October i8, 1889] 



SCIENCE. 



261 



of study by Selmi's work may be mentioned Brugnatelli, Zenoni, 

 and Cortez, who found an alkaloid resembling strychnine in decay- 

 ing corn-meal. At the same time, Gautier,.in France, was attack- 

 ing the problem, and independently, arrived at the same results, — 

 that alkaloids are produced by the decomposition of albuminous 

 substances. 



The first to actually separate and determine the chemical com- 

 position of an animal alkaloid was Nencki, in 1876. He obtained 

 from decomposing gelatine needle-shaped crystals of a salt to which 

 he gave the name " coUidin," and which he determined had the 

 formula CbHi jN. 



During the last five or six years the study of ptomaines has re- 

 ceived much attention on both sides of the Atlantic ; but no one 

 has done so much to develop methods of procedure, and put our 

 chemical knowledge of these substances on a firm scientific basis, 

 as Brieger. Of the ptomaines whose composition has been deter- 

 mined. Brieger analyzed nineteen, while Gautier and Etard come 

 next with three. 



The infectious diseases, at least those which are caused by mi- 

 cro-organisms (and those are the only ones we are now consider- 

 ing), may be classed in two divisions. 



First, we have those in which the organism invades the blood 

 and propagates there, and by so doing produces profound altera- 

 tions in that medium. Among such diseases may be mentioned 

 anthrax, malaria, relapsing fever, and certain forms of septicemia. 



The second class includes those diseases in which the micro- 

 organism does not develop in the blood, but only reproduces itself 

 in limited foci. Thus in typhoid-fever the specific organism grows 

 only in glandular structures in the walls of the intestines, and in 

 the mesenteric glands and the spleen ; in cholera the growth is con- 

 fined chiefly to the lumen of the intestines, though the walls of the 

 gut are sometimes invaded ; in abscesses and suppurating wounds 

 the pus-forming organisms are confined to the abscess, or the tis- 

 sues of the wound, and are not found in the blood ; and in sapras- 

 mia the organisms of putrefaction in most cases do not involve 

 the living tissue at all, but find their pabulum in blood-clots, exu- 

 dations, and spots of necrosis. 



It has been an interesting and important problem to discover 

 how micro-organisms actually produce the symptoms in these dif- 

 ferent affections. It has been variously attributed to the " me- 

 chanical irritation " of the microbes, to their occlusion of minute 

 vessels, to their consumption of certain elements in the blood or 

 tissues necessary to the physiological integrity of the host, and, 

 lastly, to the production of poisonous materials which re-act upon 

 the tissues. 



While there are some theoretical and experimental reasons for 

 believing that micro-organisms may occasionally act in all of these 

 ways, the evidence has of late been accumulating, as Dr. Chapin 

 has attempted to show, that the last-named method is by far 

 the most common and important. Even if there were no experi- 

 mental evidence, we should hardly be able to explain the consti- 

 tutional symptoms of the second class of infectious diseases in 

 which the organisms are strictly localized, except on the hypothesis 

 of the production of soluble substances which are taken up in the 

 circulation. 



But we know that there is much besides mere hypothesis which 

 would lead us to attach great importance to the role of the chemi- 

 cal products of bacterial life in the production of the symptoms of 

 the infectious diseases. In certain forms of septic disease the 

 demonstration is complete that the entire circle of symptoms is im- 

 mediately caused by the action of such substances. The experi- 

 ments of Bergmann, Hemmer, Weber, and, first and most impor- 

 tant of all, Panum, show that chemical substances, which can be 

 isolated, produce precisely the same set of symptoms that are 

 caused by the injection of untreated putrid material containing 

 living organisms ; and recently, since the perfection of bacterio- 

 logical methods, Roux, Chamberland, and Arloing have shown 

 that cultures of septic organisms produce substantially the same 

 results, whether the organisms are present or have been removed 

 by heating or filtration. And not only this, but Roux and Cham- 

 berland have obtained the same substances from the tissues of 

 animals suffering with the diseases concerning which the experi- 

 ments were made. 



In the formation of pus it has been demonstrated, that, in some 

 cases at least, it is the ptomaine produced by the organism which 

 induces the migration of the leucocytes. 



It is in regard to tetanus, however, that we have the most ac- 

 curate knowledge in regard to the mechanism of the production of 

 the symptoms. That this disease is caused by a bacillus, which 

 develops in wounds, and does not migrate into the blood-vessels, 

 is beyond question. From artificial cultures of this organism, and 

 also from the tissues of a human subject suffering from the dis- 

 ease, a ptomaine has been obtained which produces in animals the 

 identical symptoms of the disease ; and, furtherhnore, it has been 

 obtained in such purity that its chemical formula has been ac- 

 curately determined. 



Typhoid-fever and cholera do npt normally occur in the lower 

 animals, though the administration of their specific organisms un- 

 der certain conditions is followed by a set of symptoms called " ex- 

 perimental typhoid fever," and " experimental cholera." The ex- 

 periments of Sirotinin, and Beumer and Peiper, for typhoid-fever, 

 and of Gamaleia and Lowenthal for cholera, have shown that all 

 the essential features of these diseases are dependent upon the 

 soluble substances contained in cultures of the organisms. 



The experiments that have been made with anthrax, hog-cholera, 

 fowl-cholera, and erysipelas, while indicating to some degree the 

 importance of the r6!e played by soluble substances in these 

 diseases, have not given very complete or satisfactory results. 



As the subject of the essay is " The Role of Ptomaines in Infec- 

 tious Diseases," the action of other substances has only been briefly 

 alluded to ; but it must be remembered that a very large number 

 of substances besides those belonging to this particular chemical 

 group are elaborated by the growth of micro-organisms. We 

 have every reason to believe that the most important are, indeed, 

 of an alkaloidal nature : for the sepsin of Panum, and the tetanine 

 of Brieger, produce all the symptoms of septic poisoning and of 

 tetanus ; and cadaverine is, in and of itself, capable of producing 

 true suppuration. 



Nevertheless it is probable that such substances as sulphuretted 

 hydrogen, ammonic sulphide, phenol, etc., all elaborated by bacte- 

 rial life, have some influence upon the body. Moreover, the experi- 

 ments of De Christmas, Arloing, Rietsch, and Wooldridge, afford 

 very strong evidence that ferments of a proteid nature play a very 

 important part in the production of infectious diseases. The 

 ptomaines, like the vegetable alkaloids and the leucomaines, all 

 chemical allies, have a markedly selective action on the nervous 

 system ; and we may assume with a fair degree of probability 

 that many of the nervous phenomena, the delirium, stupor, trem- 

 blings, and paralysis of the infectious diseases are due to these sub- 

 stances. The action of typhotoxine, found in the cultures of the 

 typhoid bacillus by Brieger, and the ptomaine isolated by Hoffa 

 from anthrax cultures, are indications of this. 



One of the most common and important phenomena of the infec- 

 tious diseases is fever. That fever may be produced by ptomaines 

 is shown by Panum's experiments with sepsin, and Hoffa's with 

 the anthrax ptomaine. 



That the fever of the infectious diseases is frequently due to 

 these substances is very probable ; but that it may be due to other 

 materials or causes is also probable, and, in fact, quite certain. 

 Angerer and Edelberg have shown that fever can be caused by the 

 injection of blood and of fibrine ferment ; and Schmiedeberg ob- 

 tained like results with another proteid substance. 



Wood, Reichert, and Hare, Otto, Bergmann, and others have 

 shown that pepsin, trypsin, and pancreatin are all capable of pro- 

 ducing a rise in temperature ; so that it is highly probable that 

 proteid substances, as well as those of an alkaloidal nature, have 

 much to do with the production of febrile symptoms in the infec- 

 tious fevers. 



The experiments of Arloing and De Christmas would also show 

 that some pyretic substances are not readily diffusible, and are 

 probably of the nature of ferments. 



Another ro/e of the ptomaines and other soluble substances is 

 the preparation of tissues and fluids for the growth of microbes. 

 There is in the living body a constant tendency towards the de- 

 struction of all micro-organisms. This tendency varies greatly 

 from time to time, and can doubtless be greatly affected by the ac- 



