VIII 



PREFACE. 



heredity, mutations, the influences of food and environ- 

 ment, the differentiation of sex, and other great prob- 

 lems of biology, normal and pathological. 



"'To what extent this hypothesis is well founded 

 may be judged from this partial report of the results 

 of our investigations: It has been conclusively shown 

 not only that corresponding hemoglobins are not identi- 

 cal, but also that their peculiarities are of positive generic 

 specificity, and even much more sensitive in their dif- 

 ferentiations than the " zooprecipitin test." Moreover, 

 it has been found that one can with some certainty pre- 

 dict by these peculiarities, without previous knowledge 

 of the species from which the hemoglobins were derived, 

 whether or not interbreeding is probable or possible, and 

 also certain characteristics of habit, etc., as will be seen 

 by the context. The question of interbreeding has, for 

 instance, seemed perfectly clear in the case of Canidae 

 and Muridae, and no difficulty was experienced in fore- 

 casting similarities and dissimilarities of habit in Seiu- 

 ridsB, Muridse, Pelidse, etc., not because hemoglobin is per 

 se the determining factor, but because, according to this 

 hypothesis, it serves as an index (gross though it be, with 

 our present very limited knowledge) of those physico- 

 chemical properties which serve directly or indirectly to 

 differentiate genera, species, and individuals. In other 

 words, vital peculiarities may be resolved to a physico- 

 chemical basis.' 



" Before and since the inception of the foregoing 

 research, data have been slowly accumulating which 

 point more and more strongly to the extremely import- 

 ant interrelationships that exist between the intramolecu- 

 lar configurations of various substances that play active 

 roles in life's processes and the configurations of proto- 

 plasm. Hence, any progress in the application of stereo- 

 chemistry to metabolic processes brings us closer to an 

 understanding of those peculiar mechanisms of proto- 

 plasm which give rise to the phenomena which in the 

 aggregate -constitute life in its normal and abnormal 

 manifestations. 



" Hemoglobin, next to protoplasm, is unquestionably 

 the most important organic substance of vertebrate life, 

 and in conjimction with the stroma with which it is asso- 

 ciated is an active functionating protein, the main func- 

 tion of which is the conveyance of oxygen from the 

 external organs of respiration to the internal organs of 

 respiration or the tissues generally. Starch is similarly 

 an extremely important constituent of a vast number of 

 forms of plant life, but its role in vital processes, while, 

 on the whole, as essential to the continuance of life, is 

 of an entirely different character. Moreover, the general 

 and special characters of these substances in relation to 

 those of the bodies which originate them, and the mechan- 

 isms of their formation, are likewise strikingly different. 

 Hemoglobin constitutes nearly the whole of the erythro- 

 cyte or red-blood corpuscle, and that portion of the ery- 

 throcyte which is not this substance may properly be 

 regarded as being in the nature of an adjunct, but 

 nevertheless essential. In early embryonic life the ery- 

 throcytes are nucleated and probably derived directly 

 from the mesoblastic elements, and they increase in num- 



ber by mitosis. Later, proliferation occurs in all parts 

 of the circulation, in certain capillary areas more than 

 others, especially in those of the liver, spleen, and bone- 

 marrow. During the progress of fetal development the 

 erythrocytes, primarily spherical and nucleated, in time 

 lose their nuclei, and become smaller, and take on the 

 peculiar disk or cup-shaped form of postnatal life. After 

 birth the red bone-marrow is the chief or sole seat of 

 formation of erythrocytes. It is the common conception 

 that in this structure these corpuscles arise from nucle- 

 ated red cells which exist at first as colorless, nucleated 

 erythroblasts, and subsequently as smaller, denser, 

 colored, nucleated normoblasts. The former, which are 

 looked upon as the hereditary representatives of the 

 embryonal erythrocytes, are generally conceived to be 

 converted into normoblasts by mitosis, and the latter in 

 turn to become ordinary erythrocytes upon the disappear- 

 ance of the nuclei by solution or extrusion. It is, how- 

 ever, more likely, as suggested in 1883 by Malassez, and 

 very recently (1912) by the investigations of Bmmel by 

 means of plasma cultures, that the erythrocyte of late 

 fetal and post fetal life is formed from the cytoplasm 

 of the erythroblast by a simple process of budding and 

 detachment.* According to either conception the ery- 

 throcyte is a separated portion of the mother substance 

 that has been set free in a highly specialized life-sustain- 

 ing medium, but in a distinctly modified form, inasmuch 

 as it has a much higher hemoglobin content and is lacking 

 in the amoeboid activities and power of reproduction of 

 the parent substance, the latter differences being readily 

 accounted for in the absence of nuclear matter. Starch, 

 on the other hand, is a synthetic product of metabolic 

 activity which bears no resemblance to the protoplasm 

 that gave rise to it, and which is destined to serve an 

 entirely different purpose from that of hemoglobin in the 

 life-history of the organism. With hemoglobin as it 

 exists associated with the stroma in the erythrocytes we 

 are dealing with an active, living, functionating, highly 

 specialized form of protoplasm; with starch, we deal 

 with an absolutely inert, non-living, non-functionating, 

 extremely complex carbohydrate in the nature ofastored- 

 up pabulum, and a synthetic product of plastids which 

 are specialized forms of protoplasm. In the hemoglobin 

 research it was shown that the hemoglobin molecule is 

 modified in specific relationship to genus, species, etc., 

 which may be taken to mean that the form of protoplasm 

 that is expressed by the term erythrocyte is correspond- 

 ingly stereochemically modified ; with starch it has been 

 found, as will be seen by the context, that the molecule 

 is likewise changed in specific relationship to genera, 

 species, etc., which accordingly may also be taken to 

 mean that during synthesis the products of activity are 

 altered in their molecular peculiarities in specific rela- 



*See Science 1912, xxxv, 873; 1914, xxxix, 334. Kite (Proc. Soc. 

 Exp. Biol. Med., 1914, xi, 112) and Oliver (Science, 1914, XL, 

 648) have found that erythrocytes can be so modified structur- 

 ally and vitally as to have ciliate or flagellate processes, and Oliver 

 has shown that some of the latter exhibit a high degree of irrita- 

 bility in relation to mechanical stimulus. 



