February 21, 1895] 



NATURE 



403 



specimens the protoplasm is more deeply tinted than in the 

 centre. This organism grows singly or in groups, or felted to- 

 gether to (orm a net-work ; it may occur in irregular masses of 

 considerable size. When these hacilli have been growing (or some 

 time on an artificial nutrient medium, they appear to be segmented, 

 the stained materiil accumulating in small round nodultrs placed 

 at intervals wiihin a kind of membrane which is only very deli- 

 cately tinted. During the past five weeks I have examined about 

 600 specimens taken from the throats of diphtheria patients, and 

 I may say that in nearly every case where the disease has been 

 diagnosed by the physician in chnrire, as being one of diph- 

 theria, these typical bacilli have been found, whilst in those cases 

 in which there was any doubt as to the nature of the disease, 

 similar bacilli wf re found in some, but not in oihers. 



This is of importance, because we shall find that this bacillus 

 gives us the sulistance with which animals are rendered immune 

 to the attacks of the bacillus itself, these immune animals in 

 turn supplying the anti'oxic serum. To prove that this bacillus is 

 really the cause of the disease, Loeltler, in an elaborate series of 

 expeiiment";, inoculated the pure cultures of the bacillus grown 

 on artificially prepared media, into animals ; he was thus able 

 to set up characteristic lesions, especially if he took the pre- 

 liminary precaution to abrade slighily the mucous membrane, 

 thus as it were ploughing the ground before scattering the seed. 

 On such abraded surfaces llie bacilli grew very luxuriantly, and 

 false membranes were produced ; in these lesions the hacilli could 

 afterwards he found and again separated in pure cultures, whilst 

 the characteristic toxic symptoms of diphtheria weie in each case 

 experimented upon, repeated with the utmost fidelity. Loeltler 

 also pointed out a mo>t important lact in conneciion with the 

 presence of the organism in the body. He found that it was 

 strictly confined to ihe local wounds or lesions in the ihroatand 

 posterior part of the nose, and he was also able to prove that in 

 this position these organisms commenced to manufacture most 

 virulent poisons, which, unlike the bacilli, can become difiused 

 throughout the body. Klein and Sydney Martin in this country 

 have boih made very valuable contributions to our knowledge, 

 the former concerning the bacteriology of the disease, the latter 

 in regard to the chemical action on the tissues of the toxic or 

 poisonous products of the bacillus. 



The To.xiiics of Dipiitheria. 



Martin found that after the poison formed in the throat has 

 made its way into the internal organs of the body it undergoes 

 certain changes ; it is broken down into somewhat less poisonous 

 compounds, but these, accumulating at certain points, act especi- 

 ally on the nerves and muscles. It appears then that we have to 

 deal with two sets of poisons : a very virulent poison formed by 

 the bacilli directly from the fibrin and albuminoids of the fiuids of 

 the blood, exuded on the surface of the mucous membrane ; and 

 secondly, a less poisonous series which appear to accumulate 

 especially in Ihe spleen. So long as these poisons remain in 

 the body we have the general fever, rise of temperature, and 

 altered conditions of circulation (as evidenced by the pulse), so 

 characteristic of the disease. At a later stage, sometimes after all 

 the primary symptoms of diphtheria have p.assed away, there 

 are often met with what are called post-diphiheriiic paralyses, 

 which are due apparently to alierations in the nerves going to 

 muscles, especially those going to the delicate muscles of the soft 

 palate and around the opening into Ihe windpipe, though other 

 groups of nerves and muscles may be similarly affected. These 

 post-diphiheriiic paralyses may be due then to the action either 

 of the virulent poison (ferment) formed in the membrane, or of 

 the .somewhat less puisonous but more stable toxines that are 

 formed in the later stages of the disease. Through the kind- 

 ness of Dr. Martin I am enabled to show you figures of nerves 

 and muscles, the degeneration of which is due to the action of 

 these poisonous substances. It is here unnecessary to enter 

 into any detail as to the minute changes that take place in the 

 nerve and muscle fibres, but on comparison of the aflected 

 nerve fibres with a healthy nerve fibre, it is evident ihat we have 

 here grave struciural alterations which must interfere most ma- 

 terially with the pciwer of the nerve to conduct nerve impres- 

 sions from the spinal cord to the muscle. The outer part orsheaih 

 of the neive is in some places entirely wanting, whilst in other 

 cases the axis cylinder or core of the nerve is either greatly at- 

 tenuated or entirely absent. The prison in these cases has set up 

 changes by which the communicating paihs between the muscles 

 and the spinal cord and brain have become ihoroughly dis- I 

 organised. The muscles, too, instead of being formed of cleanly 



NO. 132 I, VOL. 5 l] 



striated fibres, have this striation greatly obscured, first by a kind 

 of cloudy or ground-glass look, and later by the appearance of 

 a number of -trongly refractilc granules. These, when stained 

 with osmic acid, become black, from which we argue that they 

 are composed of fat, and it is said that the muscle has under- 

 gone a fatty degenerttion, the muscuUr protoplasm being 

 partially converted into fat ; nbimately the striatinn may 

 be almost lost. In a case of diphtheria, then, the following 

 stages may be traced: a sore throat (often simple enough 

 to begin with), by which the mucous membrane is prepared for 

 the receptii II of the diphtheria bacillus. The diphtheria bacillus 

 becomes implanted on this surface, gives rise to an acute in- 

 liammatory condition, and, subsisting on the inflammatory 

 exuHalion, sets up a local manufactory of a most virulent poison. 

 This poison, absorbed into the circulation, at once acts on the 

 nervous system, although a certa'n proponion seems to be 

 broken down into more stable, but less virulent, poison, which 

 remains in the body, and may continue to act for a considerable 

 time on the nerves and muscles. 



Immunity against Diphtheria. 



Whilst these poisons are attacking the more highly 

 organised, and therefore less stable tissues, they are stir- 

 ring up or stimulating the other tissues of the body to resist 

 their invasion and action. If tnis were not the case, 

 any one attacked by diphtheria must eventually succumb 

 to the disease ; but we know a considerable proportion of 

 the cases of diphtheria recover even when no treatment at all 

 is resoried to. Whatever may be the exact explanation of this 

 recovery, we know that it depends upon the power of certain 

 cells in the body to accommodate them-elves to the presence of 

 ' the toxines, and to go on doing their work of scavengering and 

 of removing foreign substances from the body even under what 

 originally were adverse condition-. ; during this process the cells 

 become so profoundly and permanently altered that the patient 

 is for some time protected against further attacks of the same 

 disease. It was originally maintained that this alter- 

 ation was entirely conlined to the cells, but it is now gener- 

 ally accepud that these cells form or secrete substances which, 

 thrown into ihe blood, either act direcily upon the toxines so as 

 to interfere with their activity, or so react upon the cells that 

 they are able to coniinue their work in the presence of the 

 toxine. At all events, a certain immunity against the disease is 

 acquired. Upon these various theories is based the rationale of 

 the antitoxic serum treatment of diphtheria. Ferran claims to 

 have been the first to obtain such a condition of immunity 

 against diphtheria in animals: shortly afterwards, Fr.aenkel 

 in Germany obtained similar results. Seeing that this 

 immunity depends upon an alteration in the composition 

 of the serum, should it not be possible, argued Prof. Eehring, 

 to take the serum of an immunised animal and transfer 

 it to a patient suffering from diphtheria, so as to help the 

 tissues and cells of the patient to cope with the toxic products 

 of the diphtheria bacillus during the earlier stages of the dis- 

 ease, inducing, .as it were, a kind of artificial immunity to help 

 the patient over the acute period of the attack when the poisons, 

 though most virulent, are most unstable, and when the tissues 

 have not yet become ;icclimatised to the presence of the toxic 

 products of the bacillus ; when, in fact, they are paralysed and 

 are able to do little to protei t themselves. Behring so followed 

 up this idea, that he was able to initiate a system of treatment 

 which promises to revolutionise our therapeutic methods in the 

 treatment of certain specific infective diseases. 



I'hc Production of Antitoxic Serum. 

 Workingon the fact that an animal might be rendered more and 

 more insusceptible to the action of the toxic products of bacteria, 

 Behring found that he might proceed in either of two ways. 

 He mi^'ht make an artificial wound with a nee ilc, anil introduce 

 weakened bacilli into the animal, the weakened bacilli then 

 growing but feebly and producing a modified toxine. After 

 the effects of ihe first dose h.id passed otT, he was enabled to 

 increase the dose and to use more active bacilli, injecting them 

 first into the tissues and eventually directly into the circulation, 

 with the result that enormous doses of virulent diphtheria bacilli 

 might ultimately be introduced without giving rise to more 

 local swelling or general febrile disturb.ince than was first 

 noticed when the small dose of modified bacilli was introduced. 

 Such a method as this, however, was attended with con- 

 siderable drawb.acks, as it was almost impossible to gauge, at 



