ENDOTOXINS 123 



Vaughan has devised a method of growing massive cultures on solid 

 media several square yards in extent, removing the bacteria with sterile 

 salt solution, and digesting the bacterial masses with an excess of a 2 

 per cent, solution of caustic alkali in absolute alcohol. 



In the body, the endotoxins are probably liberated either by autolysis 

 or by disintegration through the bacteriolysins, complements, or enzymes 

 of the body-cells and fluids. 



Nature of Endotoxins. Owing to their insoluble nature, endotoxins 

 in pure form and free from other products of bacterial activity, cannot 

 be obtained. As a result, their chemical nature and structure are un- 

 known. Tuberculin, which was formerly believed to be an albumose, 

 may be produced in a protein-free medium; it seems probable that this 

 substance is of the nature of a polypeptid, giving no biuret reaction, but 

 being destroyed by pepsin and trypsin (Laevenstein and Pick x ). Whether 

 or not tuberculin is an endotoxin liberated upon the disintegration of the 

 bacilli is unknown. Pick regards it as a secretory product closely 

 related to the true toxins. It is probable that some toxin is actually 

 secreted into the culture-medium, and that the major portion, which is 

 of a somewhat different nature, is intimately related to the constituents 

 of the bacterial cells. 



There is little doubt but that endotoxic substances are highly poison- 

 ous, and that they are chiefly responsible for the characteristic symptoms 

 of diseases produced by the bacteria that contain them. Whether, 

 however, they are actually preformed definite and specific constituents 

 of bacteria, or merely the poisonous products of disintegration of the 

 bacterial proteins, is still undecided. It would appear that bacteria 

 produce and contain toxic substances. When, owing to the peculiar 

 structure of the bacterial protoplasm or nature of the toxic substance 

 itself, the toxin can diffuse readily into a surrounding medium, the toxic 

 substance is known as a true, soluble, or extracellular toxin; when the 

 toxin enters into combination with the bacterial protoplasm, it becomes 

 known as an endotoxin. This union of toxin and bacterial protoplasm 

 may be so firm as to render the toxic substance inseparable from the 

 bacterial protein. The various toxic substances or toxins differ, there- 

 fore, according to their diffusibility through the membrane of bacterial 

 protoplasm, or their power of combining with these protein substances, 

 or both factors may be operative. 



Satisfactory antitoxins for endotoxins have not been produced, and this 

 is an important point in differentiating between a true toxin or an endotoxin 

 of any particular microorganism. Animals immunized against endotoxin 

 1 Biochem. Zeit., 1911, 31, 142. 



