ONTOGENETIC VARIATION 319 



and salt, and /3 is the logarithm of the solubility in the absence of salt and 

 reflects the amphoteric nature of the protein. The data included in Table 

 VIII constitute the most extensive series carried out in one laboratory. 

 Values are also available for the carboxyhemoglobins of ox {31S8), man, 

 and horse {10^2) and for the myocarboxyhemoglobin of horse {1987). 



5.4. Other Protein Reactions 



A number of other reactions of the oxygen carriers are known which 

 depend on the protein portion of the molecule and have been used to show 

 generic differences. These include alkali resistance and oxygen aflSnity. We 

 shall consider these in subsequent sections. 



6. VARIATION OF PROTEIN WITHIN A SPECIES 



6.1. Ontogenetic Variation 



6.1.1. Fetal Hemoglobin. The existence of a difference between the 

 oxygen affinity of fetal and maternal blood has been known for some 

 time {cf. Barcroft, 11^3), and is of considerable functional importance 

 (c/. Section 9.). Although the changes occurring in the maternal 

 blood during pregnancy could be explained by changes in the pH of 

 the blood, this was not possible with fetal blood and the existence 

 of "fetal" hemoglobin was postulated {1J^7). While the dissociation 

 curve of the fetal hemoglobin could be described mathematically in 

 terms of K and n in the Hill equation, this merely summarizes the 

 integrated effects of the environment and the constitution of the 

 pigment in the dissociation curve. As has been pointed out pre- 

 viously, the difference may be due to the influence of the micro- 

 environment, or to differences in the actual protein. 



6.1.2. Alkali Resistance. The measurement of the velocity of 

 denaturation by alkali provided evidence that differences were present 

 in the protein. The early observations of Korber in 1866 {1561), 

 subsequently dev^eloped by von Kriiger {1581) and other workers, 

 showed that generic differences are found between the rates at which 

 different hemoglobins are denatured by alkali. The investigations of 

 von Kruger {1582), Bischof {282), Haurowitz {1158,1159), and Brink- 

 man and co-workers {338) showed that similar differences were 

 present between the pigments of the fetal and maternal human, the 

 fetal hemoglobin being much more alkali resistant than the maternal 

 pigment. The latter workers developed a photoelectric method 

 which enabled them to work with mixtures of pigments of differing 

 alkali resistance. Discontinuities in the rate of disappearance of 



