THE NATURE OF TOXINS 167 



the case of tetanus the fatal dose of the pure poison for a 

 guinea-pig must often be less than '000001 gr.), we can under- 

 stand how attempts by present chemical methods to isolate them 

 in a pure condition are not likely to be successful, and of their 

 real nature we know nothing. In a recent research Friedberger 

 and Moreschi have shown that the intravenous injection in the 

 human subject of a fraction of a loopful of a dead typhoid 

 culture gives rise to toxic symptoms, including marked febrile 

 reaction. Such injections are followed by the appearance of 

 agglutinating and bacteriolytic substances in the serum. These 

 results show that intracellular toxins may be comparable with 

 extra-cellular toxins so far as concerns the extremely small dose 

 sufficient to produce toxic effects. 



Amongst the properties of the extracellular toxins are 

 the following. They are certainly all uncrystallisable ; they 

 are soluble in water and they are dialysable ; they are pre- 

 cipitated along with proteids by concentrated alcohol, and also 

 by ammonium sulphate ; if they are proteids they are either 

 albumoses or allied to the albumoses ; they are often relatively un- 

 stable, having their toxicity diminished or destroyed by heat (the 

 degree of heat which is destructive varies much in different cases), 

 light, and by certain chemical agents. Their potency is often 

 altered in the precipitations practised to obtain them in a pure 

 or concentrated condition, but among the precipitants ammonium 

 sulphate has little if any harmful effect. Regarding the toxins 

 which are more intimately associated with the bacterial proto- 

 plasm we know much less, but it is probable that their nature is 

 similar, though some of them at least are not so easily injured by 

 heat, e.g. those of the tubercle bacillus, already mentioned. In 

 the case of all toxins the fatal dose for an animal varies with 

 the species, body weight, age, and previous conditions as to 

 food, temperature, etc. In estimating the minimal lethal dose 

 of a toxin these factors must be carefully considered. 



The following is the best method of obtaining concentrated extra- 

 cellular toxins. The toxic fluid is placed in a shallow dish, and ammonium 

 sulphate crystals are well stirred in till no more dissolve. Fresh crystals 

 to form a bulk nearly equal to that of the whole fluid are added, and the 

 dish set in an incubator at 37 C. over night. Next day a brown scum 

 of precipitate will be found floating on the surface. This contains the 

 toxin. It is skimmed off with a spoon, placed in watch glasses, and 

 these are dried in vacua and stored in the dark, also in vacua, or in an 

 exsiccator containing strong sulphuric acid. For use the contents of one 

 are dissolved up in a little normal saline solution. 



The comparison of the action of bacteria in the tissues in 

 the production of these toxins to what takes place in the gastric 



