650 FILTERABLE VIRUSES— RICKETTSIA 
indeed rabid dogs frequently swim across streams that they happen 
*to encounter. The final stage of rabies is a progressive paralysis, 
which usually first becomes manifest in the limbs and arms; it ascends 
gradually and death occurs when the higher centers are reached. 
The disease occurs in every country except England, and possibly 
Australia. The elimination of rabies from England dates from the 
law of 1889 which required all dogs to be muzzled and all imported 
animals to be quarantined for several months. The law was allowed 
to lapse for a time, the disease reappeared, but a new and rigid enforce- 
ment of the muzzling and quarantine laws has completely eliminated 
rabies from the British Isles. Xo cases were reported there between 
1903 and the outbreak of the World War. 
The first definite lesions characteristic of rabies were described 
by Negri, ^ who found characteristic cell inclusion bodies in the ganglion 
cells, in the cells of Purkinje, and other large nerve cells. These minute 
granular pleomorphic bodies are now recognized as specific, or nearly 
so, for hydrophobia, but there is discussion of their nature. Williams- 
regards them as protozoa and conferred upon them the name Xeuror- 
rhyctes hydrophobiae ; in collaboration with Lowden^ she has made a 
careful study of the occurrence of Negri bodies and considers them the 
true etiological agent of rabies. Remlinger,^ Poor and Steinhardt,'* 
and others have found that the virus is filterable, and Noguchi*' has 
cultivated an organism from "street" virus and from the central 
nervous system of animals infected with "street" virus, "fixed" virus 
and with "passage" virus, which resembles Negri bodies observed in 
lesions in many particulars. The smallest of these bodies are just 
visible with the highest magnifications obtainable; larger nucleated 
or oval bodies occasionally appear in older cultures. Inoculation of 
dogs, rabbits and guinea-pigs with cultures containing the granular 
pleomorphic or nucleated bodies was followed by typical symptoms 
of rabies. The relation of the organisms grown by Noguchi to Negri 
bodies is not definitely determined as yet, but the virus has been 
kept alive for over three months in artificial cultures and found to 
be virulent after the twenty-first transfer in artificial media. This 
would suggest that Noguchi's organism was the etiological agent of 
rabies. The possibility that a filterable virus was growing in these 
cultures cannot be overlooked, as Noguchi has pointed out, but there 
is no evidence that such is the case. 
The most important rapid laboratory method for the diagnosis of 
rabies is a demonstration of Negri bodies. If they are found the 
diagnosis is complete. Failure to find them does not necessarily 
exclude a diagnosis of rabies, and an emulsion prepared from the 
1 Ztschr. f. Hyg., 1903, 43, 507; 1909, 63, 421. 
2 Proc. New York Path. Soc, 1906, 6, 77. 
' Williams and Lowden: Jour. Infec. Dis., 1906, 3, 452. 
* Ann. Inst. Pasteur, 1903, 17, 834; 1904, 18, 150. 
5 Jour. Infec. Dis., 1913, 12, 202. 
« Jour. Exp. Med., 1913, 18, 314. 
