450 



SCIENCE 



[N. S. Vol. hll. No. 1350 



the same quantities of acid or alkali added 

 instead of comparing the behavior of proteins 

 at the same hydrogen ion concentration they 

 were not able to furnish the final proof for 

 the purely chemical character of the combina- 

 tions between ions and proteins, and nothing 

 prevented chemists from assviming that pro- 

 teins formed only adsorption comjwunds with 

 acids, bases, and neutral salts. 



The second reason for the failure to prove 

 the purely chemical character of the protein 

 compounds lay in the so-called Hofmeister 

 'series of ion effects. Hofmeister was the first 

 to investigate the effects of different salts on 

 the physical properties of proteins, and he 

 and his followers observed that the relative 

 effects of anions on the precipitation, the 

 swelling, and other properties of proteins was 

 very definite and that the anions could be 

 arranged in definite series according to their 

 relative efficiency, the order being independ- 

 ent of the nature of the cation. Similar 

 series were also found for the cations, though 

 these series seemed to be less definite. These 

 Hofmeister series were a puzzle inasmuch as 

 it was impossible to discover in them any 

 relation to the typical combining ratios of the 

 ions, and this lack of chemical character in 

 the Hofmeister series induced chemists to 

 explain these series on the assumption of a 

 selective adsorption of these ions by the 

 colloids. 



To illustrate this we will quote the order 

 which, according to Pauli, represents the 

 relative efficiency of different acids on the 

 viscosity of blood albumin, 



HCl > monochloracetic > oxalie > dieMoracetic > 

 eitrie > acetic > sulfuric > trichloracetic acid, 



where HCl increased the viscosity most and 

 trichloracetic or sulfuric least. In this series 

 the strong monobasic acid HCl is followed by 

 the weak monochloracetic acid, this is fol- 

 lowed by the dibasic oxalic acid; later follows 

 a weak tribasic citric acid, then the very 

 weak monobasic acetic acid, then the strong 

 dibasic sulfuric acid, and finally again a 

 monobasic acid, trichloracetic. Pauli is a 

 believer in the chemical theory of the be- 



havior of proteins but it is impossible to 

 harmonize his series of anions with any 

 purely chemical theory of the behavior of 

 proteins. 



The ion series of Hofmeister are no more 

 favorable for a chemical conception. Thus, 

 according to Hofmeister, gelatin swells more 

 in chlorides, bromides and nitrates than in 

 water, while in acetates, tartrates, citrates, 

 or sugar it swells less than in water. E. 

 Lillie arranges ions according to their de- 

 pressing effect on the osmotic pressure of 

 gelatin solution in the following way, 



CI > SO^ > ISrOg > Br > I > CNS. 



These series again betray no relation to the 

 stoichiometrical properties of the ions. As 

 long as these Hofmeister ion series were be- 

 lieved to have a real existence it seemed 

 futile to decide for or against a purely chem- 

 ical theory of the behavior of colloids since 

 even with a bias in favor of a chemical theory 

 the Hofmeister series remained a puzzle. 



The writer believes to have removed these 

 difficulties by using protein solutions of the 

 same hydrogen ion concentration as the 

 standard of comparison. In this way he was 

 able to show that acids, alkalies, and neutral 

 salts combine with proteins by the sam.e chem- 

 ical forces of primary valency by which they 

 combine with crystalloids, and that, moreover, 

 the influence of the different ions upon the 

 physical properties of proteins can be pre- 

 dicted from the general combining ratios of 

 these ions. The so-called Hofmeister series 

 have no real existence, being the result of the 

 fact that the older workers failed to measure 

 the most important variable in the case, 

 namely the hydrogen ion concentration of 

 their protein solutions, a failure for which 

 they can not be blamed since the methods 

 were not sufficiently developed. 



Pauli and a number of other workers 

 assume that both ions of a neutral salt are 

 adsorbed simultaneously by non-ionized pro- 

 tein molecules. If we consider the hydrogen 

 ion concentration of the proteins we can show 



