260 



SCIENCE 



[N. S. Vol. XLIV. No. 1130 



such resistant or protected monkeys, and then 

 by Levaditi and Netter, 4 and by Flexner and 

 Lewis in the blood of human beings who had 

 recovered from acute poliomyelitis, of immu- 

 nity substances which possessed the power of 

 neutralizing the virus of poliomyelitis when 

 the serum and the virus were brought together 

 in the test tube. Flexner and Lewis ascer- 

 tained, also, that the serum of monkeys actively 

 immunized 5 with the virus under conditions in 

 which all symptoms of the disease were 

 avoided, contained similar immunity bodies. 



EXPERIMENTAL SERUM THERAPY 



The next step taken was the determination 

 hj Flexner and Lewis that both the immune 

 monkey 6 and the immune human serum 7 which 

 •exhibited the neutralizing power for the virus 

 "possessed also therapeutic properties for 

 monkeys inoculated with the potent virus of 

 poliomyelitis in contradistinction to the 

 normal serum from the same animal sources 

 which was devoid of those properties. 



The experimental demonstration of the 

 therapeutic activity of the immune sera was 

 made in the following manner. Ehesus mon- 

 keys were inoculated (a) intracerebrally and 

 (6) intranasally with a virus which had be- 

 come adapted to the monkey and was highly 

 potent. The effective intracerebral dose of a 

 Berkefeld filtrate of a 5 per cent, emulsion of 

 the spinal cord of an infected monkey was 

 less than 0.01 c.c. Hence the quantity of the 

 filtrate injected into the brain of the ether- 

 ized monkeys varied from 0.01 to 0.1 'c.c. The 

 inoculations were made in the afternoon and 

 the therapeutic treatment was begun the next 

 day, or from eighteen to twenty-four hours 

 Poliomyelitis in Monkeys," seventh note, J. A. M. 

 A., 1910, LIV., 1780. 



i Levaditi and Netter, A., Presse med., 1910, 

 XVIII., 268. Flexner, S., and Lewis, P. A., sev- 

 enth note, loc. cit. 



s Flexner, S., and Lewis, P. A., "Experimental 

 Poliomyelitis in Monkeys," eighth note, J. A. M. 

 A., 1910, LV., 662. 



o Flexner, S., and Lewis, P. A., seventh note, 

 loc. cit. 



t Flexner, S., and Lewis, P. A., eighth note, 

 loc. cit. 



later. When the virus was introduced by the 

 nasal route the filtrate was not employed, but 

 an emulsion of the spinal cord was rubbed 

 upon the upper nasal mucosa. 



The immune sera were applied by intra- 

 spinal or subdural injection. The usual 

 method was to inject from 2 c.c. to 3 c.c. of 

 the immune sera through the lumbar puncture 

 needle daily for several days or daily for three 

 injections followed by an interval of three 

 days when the three injections were repeated. 

 The conclusions reached from these experi- 

 ments were in substance that if the quantity 

 of virus is not in excess of a given dose, the 

 infection can be either wholly prevented or the 

 onset of the paralysis much delayed. In other 

 words when dealing with the virus adapted to 

 the monkey which induces poliomyelitis almost 

 without exception and in which the symptoms 

 are far more severe and the mortality far 

 greater than occur in the disease in human 

 beings, the immune monkey and human sera 

 are capable of preventing in all but a few in- 

 stances the development of the virus even when 

 inoculated intracerebrally, and in the excep- 

 tional instances in which the development is 

 not wholly prevented, the onset of the disease 

 is much delayed. The power, therefore, to 

 neutralize the virus possessed by the immune 

 sera is exercised in vivo under severe experi- 

 mental conditions almost as constantly as in 

 vitro under relatively favorable ones. 



In order that maximal effect of the immune 

 sera may be secured it is necessary that the 

 injections be made into the subdural space 

 which can be readily and safely accomplished 

 by means of lumbar puncture. The reason for 

 this mode of application of the serum depends 

 upon the facts that it is the most direct route 

 to the central nervous tissues and, however 

 the virus' is introduced into the body, it estab- 

 lishes itself in the cerebrospinal meninges. 8 



8 Flexner, S., and Lewis, P. A., seventh note, 

 loc. cit. Flexner, S., "The Contribution of Ex- 

 perimental to Human Poliomyelitis," J. A. M. A., 

 1910, LV., 1105. Flexner, S., and Amos, H. L., 

 "Penetration of the Virus of Poliomyelitis from 

 the Blood into the Cerebrospinal Fluid," Jour. 

 Exper. Med., 1914, XIX., 411. 



