野口英世著

Journal of Experimental Medicine

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MORPHOLOGICAL AND PATHOGENIC VARIATIONSIN T R E P O N E M A P A L L I D U M . *BY HIDEYO NOGUCHI, M.D.
(From the Laboratories of The Roeke/eller Institute /or Medical Researek,
New York.)
PLATE 29.

Now that Treponema pallidum can be cultivated artificially, it
becomes readily possible to consider the question of differences instrain among the species that may amount to racial variations.
Many observers have doubtless noted differences in the morphologyof the pallida in living and dead film preparations and possibly evenin stained tissue specimens. It would scarcely be possible to divide
the species into strains on the basis of such superficial characters;
but now that artificial cultivation has been accomplished, the question can be approached with adequate means for its solution.
During I 9 I o and I9I I, while carrying simultaneously ten different strains of the pallidum through the testicles of rabbits for many
generations, I was struck with the fact that certain strains appeared
thicker than others. Most of the pallidum strains in my collection
showed the thickness, length, and curves ordinarily recognized forthis organism (figure A ) . On the other hand, two of the tenstrains were distinctly thicker (about o.3 of a micron), and one was~thinner (about o.2 of a micron) than the average (about o.2 5 of amicron). The curves of the heavier type were quite typical (figure.
B), while those of the thinner strain were somewhat shallower and'set more closely, except the portions towards the extremities, whichwere again quite typical (figure C). These characteristics wereretained unmodified throughout the numerous transfers from one
rabbit to another within a period of over a year. Further, it wasnoted that the thinner strains possessed greater agility than theheavier ones.
As regards the production of testicular lesions in the rabbit, the* Received for publication, January I, I912.
201

202

Variations in Treponema Pallidum.

different types of the pallidum showed different effects. Seven
strains of typical morphology produced a diffuse induration andswelling, usually within three weeks, that progressed steadily forfive or six weeks, when spontaneous retrogression set in. The
thicker type, including two strains originally transmitted to rabbits
from cases of protracted chancres on the lip and prepuce, respectively, did not, as a rule, produce any change in the inoculated testicles until about five or six weeks after inoculation, when small,localized, hard nodules developed. Tile nodules continued toincrease in size slowly and remained sharply demarcated from thesurrounding soft tissue, attaining their maximum size in eight toten weeks. Unlike the effects caused by the typical strains, thenodules produced by the heavier ones were cartilaginous in consistence and contained a greater quantity of mucin. The thinner strain
that was transmitted originally from a mucous patch in a case of
malignant syphilis, always caused diffuse testicular swelling, within
ten to fourteen days, that progressed rapidly for five to six weeks.
Of these three forms of the pallidum, namely, thicker, average,
and thinner types, I have succeeded in cultivating from the testicleof the rabbit one specimen of the thinner, five of the average, but
none of the thicker variety. The pure cultures of both types were
found to produce typical syphilitic orchitis in the rabbit. 1
During I9I I, I have cultivated six strains of the pallidum directlyfrom human syphilitic lesions including chancres, condylomata, andskin papules. 2 I wish now to report briefly upon certain morphological differences that I have observed in different cultures of thepallidum obtained directly from human sources.
Of the six strains cultivated directly from human cases, threeexhibit the perfectly typical morphology, while one is thicker andtwo are thinner than the average. The average or typical strains
all came from chancres, the thicker one from a chancre, and thethinner strains were respectively from a condyloma and a chancre
in which they were associated with a regular strain.
Under cultural conditions, every pallidum strain is subject tosome degree of morphological change through which very long illaments, seldom seen in syphilitic tissues, with shallower or compara1 Noguchi, Jour. Exper. Med., 191I, xiv, 99.
Noguchi, ]our. Exper. Med., 1911, xv, 9o.

Hideyo Noguchi.

203

tively few curves, appear. But, when provided with optimum conditions, the morphology approaches the normal to such an extent
that no difference can be found between the cultivated and thenatural pallidum occurring in the tissues. When, however, comparison of the three main types of the pallidum is made under
optimum cultural conditions, the definite variations are easily observed. Even under less favorable cultural conditions, in whichsome irregular forms are apt to appear, the type characteristics
between the thinner and the two thicker forms can still be clearlymade out. Under distinctly unfavorable conditions, the differences
between the thicker and the regular types becomes less evident.
In spite of the morphological variations mentioned, all the strains
grow, under common conditions, with identical macroscopic appearances. Further, they are all pathogenic for certain species ofmonkeys.
In morphology, the thinner pallidum presents marked resemblance
to Treponema microdentium,8 especially when the microdentium
has been under cultivation for two or three weeks; but in macroscopical characters of growth, in respect to non-requirement offresh tissue for multiplication, and, especially in the occurrence inold cultures of a characteristic fetid odor, the microdentium issufficiently differentiated from this strain of the pallidum.
SUMMARY.

When many cultures of Treponema pallidum, whether obtained
from the testicular lesions produced in rabbits or directly fromhuman cases of syphilis, are compared, certain definite differences
in morphological character become apparent. The different specimens can be divided into thicker and thinner forms or types, and anaverage or normal form or type. The last is the common or mostfrequent variety, but' the other two occur with sufficient frequency
and retain their characters with such constancy as to constitutedistinct varieties. Indeed, two of the varieties--the average and thethinner--occurred in association in a chancre and were separated
afterwards in cultures. The gross cultural properties of the threevarieties present no points of distinction.
~ Noguehi, Your. Exper. Med., 1911, xv, 81.

204

Variations in Treponema Pallidum.

T h e lesions caused in the testicle of the rabbit differ according to
the variety inoculated, and consist either o f a diffuse or o f a nodularorchitis. This is a highly important distinction, and if, in the studyo f a still larger n u m b e r o f specimens o f pallida, it is maintained, it
is capable of t h r o w i n g light on certain important clinical featureso f the h u m a n syphilitic disease.
T h e thinner variety o f Treponemct pallidum resembles in m o r p h o l o g y Treponema microdentium, f r o m which it is unmistakably
distinguished by cultural characters.
T h e morphological and pathogenic variations in cultures o f thepallidum m a y constitute racial differences within the species.
EXPLANATION OF PLATE 29.
FIG. A. Regular type of Treponema pallidum. Schematic reproduction.
FIG. B. Heavier type of Treponema pallidum. Schem.ati¢ reproduction.
FIG. C. Thinner type of Treponema pallidum. Schematic reproduction.
FIo. D. Various forms of the thinn,er pallidum in a pure culture. Schematicreproduction.
FIGS. I ant( 2. A long form~of the regular type of the pallidum. From a pureculture thirty-two days old. X 1,4oo.
FIG. 3. Average forms of the regular type in, a pure culture two weeks old
X 1,4oo.

FIG. 4. Agglomeration of the pallidum of the regular type. From a pur.~culture four weeks old. X 1,4oo.
FIG. 5. A paIlit(um of the thinner type. From a pure culture three weeks
old. .X 1,4oo.
FIG. 6. A pallid~m of the thinner type. From a pure culture three weeks
old. X 1,4oo.
FIG. 7. A pallit(um of the thinner type showing deeper curves near one end.
X 1,400.
FIG. 8. A group of pallida from a pure culiure of the thinner type. X 1,4oo.
FIGS. 9 and IO. Masses of en.tangled' pallida from two different pure culturesof the thin.her type. )< 1,4oo.

T H E JOURNAL OF EXPERIMENTAL MEDICINE VOL. XV.

PLATE 29.