APPLICATIONS OP RESULTS OF RESEARCHES. 



361 



found that one form is sweet while another is tasteless ; 

 another may be odorous, but its enantiomorphous form 

 without odor. 



To the foregoing there may be added examples of 

 other substances that exist in several forms, but which 

 physico-chemically belong to a different class. Thus, 

 nitroglycerine may exist in forms that are so different 

 that under given conditions of temperature and percus- 

 sion one is explosive and the other non-explosive. Dif- 

 ferences in substances which are found in allotropic 

 forms may be as marked as in any of the preceding illus- 

 trations, as, for instance, in the case of phosphorus, which 

 is familiar as the yellow, white, black, and red varieties, 

 all of which with the exception of red phosphorus are 

 exceedingly poisonous, while the latter is inert. The 

 ortho, rneta, and para forms of a given substance may 

 exhibit more or less marked physiological and toxicologi- 

 cal variations, and so on. 



The explanation of the remarkable differences shown 

 by these substances, which differences are paralleled by 

 those manifested by the lethal and inocuous proteins of 

 the serpent, the pepsins, the protamins and the red-blood 

 corpuscles, is to be found in the results of two independent 

 but intimately related lines of physico-chemical re- 

 search: (1) The investigations of Van't Hoff and LeBel 

 and subsequent observers which have laid the foundation 

 of a new, and to the biologist and physician an extra- 

 ordinarily important, development of chemistry known 

 as stereochemistry a department that treats of the 

 arrangements of the atoms, groups and masses of mole- 

 cules, or in other words of intramolecular arrangement 

 or configuration of molecular components in the three 

 dimensions of space. (2) The investigations of Willard 

 Gibbs and others which have given us the " phase rule,'' 

 which defines the phases or forms in which a given sub- 

 stance or combination of substances may exist owing to 

 differences in intramolecular and extramolecular ar- 

 rangements and concentration of their components in 

 relation to temperature and pressure. 



According to stereochemistry a given substance may 

 exist in multiple forms dependent upon differences in the 

 configuration of the molecule, all of which forms have 

 in common the fundamental chemical characteristics of 

 a given prototype, yet each may have certain properties 

 which positively distinguish it from the others. Theo- 

 retically, such substances as serum albumin, serum glo- 

 bulin, hemoglobin, starch, glycogen, and chlorophyl may 

 be produced by nature in countless modified forms, owing 

 to differences in intramolecular arrangements. Miescher 

 has estimated that the serum globulin molecule may exist 

 in a thousand million forms. Substances that exist in 

 such multiple forms of a prototype are distinguished as 

 stereoisomers. The remarkable fact has been noted by 

 Fischer and others that stereoisomers may exhibit as 

 great or even greater differences in their properties 

 than those manifested by even closely related isomers, 

 which latter in comparison with stereoisomers are dis- 

 tantly if at all chemically related. As already instanced, 

 so slight a change in molecular configuration as gives 

 rise to dextro and laevo forms may be sufficient to cause 

 definite and characteristic and even profound differences 

 in physical, nutritive, and physiological properties. 



In accordance with the " phase rule " a substance 

 or a combination of substances may exist in the form of 



heterogeneous or homogeneous systems, a heterogeneous 

 system consisting of a number of homogeneous systems, 

 each of which latter is a manifestation of an individual 

 phase and distinguishable from the others by physical, 

 mechanical, chemical, or physiological properties. The 

 number of phases of a heterogeneous system increases 

 with the number of component systems and the number 

 of the latter is in direct relationship to the number of 

 independent variable constituents. Therefore, by means 

 of variations of either or both intramolecular or extra- 

 molecular arrangement the number of forms of a sub- 

 stance or combination of substances may range from 

 few to infinite. 



Our means of differentiating stereoisomers are, on 

 the whole, limited, and for the most part crude, and 

 while it has been found that differences so marked as 

 those referred to may be detected by the ordinary pro- 

 cedures, it seems obvious that the inherent limitations of 

 such methods render them inadequate where a large 

 number of stereoisomerides or related bodies which may 

 exhibit only obscure modifications are to be definitely 

 differentiated, so that other and more sensitive methods 

 must be sought, or at least special methods that are 

 adapted to exceptional conditions. The results of much 

 preliminary investigation in this direction led in one 

 research to the adoption of the crystallographic method, 

 especially the use of the polarizing microscope, which 

 in its very modern developments of analysis has demon- 

 strated that substances which have different molecular 

 structures exhibit corresponding differences in crystal- 

 line form and polariscopic properties ; and, moreover, 

 that the " optical reactions " may be found to be as 

 distinctive and as exact analytically as the reactions 

 obtained by the conventional methods of the chemist. 

 Furthermore, the necessities of the hypothesis demanded 

 the selection of a substance for study of a character 

 which upon theoretical grounds might be expected to 

 exist in nature widely distributed and readily procura- 

 ble, and, as a consequence, hemoglobin was selected. 



In the study of the hemoglobins the author had as a 

 co-worker Professor Amos Peaslee Brown.* Hemoglo- 

 bins were examined from over 100 animals, representing 

 a large variety of species, genera, and families. From 

 the data recorded certain facts are especially conspic- 

 uous, among which may be mentioned the following : 



1. The constant recurrence of certain angles, plane 

 and dihedral, in the hemoglobins of various species, even 

 when the species are widely separated and the crystals 

 belong to various crystal systems. This feature indi- 

 cates a common structure of the hemoglobin molecules, 

 whatever their source. 



2. The constant recurrence of certain types of twin- 

 ning in the hemoglobins, and the prevalence of mimosie. 

 This has the same significance as the foregoing. 



3. The constancy of generic characters in the crys- 

 tals. The crystals of the various species of any genus 

 belong to a crystallographic group. When their charac- 

 ters are tabulated they at once recall crystallographic 

 groups of inorganic compounds. The crystals of the 

 genus Felis constitute an isomorphous group which is as 

 strictly isomorphous as the groups of rhombohedral and 

 orthorhombic carbonates among minerals, or the more 



* Carnegie Inst. Wash. Pub. No. 116. 



