EXPERIMENTS WITH POLIOMYELITIS IN THE RABBIT.
The poliomyelitic virus obtained from an experimental monkey has been passed through eight generations in rabbits. It shows no signs of dying out. On the other hand, it gives no evidence of becoming more pathogenic to the species through successive passage. The period of incubation remains variable and the percentage of takes has not increased. Whether eventually a virus can be obtained which is of heightened virulence to rabbits is problematic. All inoculations are by no means successful. The animals show great individual differences in susceptibility to the virus, as is evidenced by the fact that out of fifty-four rabbits inoculated, only twenty-two, or about 40 per cent, succumbed. This fact may explain the negative results of other investigators. At several points in the series of experiments it was thought that the strain had died out. As many as six rabbits have been inoculated one after the other before the virus would catch again. The age of the rabbits is important in considering the susceptibility. From the limited data at our command, adult rabbits are resistant, and there appears to be an abrupt increase in resistance between the age of 6 and 8 weeks; that is, rabbits under 6 weeks are more susceptible to the virus. There seems to be a parallel between the age incidence of this disease in rabbits and spontaneous poliomyelitis in man. The age incidence of poliomyelitis in man is indicated by the term "infantile paralysis." Several methods of inoculation have proved successful; thus the rabbits have succumbed as a result of introducing the virus directly into the brain, by injecting it into a peripheral nerve, or directly into the circulation, or by placing it upon the uninjured nasal mucosa. The symptoms produced show more or less departure from the symptoms of poliomyelitis as seen in the spontaneous disease in man and in the experimental disease in the monkey. There are two distinct pictures recognizable. In one there is paralysis of one or more of the extremities which progresses until death, resembling somewhat the symptoms of the experimental disease in the monkey. This we have designated the progressive type. The other group is included in what we have called the fulminating type. The symptoms are explosive in character, with extreme weakness amounting to prostration, terminating in death in a few hours, attendant upon respiratory failure. The mode of inoculation seems to have little effect upon the type of symptoms produced. The period of incubation is variable and apparently does not depend upon the method of inoculation. The period varied from 2 to 41 days, with an average of 12 days. The two extremes both occurred after intracranial injection. After intranasal insufflation the incubation period was short, being in each case 2 days, followed by symptoms of the fulminating type. The placing of the virus into the nose seems to be an effective method, but is as uncertain as other routes, as only three out of nine rabbits tested in this manner succumbed. The disease produced by this route was particularly virulent. The virus shows no tendency to become fixed. The period of incubation is as variable in the eighth generation as in the first, and the virus has shown no tendency towards increasing virulence through successive passage, in these respects differing from the virus of rabies. We have found the virus to be filterable. An emulsion of the central nervous matter of a rabbit of the first generation passed through a Berkefeld filter, and injected intracerebrally into another rabbit, resulted in death, preceded by symptoms of the fulminating type. Virus (unfiltered) from this rabbit was transferred successfully to two other rabbits. The lesions, while definite and consistent throughout the series, lack the distinctive features of the pathologic picture of poliomyelitis in man and the monkey. Capillary congestion, punctate hemorrhages, degeneration of the motor cells, satellitosis, and more or less cellular infiltration of the gray matter of the cord and medulla are found, but perivascular infiltration is absent and the infiltrating cells are not lymphocytic in character. One of the most striking features of this investigation is the way in which rabbits and monkeys react to the same virus. The disease in the rabbit presents certain clinical resemblances to the experimental disease in the monkey and also to the spontaneous disease in children. On the other hand, the symptoms show marked variation from those seen in the monkey and in man. The picture has not the same constancy in rabbits and could not in most cases be recognized clinically as poliomyelitis. There are still more marked differences in the pathology. While it is true that the brunt of the attack in the rabbit falls upon the gray matter of the cord and medulla, the appearance of the lesions under the microscope shows such differences from the lesions of experimental poliomyelitis in monkeys, as well as the natural disease in man, as to suggest two distinct infections. It is more reasonable, however, to assume that we are dealing with a modified form of poliomyelitis; that the rabbit reacts differently to the virus than the monkey or man; and that the disease produced in rabbits by us and others is in fact poliomyelitis. So far as we know, no other virus produces such differences in two animal species. Smallpox is so profoundly altered in the cow that it took almost 100 years to prove Jenner's assumption that cowpox is a modified form of smallpox. However, the pock of vaccinia is a correct counterpart both clinically and pathologically of the pock of variola. If the virus of poliomyelitis may be so altered in the rabbit as scarcely to be recognizable, may it not be still more profoundly changed in other animals? The conjecture then arises that poliomyelitis, instead of being limited naturally to man and experimentally to monkeys, may in fact occur in other animals in unnoticed or unrecognized form. If this should prove true, it may be a source of human infection and may help to solve the problem of prevention.
Department of Preventive Medicine and Hygiene, Harvard Medical School, Boston.
M J
MJ
Rosenau
L C
LC
Havens