November 28, 1902.] 



SCIENCE. 



853 



Nogiichi, as it may be that a similar toxin 

 is produced by certain bacteria, and under 

 still other conditions. As is well known, 

 one of the most striking lesions resulting 

 from poisoning by certain venoms is the 

 occurrence of abundant haemorrhages in 

 various tissues of the body. This efEeet 

 has been generally attributed to the direct 

 action of venom on the red corpuscles and 

 On the coagulability of the blood, but the 

 experiments of Flexner and Nogiichi indi- 

 cate that these haemorrhages are due to the 

 presence in venom of a cytotoxin which has 

 the power of dissolving endothelial cells — 

 in other words, an endotheliolysin. Dr. 

 Flexner suggests the name ' hfemorrhagin ' 

 for this special toxin which causes extra- 

 vasations of blood through its direct solvent 

 action upon capillary endothelium, an 

 effect which is readily demonstrated under 

 the microscope. It is hardly necessary for 

 me to stop to emphasize the clinical and 

 pathological importance of the discovery 

 of an endotheliotoxin, a kind of poison 

 which may prove to be of special signifi- 

 cance in the interesting group of hsemor- 

 rhagic infections, and perhaps also in pur- 

 pura and kindred affections. 



The foregoing newly-discovered facts, 

 which I have sketched only in bare outline, 

 illustrate in a striking way the fruitfulness 

 of methods and conceptions which we owe 

 to recent studies of immunity. The results 

 of these investigations, however, are signifi- 

 cant beyond the mere facts disclosed, impor- 

 tant as these are. They have for the first 

 time revealed in normal toxic secretions, 

 readily introduced under conditions of 

 nature into the tissues of man and animals, 

 cellular poisons akin to the complex hfemo- 

 lysins, neurotoxins, and other cytotoxins of 

 immune and some normal serums, which 

 have aroused so much interest and experi- 

 mental study during the past four years. 

 The most noticeable difference between the 

 venom cytotoxins and those hitherto ob- 



served in immune serum is the far greater 

 resistance to heat of the intermediary 

 bodies of the former; but we are already 

 acquainted with considerable variations in 

 the sensitiveness to heat both of different 

 intermediary bodies and of complements. 

 That snake venom should contain only one 

 half of the complete poison, the other and 

 the really destructive half being widely 

 distributed in the blood and cells of man 

 and of animals, is an instance of a curious 

 kind of adaptation, of interest from evolu- 

 tionary, as well as from other points of 

 view. 



In consideration of the often emphasized 

 analogies between venom toxins and bac- 

 terial toxins, these facts render it highly 

 desirable to make a systematic search of 

 bacterial cultures by proper methods and 

 under suitable conditions for complex cyto- 

 toxins. At present substances of this na- 

 ture are not known to exist in our cultures. 

 There have been discovered, however, 

 within the past three or four years certain 

 bacterial toxins which have a curious re- 

 semblance in some of their properties to 

 the complex antibodies of blood, although, 

 so far as they have been carefully studied, 

 they appear to have the simpler constitu- 

 tion of the soluble toxins, like those of 

 diphtheria and of tetanus. I refer to the 

 bacterial haamolysins, leucolysins, haemag- 

 glutinins, precipitins and coagulins. There 

 is no reason to suppose that this list ex- 

 hausts the number of those actually pres- 

 ent, for it is evident that it includes chiefly 

 bodies readily demonstrable in test-tube ex- 

 periments. It would be surprising if cyto- 

 toxins which act specifically upon red and 

 white corpuscles were the only ones of this 

 class produced by bacteria; in fact, we 

 have every reason from pathological ob- 

 servations to believe the contrary. 



It has become evident that more refined 

 methods than mere observation of the 

 coarse effects of injecting into animals 



