SCIENCE 



[Vol. XVII. No. 413 



pyocyaneus for rabbits. He made the animals immune by 

 injections of sterilized culture-fluids, and found that serum 

 from such animals exerted a far greater " bactericidal " action 

 on the microbe in question than serum from a normal animal. 

 Behring- and Nissen/ in a paper published in May of this 

 year, went a step further. They showed, that, whereas 

 blood-serum from an animal made immune against anthrax 

 exerted an increased bactericidal action on the anthrax bacil- 

 lus, it showed no increased action on the bacillus pyocyaneus. 

 Conversely blood sei-um from an animal made immune 

 against the latter microbe had no increased action on the 

 anthrax bacillus, though it exerted a powej'ful bacteria-killing 

 action on pyocyaneus. The authors considered that they 

 had proved the existence of two bodies, each having a speciflc 

 action on one of the two microbes in question, and, further, 

 that these substances are present in animals made immune 

 against the above-named diseases. These remarkable con- 

 clusions acquire a still greater interest when received in the 

 light of a research by-Gamaleia published at the beginning 

 of last year." Gamaleia found that the aqueous humor of 

 a sheep, about three days after inoculation with attenuated 

 anthrax, acquires bactericidal properties for this microbe. 

 This condition lasts for nearly a month, and then gradually 

 vanishes, though, as is well known, the sheep remains im- 

 mune for a far longer period. These researches therefore 

 suggest, first, that, when an animal has been made immune 

 against a pathogenic microbe, its blood and other body fluids 

 contain a substance capable of destroying the microbe in 

 question: second, it follows that such protective substinces 

 can remain in the body undestroyed for a considerable time; 

 and, third, that they can be present in such quantities as to 

 be able to kill the microbes involved (even without the help 

 of living cells) and yet produce no appreciable ill efFect on 

 the general health of the animal. If this is so, why should 

 it not be possible to cure any infectious disease by injecting 

 a "lymph" obtained from the blood or tissues of an animal 

 previously made refractory to the disease in question ? 



Whether or not the above considerations stimulated the 

 I'esearches of Behring and Kitasato, their work affords a 

 positive answer to this question, which promises to be of the 

 greatest importance to humanity, and has led them to the 

 most unexpected and interesting results from the scientific 

 standpoint. The following is a summary of their paper, 

 which is of the nature of a preliminary communication.'' The 

 method by which, in the first case, they produced immunity 

 against tetanus and diphtheria, is not described. Only so 

 much of their results is communicated as is necessary to sup- 

 port the following propositions: — 



" The immunity of rabbits and mice against tetanus de- 

 pends on the power possessed by the fluid part of their blood 

 of rendering harmless the poisonous substances produced by 

 the tetanus bacilli." 



This proposition involves a completely new theory of the 

 nature of acquired immunity. Hitherto it has been thought 

 that immunity must depend either on the voracious activity 

 of phagocytes, or on the above-mentioned bacteria-killing 

 power of the blood, or on an acquired tolerance against a 

 poison; and, further, that by the method of residiies any 

 one of these theories could be proved by showing the other 

 two to be false. 



Behring, however, was able to prove, by his work on diph- 



^ " tjeber den batterienfeindllchen Elnfluss von verschledenen Serumar- 

 ten " (Zeitschrltt (fir Hygiene, vol. vlli. p. 412). 



- " Sur la destruction des microbes dans ies corps des animaux febrlci- 

 tants "(Annates de V Institut Pasteur, 1889, p. 229). 



2 A fuller account will shortly appear In tlie Zeltschrlft fiir Hygiene. 



theria, that none of these theories would account for the 

 natural immunity of rats or the artificially produced immu- 

 nity of guinea-pigs against this disease. After disproving- 

 many speculations on this subject, the above given explana- 

 tion was arrived at, but they only obtained a satisfactory 

 jjroof of its correctness when they began to test it on the 

 tetanus microbe. 



Their experiments prove, — 



(1) That the blood of rabbits which have been made im- 

 mune against tetanus can destroy the tetanus poison. 



(2) This character can be shown to be possessed by the 

 blood both before and after it has left the vessels, and in the 

 cell-free blood-serum obtained from it. 



(3) This character is of so permanent a nature that it is 

 still manifested by such serum after it has been injected 

 into other animals: consequently, by transfusion of such 

 blood or serum, important therapeutic actions can be ob- 

 tained. 



(4) This power of destroying the tetanus poison is absent 

 from the blood of such animals as are not immune against 

 tetanus; and, after such animals have been killed by the 

 tetanus poison, it can be shown to be present in their blood 

 and tissues. 



In support of these assertions the following experimental 

 results are brought forward. 



A rabbit was made immune against tetanus by a method 

 which will be described in a forthcoming paper by Kitasato 

 in the Zeitschrift fiir Hygiene. To prove the completeness 

 of its immunity, 10 cubic centimetres of a virulent culture 

 was injected into it. Half a cubic centimetre of the same 

 culture was quite sufficient to produce tetanus in a normal 

 rabbit. The treated rabbit, however, remained immune, and 

 it showed immunity not only against the tetanus bacillus, 

 but also against the poison produced by this microbe, for it 

 remained unharmed by an injection of twenty times the 

 quantity of tetanus poison which will kill with certainty a 

 normal rabbit. Blood was taken from the carotid artery of 

 this rabbit. Before clotting occurred .2 of a cubic centi- 

 metre of this blood was injected into the body-cavity of a 

 mouse, and .5 of a cubic centimetre into that of another. 

 Twenty-four hours later, these mice, together with two con- 

 trol-mice, were inoculated with tetanus of such virulence 

 that the latter showed the symptoms of tetanus after twenty 

 hours, and were dead in thirty-six hours. Both of the 

 treated mice, on the contrary, remained healthy. 



The greater quantity of the blood of this rabbit was 

 allowed to stand, and its serum collected. 



Six mice each received 2 cubic centimetres of this serum in 

 the abdominal cavity, and all withstood a subsequent inocu- 

 lation with tetanus. Control-mice died of tetanus within 

 forty eight hours. 



With this serum the authors succeeded in curing animals 

 that had been previously infected with tetanus. They have 

 also been able to show that this serum possesses an intense 

 power of destroying the tetanus-poison. 



Of a ten-days-old tetanus culture which had been steril- 

 ized by filtering, .00005 of a cubic centimetre was enough to 

 kill a mouse after four to six days, and .0001 would always 

 produce the same result in less than two days. 



Five cubic centimetres of the serum of a tetanus-immune 

 rabbit was mixed with 1 cubic centimetre of this filtered cul- 

 ture, and kept for twenty-four hours. Of this mixture, four 

 mice each received .2 of a cubic centimetre (that is to say, 

 .033 of the original culture, or more than 300 times the quan- 

 tity which would otherwise be capable of killing a mouse). 



