^9 VIRUSES AND HUMAN VffiLPARE 



diseased patients to healthy patients by means of the mosquito vector, Aedes 

 aegypti. ihe earliest method of control of yellow fever involved simply the 

 destruction of the mosquito. Since this insect is one v/hich breeds near the 

 habitation of man, it proved to be not too difficult a problem to eradicate it 

 In populous areas where epidemic yellow fever hitherto had been prevalent. Thus 

 yellow fever as an epidemic was conquered. Hov/ever, yellov/ fever was not eradi- 

 cated by this approach. Gradually the realization grew upon medical scholars 

 that yellow fever still persists in the jungles and that occasionally men ex- 

 posed to the jungle habitat become infected. Thus it became necessary to find 

 some other means of combating the danger of yellov; fever for those individuals 

 who are required to spend time in the jungles of tropical regions. Clearly, in- 

 sect control was not the answer, for it is impossible to eradicate all the possi- 

 ble insect vectors in a jungle. Progress toward the solution of the yellow fever 

 problem was realized when it was first found possible to develop the disease in 

 experimental animals. The disease was first transferred to the rhesus monkey in 

 1927 by Stokes, bauer and Hudson, and later - in 1930 - i't was shown by 'rheiler 

 that it could be passed to the mouse by intracerebral inoculation. Later the 

 virus was propagated in tissue culture and finally by Elmendorf and Smith in 

 chicken embryos. Numerous attempts were made to attenuate the virus by success- 

 ive passages through mouse brain and other materials, finally rheiler and as- 

 sociates developed a strain of yellow fever virus now known as 17D. This strain 

 was obtained by serial passage in chicken embryo tissue culture from which the 

 central nervous system was removed. It turned out to have the remarkable pro- 

 perty of producing an extremely mild infection in man which nevertheless confers 

 complete immunity against yellow fever. Thus today a live vaccine is available 

 for use against yellow fever. Millions of people have been vaccinated by 17D. 

 The success of our armed forces in jungle regions must be attributed in large 

 part to the immunity to jungle yellow fever derived from this one vaccine. At- 

 tempts have been made by Theiler to reproduce the development of a strain of 

 yellow fever similar to 1713. Thus far they have been without success. This de- 

 velopment can be considered as a laboratory accident. Nevertheless it has pro- 

 vided a completely acceptable means of protecting against yellow fever for those 

 in the jungles. 



Other virus diseases have yielded to a similar experimental approach. One 

 of the most recent is dengue. This is a serious tropical regions disease which 

 causes a severe rash in the individual and a total disability for the duration 

 of the attack. During the war, the Dengue Commission of the U.S. Army gathered 

 dengue virus from many theatres of the war both in the Mediterranean and the 

 Pacific areas. Large scale experiments were carried out with human volunteers 

 in this country by Sabin and Schlesinger, at that time of the Army Medical Corps. 

 Human volunteers were used for perpetuation of the virus and for test subjects 

 to determine the success or failure of attempts to grow the virus in experimental 

 animals. Eventually Sabin and Schlesinger were able to get the virus to infect 

 a particular strain of white mice. They achieved success only after they first 

 used the physical method of ultracentrifugation to concentrate the virus and thus 

 provide a high concentration level. This was passed through many generations of 

 mice, and eventually a strain was isolated which has the remarkable property of 

 producing only the skin rash characteristic of dengue. The fever and general 

 disability associated with the virus are not produced. Antibodies to the viru- 

 lent form are induced. This live virus can be used as a vaccine to protect troops 

 who must enter areas where dengue is prevalent. Its development virtually co- 

 incided with the end of the war. Thus far, no satisfactory test of its effect- 

 iveness has been realized. However, there is every reason to believe that dengue 

 vaccine will prove an effective prophylactic agent against the ravages of dengue. 



Influenza is another of the virus diseases to have gone dov/n in defeat be- 

 fore the forces of science during the late war experience. Influenza has been 

 a serious source of death at various times during the past. It is not probable 

 that the high death toll experienced during the pandemic of I918-I9 will ever 



