野口英世著

Journal of Experimental Medicine

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CONTRIBUTION TO THE CULTIVATION
PARASITE OF RABIES.*

OF THEBY H I D E Y O N O G U C H I , M.D.

(From ~,~e Laboratories of The Rockefeller Institute for Medical Research,New York.)
PLATE I9.

Galtier 1 and Pasteur 2 demonstrated the infectiousness of rabies.
Negri ~ next described the characteristic inclusions in the ganglion
cells, and Babes, 4 J. Koch, 5 Volpino, 6 Proescher, 7 and others foundminute granular or pleomorphic particles in the central nervous
system of animals infected with ra~bies. Remlinger, s Poor andSt einhardt, 9 Bertarelli and Volpino ~° demonstrated the filterabilityof the rabic virus; but the nature of the virus itself had remained
unknown.

In the early part of I912 I undertook to cultivate the rabicvirus and I have now obtained certain results regarding whicha brief report is appended. About fifty series of cultivations
were made with the .brain or medulla removed aseptically fromrabbits, guinea pigs, and dogs infected with "street" virus, "passa g e " virus, or " f i x e d " virus. Usually the animals were etherizedjust before spontaneous death occurred.
The method that has yielded the result to be reported is similar
to that employed successfully for the cultivation of the spiroch~et~e* Received for publication, August I, I913.
1 Galtier, Compt. rend. dcad. d. sc., I879, lxxxix, 444.
-~Pasteur, L., Chamberland, and Roux, Compt. rend. dead. d. sc., I88r, xeli, I59.
3 Negri, A., Ztsehri f. Hyg., I9o3, xliii, 507; xliv, 520; I9o9, lxiii, 42I.
Babes, V., Trait~ de la rage, Paris, i912 ; Ztschr. f. Hyg., I9O7, lvi, 435.
5 Koch, J., Ztschr. f. Hyg., Igm, lxvi, 443.
6 Volpino, G., drch. per le sc. reed., I9O4, xxviii, I53.
7 Proescher, F., Berl. klin. Wchnschr., I913, I, 633.
s Remlinger, M. P., .4nn. de l~Inst. Pasteur, ~9o3, xvli, 834; I9O4, xviii, I5o.
9 Poor, D. W., and Steinhardt, E., Jour. Infect. Dis., I913, xii, 202.
10 Bertarelli, E., and Volpino, G., Centralbl. ~. Bakteriol., 4te dbt., Orig,,
I9O4, xxxvii, 5I; Bertarelli, E., idem, IC)O5, xxxix, 399.

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Hideyo Noguchi.

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of relapsing fever) 1 In the cultures very minute granular andsomewhat coarser pleomorphic chromatoid bodies arise which on
subsequent transplantation reappear in the new cultures throughmany generations. The same bodies, so far as appearances areconcerned, are obtained from "street," "passage," and "fixed"
virus. The smallest of these bodies are just on the limit ofVisibility with Zeiss apochromatic 2 millimeter lens. On four
different occasions I observed in the cultures from "passage" and"fixed" virus nucleated round or oval bodies surrounded with membranes totally different from the minuter granular bodies althougharising in the cultures in which the latter occurred. Their appearance was sudden and their duration four to five days, when theydiminished coincident with an increase in granular bodies. In oneof the four instances the larger bodies appeared in a culture prepared from the brain of a rabbit previously inoculated with a culture of "passage" virus which had given rise to the symptoms ofrabies. In two of the instances the larger nucleated bodies arose incultures prepared from "fixed" virus in which Negri bodies weredifficult to demonstrate either in sections or in films.
The general morphological characters of the nucleated bodies areshown, magnified i,IOO times in the plate (figures 1 to 13). Alongwith them are also shown, ~ r comparison, Negri bodies taken fromt e bram of dogs succumbing to street virus (figures 14 to 2o).
The cultivated" nucleated bodies are actively multiplying, by divisionor budding, and exhibit the appearance not of bacteria but o f
protozoa. In size they range from about one micron to twelve
micra. Under the dark-field microscope, as in the stained preparations, they show definite characters. The center is nuclear and themembrane is distinct and highly refractive. The united individuals
in a multiplying mass may be enclosed for a time in a commoncapsule (?). By inoculating cultures containing the granular,
pleomorphic, or nucleated bodies, rabies has been reproduced indogs, rabbits, and guinea pigs, as shown by the typical symptoms
and positive animal inoculations; while the film preparations fromthe brain of the animals contained always the granular and sometimes the nucleated bodies in large numbers.
11 Noguchi, H., Jour. Exper. Med., 1912, xvi, 199.

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Cultivation of the Parasite of Rabies.

A f u l l e r r e p o r t oll t h i s s u b j e c t is r e s e r v e d f o r a l a t e r p u b l i c a t i o n .
EXPLANATIONO F P L A T E I9.

All microphotographs were taken from the fihn preparation stained withGiemsa solution. Magnification uniformly )< i,IOO.
Fins. I to I3. These represent the nucleated bodies of different stages ofdevelopment in a culture (second and fourth generations, five days old) preparedfrom the brain of a rabbit experimentally infected with " f i x e d " virus. In theoriginal material there were no such forms to be seen either in the films or insections.
FIas. I4 to 2o. These show Negri bodies found in the films prepared fromthe brain of dogs dying of natural infection with " street" virus. The bodies
possess central nuclear substances and distinct cell outlines (membranes). They
are usually distributed singly.

T H E JOURNAL OF EXPERIMENTAL MEDICINE VOL. XVlll.

PLATE 19.

(Noguchi: Cultivation of the Parasite of Rabies.)