324 



NATURE 



[August 4, 1898 



3ust indicated, the whole of the proteids, and together 

 with them all antitoxic virtue, is absent from the filtrate. 

 Toxin, on the other hand, the molecular size of which is 

 of the albumose order, is not held back by the filter. 

 Corresponding results are obtained with the toxin and 

 antitoxin of snake venom. 



Coming now to the second question, the nature of the 

 antagonism between these substances, we find that it is 

 one on which a difference of opinion has hitherto been 

 held. Behring, Ehrlich, Kanthack and Brodie maintain 

 that the antagonism is of a chemical nature, and that the 

 antitoxin neutralises the toxin much in the same way 

 that an alkali neutralises an acid. Buchner, Calmette, 

 Metchnikofif, and others, on the other hand, regard the 

 action as an indirect one, operating in some way through 

 the medium of the cells of the organism. The work on 

 which such an assertion rests may be instanced by a 

 typical experiment of Calmette's on ccbra poison. The 

 venom is not attenuated by heating its solutions to 

 •68" C. for ten minutes ; the antitoxin is, however, com- 

 pletely destroyed by this treatment. Mixtures of cobra 

 toxin and antitoxin, which produced no symptoms when 

 injected into rabbits, killed similar rabbits in a few hours 

 if, after the mixture had remained in contact for ten 

 minutes, it were heated to 68' C. for another ten minutes 

 before injecting ; hence the conclusion that the toxin and 

 antitoxin do not interact in vitro, but only in corpore, 

 and therefore that the action cannot be explained as a 

 simple chemical operation between the two. 



Such an experiment is not, however, conclusive ; it can 

 be easily repeated with the same result, but the source of 

 fallacy is that it takes no account of the factor — time. 

 Every chemical operation has a certain definite velocity 

 coefficient, and the rapidity of action under any circum- 

 stances when the reacting compounds are in solution 

 depends upon this coefficient, and also upon the pro- 

 duct of the active masses of the compounds present. 

 Temperature will also exercise an important influence. 



Remembering the high molecular weight of both toxin 

 and antitoxin, one would a priori expect the velocity 

 •coefficient of any reaction between them to be a high 

 one, and in addition the solution would contain relatively 

 few molecules ; so it is not surprising that any chemical 

 operation should occupy a very appreciable time. If 

 the two substances are left in contact for more than 

 •Calmette's ten minutes, the substances completely 

 neutralise each other in vitro. 



The following table gives a summary of Martin and 



other, with proportion of active masses constant. On 

 reading any vertical line, the influence of varying propor- 

 tions of active masses with time of operation constant is 

 indicated. The thick line separates ofif the fatal results 

 from those in which the rabbits lived. All other factors 

 were kept constant. The solutions were mixed in the 

 varying proportions, and stood at laboratory tempera- 

 ture (20°-23° C). At stated intervals, by a stop-watch, 

 portions were pipetted off, and the reaction terminated 

 by rapidly raising the temperature to 68° C. in a water 

 bath. They were kept at this temperature for ten 

 minutes, cooled, and kept for injection. 



Exactly corresponding results were obtained with 

 diphtheria toxin and antitoxin ; and we may conclude 

 by quoting an experiment with these substances, in 

 which a different modus operandi was adopted. Similar 

 experiments have been recently performed by Brodie, 

 and published in his Arris and Gale lectures ; his results 

 completely coincide with those of Martin and Cherry. 



A solution of toxin containing eight fatal doses per 

 kilogram of guinea-pig in each c.c. was mixed with 

 sufficient antitoxin to more than completely neutralise 

 all the toxin. This mixture was allowed to remain in 

 contact at 30° C.for two hours, and then filteied through 

 the gelatin filter. Varying quantities of the filtrate were 

 injected into guinea-pigs up to nearly 4 c.c. per kilogram 

 of body-weight ; that is, a quantity originally containing 

 thirty-two fatal doses. The filtrate was quite innocent. 

 The guinea-pigs suffered no inconvenience, and gained 

 weight while under observation in small cages. The 

 injections produced no local oedema. 



If the toxin had remained unaffected beside the anti- 

 toxin, there was nothing to prevent it passing through the 

 filter in virtue of its relatively small molecular size. As, 

 however, it did not do so, we can only conclude that it 

 had entered into some sort of chemical relationship with 

 the relatively large molecules of the antitoxin during 

 their sojourn together prior to filtration. 



W. D. H. 



A MINISTER OF EDUCATION AT LAST. 



THE Duke of Devonshire made a most important 

 speech on Monday in introducing a new Bill relating 

 to Secondary Education. 



The Bill really seeks to reconstruct the whole of our 

 haphazard organisation dealing with Education, Science 

 and Art ; whether the recommendation will do harm or 



Cherry's principal experiments with snake venom. On 

 reading along any horizontal line will be seen the in- 

 fluence upon the result of the time during which the 

 toxin and antitoxin were allowed to operate upon each 



NO. 1 501 VOL. 58] 



good depends upon the reconstructors, and who they are 

 does not appear. It should, however, be a matter of 

 congratulation that the lamentable condition of our 

 present want of system, which has been known to educa- 



