APPLICATIONS OF PRINCIPLES TO PHARMACODYNAMICS. 339 



plants are expressions of molecular peculiarities, that such peculiarities should be shown 

 in intlivitlual substances as well as in the cellular aggregates that constitute the basic data 

 of the systematic botanist; and, moreover, inasmuch as it has been found in these researches 

 that the starches are modified in relationship to botanical peculiarities, and hemoglobins 

 in relation to zoological peculiarities (and incidentally the same relationships in the case 

 of glycogens and certain other complex synthetic metabolites), that there is adequate 

 justification for assuming that corresponding modifications will be found to exist in alka- 

 loids. It would therefore seem improbable that such complex organic substances as hyos- 

 cyamine, strychnine, and other alkaloids, which in each case have been obtained from 

 different species, and in some instances from different genera and even different families 

 and orders, exist in single forms, but rather that each substance exists in as many stereoiso- 

 meric forms as there are different botanical sources of origin. For instance, hyoscyamine 

 has been obtained from Hyoscyamus niger, Atropa belladonna, Datura slramonium, Scopolia 

 carnioUca, Duboisia mijoporoides, Anisodus luridus, and Lacluca saliva, and also from other 

 species of some of the genera represented. Here are seven genera that belong to two 

 families {Solanacea; and Compositw) that are so distantly related as to be assigned to dif- 

 ferent orders (Polcmoniales and Valerianales). That stereochemic differences have not 

 been recorded, or that subtle physiological differences may not have been obser\-ed in so 

 virulent a poison, is by no means evidence in disproof of the hypothesis of different stereo- 

 isomeric forms. In fact, our knowledge of the chemical constitution of alkaloids is gener- 

 ally very meager, and is not only being added to but accepted statements are being modi- 

 fied or entirely discarded. A few years ago hyoscyamine and atropine were given different 

 molecular formula", but now they are recognized as stereoisomers; piturine (C10H1GN2) from 

 Duboisia hopivoodii was believed to be identical with nicotine (Ci„Hi4N2), but is now recog- 

 nized as being a distinct individual; and the statement is frequently found that a given 

 plant species contains poisons which resemble, those of another of the same or of a related 

 genus. Such instances might be considerably multiplied in order to show not only the 

 superficiality of our knowledge of the chemistry of the toxic constituents of plants, but in 

 justification of the hypothesis of the existence of such substances in stereoisomeric forms. 



Moreover, as instanced in this memoir, and recorded in much subseciuent in\estigation 

 as yet unpublished, hybridization has the effect, in both plants and animals, of causing 

 definitely distinctive differences in the offspring in both gross and molecular properties, 

 so that, as regards especially the latter, the starch or hemoglobin, etc., can easily be dis- 

 tinguished from the corresponding substance of the parents. It would follow from the 

 foregoing, as a corollary, that given medicinal substances may, by hybridization, be modi- 

 fied in their physiological properties because of stereochemic changes. 



In the Introduction (page 8 et seq.) attention is directed to the extremely important 

 fact that slight stereochemic differences may be manifested in more or less marked varia- 

 tions in physiological actions, as have been recorded in the nicotines, cocaines, hyoscines, 

 hyoscyamines, and other organic substances; and, moreover, that under conditions similar 

 to or identical with those which exist in plants there may occur a transmutation of one 

 stereoisomeric form into another. In supplementation of what is there stated, it may be 

 of value to refer to certain facts of much significance: Atropa belladonna yields both 

 atropine and hyoscyamine, the former being the racemic form of the latter, while the latter 

 is kevo-rotatory (dextro-hyoscyamine is an artificial base). It was a bafHing problem 

 for years why the jiroportion of these two substances obtained from given specimens of 

 belladonna varied with differences in the laboratory methods used in their preparation, and it 

 was finally discovered that there occurred a ready transmutation of the hyoscyamine (hevo- 

 rotatory) into atropine (racemic) in the presence of fusion, a weak alcoholic solution of 

 sodium hydroxide, ammonia, etc. Another instance of especial interest is recorded in 

 the researches of Lanterer with the active principles of Duboisia. He found that the old 



