CRYSTALLINE FORMS OF HEMOGLOBIN 359 



which would very probably differ from one another in the morphology 

 of their crystals. In point of fact, however, the available number of 

 isomers would be very greatly restricted by the necessity of maintain- 

 ing unaffected the amino-acid groupings of the protein moiety, which 

 could not differ materially in different species without leading to de- 

 cided differences in the chemical behavior of the hemoglobins, which 

 have not been observed by any investigator. Further doubt is thrown 

 upon this interpretation of the facts by the observation of Hiifner, 

 recently confirmed with the utmost precision by Butterfield, Heubner 

 and Rosenberg, and Schumm, that the characteristic Absorption- 

 bands, and the ratio of the absorption of light in different parts of 

 the spectrum of hemoglobin are absolutely identical in species so far 

 removed from one another as the horse and man (Schumm) or the 

 rabbit, sheep, and hog (Heubner and Rosenberg). Now these are 

 properties which we would anticipate might be materially affected by 

 internal differences of atomic arrangement. 



Further reason for doubting the correctness of referring the differ- 

 ences of crystal structure displayed by the hemoglobins of different 

 animals to internal differences in the molecule of the hemoglobins is 

 supplied by the observation of Loeb and Brown that the crystal-form 

 of the hemoglobin of the mule is intermediate in character between that 

 of the horse and that of the donkey. For if we assume that each different 

 crystal-form represents a different internal atomic arrangement of 

 the hemoglobin molecule, then the number of such arrangements, even 

 if very great, must nevertheless be limited. The number of possible 

 forms of crystals must, therefore, also be limited, and, moreover, the 

 possible modifications of forms must be discontinuous, i. e., there must 

 exist forms between which no intermediate forms are possible. This 

 being the case it would be very remarkable indeed were the hybridi- 

 zation of two closely related species to lead to the synthesis of a new 

 isomeric variety of hemoglobin not yet appropriated by any existing 

 species of animal and, in addition, lying between the hemoglobins of 

 the parent-species. If analogous phenomena should be displayed by 

 all hybrids and by all varieties and mutations that might have arisen 

 or might conceivably arise in the future, we would have to admit that 

 the hemoglobins already recognizable as differing from one another in 

 crystalline form are only a small proportion of those which are realisable. 



A much more reasonable supposition is that embodied in the view 

 that the differences in crystal-form observed by Reichert and Brown 

 were attributable, not to the internal variation of atomic grouping in 

 the hemoglobin molecules, but to external variations in the milieu 

 from which they are crystallized. The technique adopted by Reichert 

 and Brown was to induce crystallization directly in the laked blood. 

 Now we know from the observations of the immunologists that the 

 blood-plasma from any species of animal differs antigenically from 

 that derived from any other species, and since all known antigens are 

 proteins, we infer that the proteins or, more probably, the compound 

 Protein Complexes in blood-plasmas derived from different species are in 



