26o 



SCIENCE. 



[Vol. XIV. No. 350 



THE ROLE OF PTOMAINES IN INFECTIOUS 

 DISEASES. 

 The trustees of the Fiske Fund, — Albert Potter, M.D., Che- 

 pachet; John W. Mitchell, M.D., Providence; William H. Palmer, 

 M.D., Providence, — with George L. Collins, M.D., Providence, as 

 secretary, at the annual meeting of the Rhode Island Medical So- 

 ciety, held June 13, 1889, announced that they had awarded a pre- 

 mium of two hundred and fifty dollars for the best essay on " The 

 Role of Ptomaines in Infectious Diseases," to an essay bearing the 

 motto, " Their poison is like the poison of a serpent." The author 

 was found to be Charles V. Chapin, M.D., of Providence, R.I. 



From Dr. Chapin's historical sketch we learn that the word 

 " ptomaine " (from ■^-cj/ia, " a corpse ") was first applied by Selmi 

 to basic substances derived from the putrefaction of organic nitro- 

 genous material. The ptomaines are of the same general chemical 

 composition as the vegetable alkaloids of pharmacy, and they are 

 not to be distinguished from them by chemical tests. Individual 

 alkaloids can, of course, be distinguished one from another, but 

 there is no sharp line of demarcation, and no general tests, which 

 seem to distinguish the ptomaines from the alkaloids. 



The former term is applied to those alkaloidal substances 

 which are produced by putrefactive decomposition ; that is, by the 

 action of micro-organisms. The alkaloids proper are produced by 

 changes going on within the living organism of plants. But they 

 have this in common, that they are both produced by a retrograde 

 metamorphosis of highly organized albuminoid material. 



The ptomaines are divided into two classes, according to their 

 chemical composition ; the first containing no o.xygen and volatile, the 

 second containing oxygen and corresponding to the fixed alkaloids. 

 The internal chemical composition, and the methods by which they 

 are isolated, belong rather to the domain of chemistry than pathol- 

 ogy. It is sufficient to say that they are separated from their 

 aqueous extracts by means of ether, chloroform, benzine, or other 

 non-miscible solvents, which are then evaporated, the residue 

 extracted, and the process repeated, and finally the different 

 ptomaines separated and isolated by precipitation with various 

 re-agents suitable for the purpose. 



A history of the various experiments and observations which 

 gradually led up to a correct understanding of the chemistry and 

 pathology of these compounds is most important in this connection. 

 Haller, in the middle of the last century, was the first to experi- 

 ment in regard to the nature of putrefactive poisons, determining 

 that the aqueous solutions of putrid substances would cause death 

 when injected into the veins of animals. Gaspard, in an article 

 published in 1S22, related similar experiments, and noted among 

 the symptoms, vomiting, twitching and convulsions, hiccough, and 

 great thirst. He found the intensity of these symptoms increased 

 with the amount of the dose : in the majority of cases, death oc- 

 curred within twenty-four hours. He determined by experiment 

 that neither CO,, nor HoS, nor NH3 could produce such symp- 

 toms, but believed that it must be some other chemical substance. 

 Gaspard showed that the blood from an animal thus infected could 

 infect another, and he referred to the similarity of the nature of 

 this infection to that of the specific ^infectious 'fevers. Somewhat 

 similar results, which he obtained by the intra-venous injection of 

 pus, he attributed to the products of septic processes, which had 

 begun in the pus. 



Magendie found that putrid materials introduced into the ali- 

 mentary canal were not productive of any such marked symptoms 

 as when introduced into the veins, and he therefore concluded that 

 the mucous membrane acted as a sort of filter to separate the poi- 

 sonous elements ; and he believed that the respiratory mucous 

 membrane had the same function, for he exposed pigs, fowls, rab- 

 bits, and dogs to putrid exhalations, and only the latter suc- 

 cumbed, and they only gradually, giving no evidences of acute 

 poisoning. 



Leuret repeated the injection experiments of Gaspard and Ma- 

 gendie, and accepted their views of the chemical nature of the sep- 

 tic poison ; but he did not succeed in isolating it, or determining 

 its nature. 



Vitchow also showed that septic infection quickly caused vomit- 

 ing, diarrhoea, muscular weakness, and convulsive symptoms, with 



great heart weakness, and death in a few hours. Beck repeated 

 these experiments, and determined the presence of sulphide of am- 

 monia in the putrid material, and showed that it would also pro- 

 duce a fatal result. 



Stich performed similar experiments, and came to the same con- 

 clusions as to the chemical nature of the poison. Then followed 

 the experiments of Panum in 1850. He was the first to actually 

 determine the chemical nature of the septic poison by separating- 

 it from septic solutions. 



Weber v. Hemmer repeated Panum's experiments with substan- 

 tially the same results, and Thiersch, Stich, and Schwenninger fol- 

 lowed in the same path ; but none of their work was as thorough 

 and satisfactory as Panum's. 



In 1866 Bence Jones and Dupre separated from the decomposing 

 organs of men and animals, especially from the liver, an amor- 

 phous substance to which they gave the name " animal chinoidin," 

 from its presenting a fluorescence like quinia when dissolved in 

 dilute sulphuric acid. 



In 1868 Bergmann succeeded in isolating a putrid poison, and, 

 in company with Schmedeberg, he separated a poisonous substance 

 from putrid yeast. This substance they obtained by a ciicuitous- 

 process, in the shape of minute crystals of tlic sulphate. Its watery 

 solution produced in dogs the symptoms - ov,"'C D0.3CMng, such 

 as vomiting, diarrhoea with bloody s' joIs, and, on autopsy, there 

 was ecchymosis of the stomach ana intestines. In frogs, also, se- 

 vere symptoms were produced. This poisonous substance was 

 called " sepsin," but was not obtained in sufficient quantity to ad- 

 mit of a determination of its chemical structure. 



In 1869 Zuelzer and Sonnenschein separated from macerated 

 bodies a crystalline substance which exhibited all the alkaloidal re- 

 actions. Physiologically it seemed to be a narcotic, somewhat like 

 atropine, and resembled the so-called " sausage poison." It pro- 

 duced dilatation of the pupil, muscular paralysis, and acceleration 

 of the cardiac pulsations. The authors obtained this substance by 

 the ether and alcohol process for separating alkaloids, called Otto- 

 Stas's method, and also by diffusion and e.xtraction with glycerine. 

 Rorsch and Fassbender obtained from a cadaver a non-crystal- 

 lizable substance resembling digitaline in its properties, but not 

 having its bitter taste. 



Schwanert, at about the same time, obtained from a dead body 

 an oil with strong basic properties, and which smelled like propyl- 

 amine. 



Marquardt, and later Hager, obtained a substance to which was 

 given the name " septicin," and which Hager believed was a mix- 

 ture of amylamine and caprylamine. Lieberman also obtained a 

 similar substance from the^ stomach of a person who had been 

 poisoned by arsenic. The physiological action of none of these 

 was determined. 



Krebs-Brandes obtained a coniine-Iike substance, and found that 

 .007 of a gram injected into a frog killed it instantly, and .044 of a 

 gram had the same effect on a pigeon in a few minutes. 



Brouardel and Boutmy found in a decomposed goose a substance 

 which gave re-actions, like confine, and which produced toxic 

 symptoms. 



According to Husemann, there are a large number of cadaveric 

 alkaloids which resemble confine. 



Wolckenhaar separated an amorphous base, which resembled 

 nicotine, but had no toxic properties. 



Moriggia and Battistini found in the watery extract of dead 

 bodies a poison somewhat like curara ; which, however, gradually 

 lost its toxic properties the more it was purified. 



Selmi, in Italy, while engaged as a medico-legal expert, became 

 convinced that alkaloidal substances were formed in the human 

 body after death by the putrefactive processes there taking place. 

 From 1870 till the day of his death, Selmi devoted himself to the 

 study of these substances ; and he determined the occurrence of 

 several alkaloids similar to morphine, confine, atropine, and del- 

 phine, and other vegetable alkaloids, but he did not succeed in 

 separating any of them with sufficient purity to permit of chemical 

 determination. Selmi, however, did much to encourage and ad- 

 vance the study of these substances, and definitely determined that 

 they were produced by the action of microbes on proteid tissue. 

 Among the other Italians who were encouraged to pursue this line 



