > B, or decreasing ihe rate of 

 S^A or A-^M. 



If life is dependent upon a series of re- 

 actions which normally proceed at rates bear- 

 ing a definite relation to each other, it is 

 clear that a disturbance of these rate-rela- 

 tions may have profound effects upon the 

 organism, and may produce such diverse 

 phenomena as stimulation, development, in- 

 jury and death. It is evident that such a 

 disturbance might be produced by changes 

 of temperature (in case the temperature 

 coefficients of the reactions differ) or by 

 chemical agents. The same result might be 

 brought about by physical means, especially 

 where structural changes occur which alter 

 the permeability of the plasma membrane or 

 of internal structures (such as the nucleus 

 and plastids) in such a way as to bring to- 

 gether substances which do not normally 

 interact. 



In the case of Laminaria death may occur 

 in two ways. In the first there is a loss of 

 resistance which continues until the death 

 point is reached, as, for example, in sodium 

 chloride. In the second, as in calcium 

 chloride, there is an increase of resistance 

 followed by a decrease. Both of these meth- 

 ods may be predicted by means of the scheme 

 already outlined. 



If we mix sodium chloride with calcium 

 chloride we do not get a result which is 

 merely intermediate for we find that long 

 after death has occurred in pure sodium 

 chloride or pure calcium chloride the tissue 

 still survives in a mixture of these salts 

 (made in certain definite proportions). The 

 facts lead us to assume that both sodium and 

 calcium combine with a • constituent, X, of 

 the protoplasm, forming a compound Na^XCa. 

 According to the laws of mass action we may 



calculate the amount of this compound which 

 will be formed in each mixture of sodium 

 and calcium chlorides. These calculations 

 indicate that the speed of all the reactions 

 is regulated by the amount of IsTa^XOa (it is 

 also found that certain reactions are acceler- 

 ated by calcium chloride). 



This enables us, by means of the equations 

 already mentioned, to predict the time curves 

 of injury and death in mixtures (in addition 

 to those in pure salts) as well as the recovery 

 curves when tissue is transferred from such 

 mixtures to sea water. 



It is evident therefore that the theory not 

 only explains why pure sodium chloride and 

 calcium chloride are toxic but also why they 

 antagonize each other in mixtures. More- 

 over the explanation which it furnishes is a 

 quantitative one, i.e., it shows just what de- 

 gree of antagonism is to be expected in each 

 mixture. 



Extremely interesting results are obtained 

 when the tissue is first exposed to sodium 

 chloride, then to calcium chloride, then to 

 sodium chloride or to sea water and so on. 

 By varying the conditions of the experiment a 

 very complicated set of curves may be ob- 

 tained. It is rather remarkable to find that 

 all of these may be predicted with consider- 

 able accuracy by means of the equations 

 already referred to. A detailed statement of 

 the results will be found in recent papers in 

 the Journal of General Physiology. 



Throughout these investigations the aim 

 has been to apply to the study of living 

 matter the methods which have proved useful 

 in physics and chemistry. The attempt pre- 

 sented no serious difficulties after accurate 

 methods of measurement had been devised: 

 nor does there seem to be any real obstacle 

 to a general use of methods which lead 

 biology in the direction of the exact sciences. 



It is evident that if the facts have been 

 correctly stated such fundamental conceptions 

 as vitality, injury, recovery and death may be 

 investigated by quantitative methods. This 

 leads us to a quantitative theory of these phe- 

 nomena and a set of equations by which they 

 can be predicted. It may be added that the 



