W. KAUZMANN 11 



definition has its advantages and its disadvantages. A definition that is 

 based directly on simple experimental criteria has the apparent advantage 

 that it is expressed in operational terms, so that in using it the experimenter 

 will not be likely to have much difficulty in concluding whether or not de- 

 naturation has occurred under a particular set of conditions. A definition 

 in terms of changes in structure may be difficult to apply because there 

 are not many methods of detecting changes in the state of folding of the 

 polypeptide chain — especially if these changes are slight. Therefore the 

 definition in terms of loss of solubility and activity is likely to appeal to 

 the man in the laboratory. On the other hand, a definition in structural 

 terms focuses attention on the essential changes that take place in the 

 protein molecule and therefore comes to grips with a more fundamental 

 aspect of the problem. Furthermore, the existence of reversible denatura- 

 tion may seriously limit the 'experimental' definition in an undesirable 

 way, as w'e shall see. 



The widespread use of these two very different and equally legitimate 

 types of definition has lead to confusion and has made some workers 

 suggest that the term 'denaturation' be discarded altogether. The word 

 is so widely used, however, and there is such a need for some term to 

 designate the phenomenon, that it is not likely to be dropped. If we recog- 

 nize that the term has several legitimate meanings, and if in using it we 

 always make it clear just which meaning is intended, much of the con- 

 fusion that the word sometimes seems to cause should disappear. Besides, 

 if we are going to discard the word, a new word will have to be invented. 

 This hardly seems advisable at the present time because, as Anson has 

 said ( 1 ) , we do not yet know enough about the phenomenon to be able to 

 define precisely the word that we use to describe it. It seems much simpler 

 to continue to use the word with the dual meanings that have been given 

 to it in the past, always making clear which meaning is intended. 



It might seem unnecessary to devote so much space to this matter of 

 defining a term that almost everyone thinks he understands, especially 

 when no unique definition has been finally decided upon. The concept of 

 denaturation plays a very important role in discussions of the stability of 

 proteins, however, and we can come to very different conclusions, depend- 

 ing on how we choose to define the phenomenon. For instance, serum al- 

 bumin can be exposed to pH 2 or to 8m urea for long periods without losing 

 its solubility in water at its isoelectric point. Exposure of ovalbumin to the 

 same conditions leads to a rapid loss of its solubility at the isoelectric 

 point. Therefore, according to the 'experimental' definition of denatura- 

 tion, we should conclude that ovalbumin is much easier to denature than 

 is serum albumin. On examining the optical rotations and the intrinsic 

 viscosities of the two proteins while they are exposed to the denaturing 



