May 17, 19 1 7] 



NATURE 



229 



rats were susceptible to the disease, had excited 

 the curiosity of bacteriologists. With the view 

 of discovering^ the cause of the resistance of white 

 rats, Behring tried the effect of their serum upon 

 anthrax bacilli in vitro, and found that anthrax 

 bacilli were killed by a short sojourn in fresh 

 serum. This observation, together with those of 

 Nuttall upon the similar properties of the fresh 

 serum of man and several animals, formed the 

 foundation of the humoral theory of defence 

 against the invasion of microbes into the animal 

 body. 



In 1888 Behring went to Berlin and became an 

 assistant to Koch at the Hygienic Institute. 

 There he was associated with Loeffler and 

 Kitasato, who had recently discovered the 

 microbes causing diphtheria and tetanus respec- 

 tively, diseases apparently brought about by the 

 local multiplication of the organisms and with- 

 out the penetration of the bacilli into the body 

 generally. These were imp)ortant steps in the 

 interpretation of zymotic disease, and indicated 

 that microbes manufactured soluble p)oisons 

 which, being absorbed, acted upon the cells of 

 the nervous system and other essential organs. 

 The demonstration of the accuracy of this inter- 

 pretation followed in 1888 when Roux and Yersin 

 grew diphtheria bacilli in broth, removed the 

 bacteria by filtration through unglazed porcelain, 

 and produced the characteristic effects of 

 diphtheria with the sterile filtrate. To this 

 bacillary poison they gave the name "toxin." 



Following up his earlier researches, Behring, 

 by rejjeated small inoculations of certain 

 microbes, immunised animals against large doses, 

 and showed that their serum possessed the 

 propert^h' of destroying in vitro, in an enhanced 

 degree, the microbes to which they had been 

 accustomed. 



The psychological moment for the discovery of 

 anti-toxic immunity had now arrived, and in 1890 

 Behring and Kitasato announced the discovery 

 that an animal, immunised against tetanus and 

 diphtheria by graduated injections of killed broth 

 cultures of these rnicrobes, produces in its blood 

 substances which are capable of neutralising the 

 toxic actions of these bacteria. They also showed 

 that an animal previously injected with the serum 

 of such an immunised animal withstood an other- 

 wise fatal dose of bacilli or toxin, and, further, 

 that when treated with the serum, even after 

 symptoms had developed, it could be cured. To 

 the substance in the serum of immunised animals 

 they gave the name "anti-toxin." These funda- 

 mental observations were carried a stage further 

 by Behring and Baer, and the serum tested on 

 children with favourable results. 



The importance of the initial discover}- by 

 Behring and Kitasato was at jonce seized by 

 Emil Roux, the present director of the Pasteur 

 Institute, who, in collaboi*ation with Louis 

 Martin, developed a method for its practical 

 application which has been changed in little else 

 than detail up to the present day. They 

 injmunised horses and were thus able to produce 



NO. 2481, VOL. 99] 



anti-toxic serum in quantity. In collaboration 

 with their colleagues at the Paris hospitals, a 

 trial of the new remedy was made in such a 

 manner and upon such a scale as to place the 

 serum treatment of diphtheria upon a firm basis 

 by 1894. - 



During the last tAvelve years Behring's 

 scientific activity had been for the most part 

 directed to the problems of the immunisation 

 against and cure of tuberculosis in man and 

 animaJs. Behring started with fhree theses. 

 The first is that the bacilli of human and bovine 

 tuberculosis are but varieties of the same 

 organism ; the second is that infection, in the case 

 of both man and animals, takes place in early 

 life via the alimentary canal, and that phthisis 

 is a sequel to such intestinal infection ; and 

 the third is that few humans or bovines escape 

 infection before becoming adult. The first and 

 second of these views, although receiving support 

 in some quarters, have not been generally 

 accepted, and the assertiveness, unsupported by 

 evidence, with which they have been expoimded 

 by their author has not conduced to their receiv- 

 .ing even so much attention as they deserve. 

 Assuming their correctness, however, it is 

 obvious that prophylactic immunisation, if it is 

 to be effective, must be undertaken in early life. 

 Behring attempted this with cattle, using 

 attenuated human tubercle bacilli, but the results 

 were not commensurate with expectations. 



The treatment of children with any form of 

 living tubercle bacilli being impracticable, 

 Behring endeavoured to prepare extracts of killed 

 bacilli which might p>ossess the desired prop>erties. 

 The difficulties of inquiries in this domain, and 

 their possible value to humanity, can scarcely be 

 exaggerated, and it is a matter for regret that 

 Behring's efforts therein should have been 

 shrouded in a certain mysteriousness which is 

 inimical to the best interests of science. A 

 product of tubercle bacilli called " tulase ' ' was 

 evolved, which, according to the author, 

 immunised animals against living tubercle bacilli 

 and was effective in the treatment of tuberculosis 

 in man. The exact nature and methods of 

 preparation of tulase have not been made known 

 beyond the statement that it is produced by the 

 prolonged action t)f chloral hydrate upon tubercle 

 bacilli, and is different from tuberculin. As, 

 however, no results of this remedy have been 

 forthcoming, and as several years have passed 

 since it was introduced, it has presumably proved 

 disappointing. 



From 1895 until shortly before his death 

 Behring was professor of hygiene in the Univer- 

 sity of Marburg, and director of the Hygienic 

 Institute. For his discovery of anti-toxin he was 

 awarded in 1895 the prize of the Academic de 

 Medecine and Institut de France, and he had 

 many distinctions conferred upon him by learned 

 societies. In 1901 he received the patent of 

 nobility, and in the same year was awarded the 

 Xobel prize. 



C. J. M. 



