August 14, 1913] 



NATURE 



025 



in the parasites. For instance, it is useless to com- 

 bine euchsin with its nearest relative, methylviolet ; 

 and it is useless to combine therapeutically trypane blue 

 and trypane red, for both attack the same spots in the 

 parasites, but it is necessary to select from each group 

 the most effective substance and then to combine the 

 most suitable representatives of the various types. It 

 is clear that in this manner a simultaneous and varied 

 attack is directed on the parasites, in accordance with 

 the military maxim, " March apart but fight com- 

 bined." 



Combined therapy will in the future conquer an 

 ever-increasing" field of action. Thus, for instance, 

 Broden, in the Congo, succeeded in connection with 

 sleeping sickness in the human subject — it is true only 

 in the early stage of this infection, which is so difficult 

 to fight against — in obtaining good results by the com- 

 bination of salvarsan and two basic colouring matters 

 (trypallavin and tryparosan) by treatment lasting about 

 a wee k. 



It is precisely in the manifold character of the pos- 

 sibilities of combination that I see a special advantage, 

 and peculiar possibilities of development. When once 

 we are acquainted with the majority of the chemo- 

 receptors of a particular kind of parasite, which will 

 be a long piece of work, occupying many hands and 

 heads, we shall have the most far-reaching possibili- 

 ties of simultaneous attack by various agencies. And 

 on this account combination therapeutics are also 

 absolutely pluralistic in contrast to antitoxins, which 

 may be said to act rather in one single direction. 



And now, gentlemen, may I be permitted to refer 

 to a few practical results? You are all aware that 

 with a number of spirillar diseases the principle of 

 therapia sterilisans magna has proved most success- 

 ful. You are aware that it is possible by one single 

 injection of salvarsan to cure frambcesia (yaws), which 

 is also caused by spirochaetes, and is a scourge of 

 the tropics, curing it completely except in rare cases 

 where unimportant relapses occur ; this has been 

 shown by the work of Strong, Koch, and Castellani. 

 Thus, in Surinam, a hospital in which more than 

 300 patients with frambcesia were constantly under 

 treatment was closed and turned to other uses after 

 the introduction of the salvarsan treatment, as one 

 single injection sufficed to cure the disease, and the 

 patients could all be discharged but two. It is to be 

 hoped that in this way it will be possible altogether to 

 extirpate frambcesia. 



Exactly the same favourable results have been 

 attained with recurring fever in the human subject, 

 the fever immediately subsidising after the injection 

 of salvarsan, and the patients being cured by one 

 injection. The very rare cases of relapse occasionally 

 occurring are also readily curable. 



To continue dealing with salvarsan, in syphilis, 

 which is so closely related to frambcesia, a fair per- 

 centage of cures has been obtained in the very first 

 stage of the disease by a single injection of a large 

 dose, but, of course, the abortive cure by intensive 

 treatment is far more certain. 



\Yith Vincent's angina and the diseases of the 

 mucous membrane of the mouth, which are caused 

 bv spirochetes of the mouth, therapia sterilisans 

 magna is possible ; in fact, in many cases a mere 

 local application of salvarsan suffices. I may here 

 further mention tertian malaria, in which form, but 

 in this form alone, salvarsan has proved successful, 

 and blastomycosis (Petersen) and the Aleppo boil. 

 As regards diseases of animals which can be cured 

 by one single injection of salvarsan, I might specially 

 mention breast disease of horses, which is of such 

 enormous importance to the military authorities, and 

 lymphangitis epizootica, the African glanders in 

 horses. 



NO. 2285, VOL. 91] 



Most important are the recent observations of 

 Rogers, who found emetin to be a specific against the 

 very serious amoebic dysentery. And if here it is 

 indeed advisable and necessary to repeat the injections, 

 yet the triumph of therapeutics remains unassailed ; 

 it is all one to the patient as to whether therapia 

 sterilisans or sterilisans fractionata is employed, pro- 

 vided only he is relieved of his sufferings in a harm- 

 less manner. 



Piroplasmosis also, which exerts a disastrous action, 

 causing serious diseases in cattle and dogs, may, 

 according to the observations of Nuttall, be favourably 

 influenced by a pigment belonging to the class of 

 trypane colouring matters, viz. by trypane blue, which 

 was first composed by Mesnil. As I am informed, the 

 fight against this disease has been taken up in a 

 general manner at Pretoria under the auspices of 

 Theiler. The injections are there performed, not by 

 veterinary surgeons, but by the farmers themselves, 

 and they are glad to save their valuable animals scot- 

 free from this serious disease. 



It is indeed easy to understand that the schizo- 

 mycetes, which in themselves are so much hardier than 

 the tender protozoa and spirochaetes, will offer an 

 increased resistance to the attack of drugs. Naturally 

 here, too, there are fine differences, and it is perhaps 

 no accident that the pneumococcus, the protoplasm of 

 which is, of course, most sensitive, should in the 

 course of treatment also have shown itself to be par- 

 ticularly sensitive. (I refer here to the fine researches 

 of Morgenroth in the treatment of laboratory animals 

 infected with the pneumococcus by means of deriva- 

 tives of quinine, especially ethylhydrocuprin.) But in 

 the case of hardier bacteria, too, such as the Bacillus 

 typhosus, the possibility of sterilisation is not beyond 

 hope. The first successful experiments in this sphere 

 were carried out by Conrad on rabbits, and later 

 confirmed and extended by Uhlenhuth and his fellow- 

 workers on this species of animal. 



If I briefly allude to the very hopeful experiments 

 of Grafin Linden, who has endeavoured to influence 

 tuberculous infections favourably by means of combina- 

 tions of copper and lecithin, and if I add that salvar- 

 san also has been shown to have a beneficial action 

 upon the malignant anthrax-bacillus, and upon that 

 of glanders, and, possibly, upon that of erysipelas, 

 both in animal experiments and occasionally, too, in 

 human cases, then all that we know about the chemio- 

 therapeutics of the specific bacterial diseases has been 

 told, so that it is just in this direction that there lies 

 a wide field still to be worked. This field, important 

 as it is, is still in the very first stages of experimenta- 

 tion. 



And if after what has been said we cast a glance 

 over the development of medicine and especially of the 

 fight against infectious diseases, we must recognise 

 that in the last fifty years the most important ad- 

 vances have been made in every direction, advances 

 connected above all with the names of Pasteur, 

 Robert Koch, and von Behring. 



On one hand we have the isolation of the patho- 

 genic bacteria, which was made possible really by the 

 Koch method of the solid culture medium, and in 

 which Robert Koch's pupils and fellow-workers, 

 Loffier, Gafftey, Pfeiffer, in the first order, partici- 

 pated ; the study of protozoa, which started from 

 Laveran's discovery of the germ of malaria; the dis- 

 covery by Loffier and Frosch, Roux and Nocard, of 

 the viruses which pass through filters ; and the recog- 

 nition of insects as intermediate hosts and transmitters 

 of infectious diseases, which is connected with the 

 name of Theobald Smith, and has led to the most 

 important consequences. 



On the other hand we have the study of the im- 

 munitv theorv which was first inaugurated so bril- 



