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Infection, Immunity 


Serum Therapy 

In Kelfttion cc the Infectious Diseases 
of Man 




lUfbM lOd Initrgri by The Author and by <ifD- F. Uicli, M^O., 

loMiuVr in Pjfhul^tip, IJnitmttv urChicip, *itti 

Pr6v by Ludtii HtlEf«q« M,U 




By thk AUKKirjiN MUhc-ai, A»)|i»ciatiun~ 


The circumBtancea that ]ed to the first publica- 
tion of this book as well as its general scope and 
character are explained fully by Dr. Eicketts in 
the preface to Uie first edition. The book met 
with ench favorable reception that the edition was 
exhausted while the demand continued active. 
This indicated that an actual want had been met 
and 50 it was determined to publish a new edition^ 
revised and enlarged, and for some time previous 
to hiB greatly lamented aud untimely death Br- 
Ricketts gave freely of his already heavily taxed 
energies and strength to the work of reviaion. 

Sorely a simple word or two in tribute to the 
memory and achievements of Dr. Bicketts are not 
out of place at thia point. He died in Mexico City, 
May 3, 1910, at the age of 39, from typhus fever 
which he was inveatigatiog with splendid success 
when be was taken ill. Thus a noble and inspiring 
career of large service to hamanity and of rich 
promise came to a sudden and heroic end. During 
his short but intensely active life as an investi- 
gator in the field of infectious diseases Dr. Rick- 
etts made important contributions of permanent 
value to medical science: he greatly advanced our 
knowledge of blastomycosis; he solved the most 
important problems in the cause and transmission 
of Rocky Mountain spotted fever, and discovered 
that this disease is conveyed by a tick (Derma- 
can^ vtmatuB and D. modestus), in which the 




InfectLOJi 11 lierediinr^', thereby enlarging our 

iiador«tnncling of tho part mfccis in£T take ab 
earners of ilii^teas^; hn ■TiMnonstrHtnl tliHE the 
typhus fcrer of thr Mexican plAtcnt^, tabardillo, it 
airriud by the hody bus? (Pudirulvji v9ttinifnii)^ 
•n(3 the results nf ]m W"irk on tliiB inpense. which 
he had only just l>epuu. will hr of fuiidamentn! 
wgnifiiRnto in ib prevenlif^r and in nil fnttirt 
inveatigation oB to iU calis? ond nnturc. In hit 
d«ath ''oD the firmg line" w& lost an invo^ti^ator 
of Oit" fii'st rank wIkiri^ name Uirough th^si- ncliirrt^ 
mcnf-"< will live iri the hiflti^ry of iripdicfll yicnrc, 

WUph the pap^*!!" atid mamicrriptp left by Pr. 
lEiokettj^ cantQ to he examined it was fouuil tliat 
vhrle the work of revision and enlarf^cmont of thia 
tioiik wn* xtry fur fnim cnniplete y*»l he Imd car- 
ried it so for tliat it ft<?frnicd nnviee rot in nttmipt 
to Cftny it throiigh ro completion- Fortiinaiply 
Dr, flporup F. Dirk wat willing to take up tht 
unfininhrd tniik- which proi'crl to be ft TOUch Iflr^r 
mie than wnn mitioipatpi? T^r fht' reiisofi thnt, in 
addition to completitif; the revision and adding a 
Gon»i<lcrab1c amount of now tnat^riaE, it was n&?ea- 
*nry nl«> (c ■PCiirc prO|)pr rnonlimition and hnhinie 
hctwt'cu th<? diUcTont parte of the boot. 

The hook U now diviiled into an inlrodnctioii 
luid Ihrre part* in^tcatl of two as in thf first edi- 
tion. The Introduction and Part T wcro prcpnrcil 
by Dr. Tticki^tt8 and the ohaplers on "Sources of 
Fathofi^eme Micro-orpanitjtifl" and on '*8pooial 
Ft'utures of lufoPtion" fir* new. Part 11 contains 
new choplere on '' Com pU mrnt- Devi utii^n," "Op^o- 
nins/* and "Anaphylanip " and Part TIT ^hapt*w 
on "Epldi^mio Poliomyelitis." "Noma.*' and "FTala- 
Aitr." all by Tlr. Piek Tlic old chapters in Parle 


II and III have been revised by Dr. Dick in the 
light of recent work and eome of them largely or 
wholly rewritten, notably those on "Syphilis" and 
"Spotted Fever." Aa a result the size of the book 
has been increased nearly 300 pages. It has been 
the aim throughout to follow the lines laid down 
by Dr. Ricketts in order to secure an adequate 
presentation, suitable for physicians in general, 
of the large eubjects of infection and immonity 
as illnstrated by the human infectious diseases in 
the light of modem knowledge. The present 
intense and widely spread activity of investigation 
in these fields, with its many discoveries, is giving 
ns new principlee and methods of treatment, cura- 
tive as well as preventive, and of diagnosis, which 
require a thorough mastery by the physician in 
order that they may he used to the best advantage. 
It is my belief that this book by Dr. Ricketts as 
revised and enlarged by himself and Dr. Diek will 
he of real service to the physician who desires a 
reliable guide to a helpful understanding of the 
subjects with which it deals. May the use to 
which it is put show that the labor expended on 
it shall not have been in vain. 

Lddvig Hbktobn, 
Chicago, May 5, 1911. 


Immunity, in its present state of development, 
with its manifold new terms and special methods 
of experimentation, is a subject which appears 
difficult to one who has not studied the newer 
literature assiduously and grown into a knowledge 
of the conditions through actual work in the lab- 
oratory. Much of the literature is technical in 
character and appears in journals not commonly 
found in the hands of the physician and students 
Much of it also is comparatively recent, and its 
"essence" has not yet appeared in books which are 
in general use. The literature of immunity, more- 
over, grows so amazingly that the analysis even of 
current works is a task of no mean proportions. 

At the same time, the subject is one of great 
interest and importance, and there existf a gen- 
eral wish, frequently espressed, to know more 
about the recent advances and the conditions which 
have operated against the success of n^rum therapy 
on a broader scale. 

The editor of The Journal of the American 
Medicai Association, appreciating the need which 
seemed to exist, requested me to prepare a series 
of articles on the subject of ^'Immunity " which 
shouJd present the general principles and th? 
important theories and facts, in as simple a man- 
ner as poflfiible. These articles appeared from week 
to week daring 1905 in The Journal of the Amer- 
ican Medical Association, and after revision, and 



whh ffiicli nd<iitioD» a« would contribute to lh« 
completeness ol t^io work, thoj are now colJeclod. 
Ill luT'^'i (\\\v, in \.\^v pre>^nt vu]tr[ii« uiii] uridtfr « 
more suitable tttle. 

It was thoof hi beet to treat tJic subject broadly, 
Ui begin wilh ibe f inula mini till prinHplw nf infin*- 
tion tin*\ reabtnncc nrjd to Tctroducc the reader to 
tbe more eoropl^Ti roneeptioTB of the preeent time 
by tsking him briefly oT«r the main liibtorical and 
df'Tclopmontal ftcpst. 

It will be obvioni thot Uio vltvt ot EbrliPh» 
(oncf^rninc thp production nf ntilibodie*. the nfltnrc 
<tf tho reaL^tion^ into nbieb tho lattor enter, and the 
methods by whieh haeterift jirmhire ilf-<4*flr<4'. bflv^ 
been ntiliEcd fxt*nwivrly. This rour?c demnrnl!' no 
JuHiilcatioR, when il is apprecintod that by no 
other meern can oni^ nt the present lime corrt-bile 
n nmltitmlr of weIbe»l«bUBlied faetf wbidi betr 
on tho problems o! immiinitT. Wbaterfir may be 
Ibe eventnol fnle of Ibe sidt^-bain tbeory — »fid 
terUixj pb^ten uf U carry Ibe aspect of ficolity — we 
flbould ApprcciAtc na much m possible tLie extent to 
wbieh it httft Rhaped mrdern thought, and reco^ize 
Ihni it hM wiin Jin I iiL|>er]3!iaMe plure In Hie hii^i' 
lorv of biologic pro^eas. 

ft abouM atfio be nndorstood that ibe titifization 
of (he vide-HiniD UuMry in no spnse carries with it 
a QCgstian of the importance of pbagocytttsie, a 
fad which in plainly ?et forth on pagpa 3o$-7p 
Wit)mut flouhf the rfllc of the phagocytes in reeoF- 
ery from a large group of iofeetiona ia od a l>ettpr 
and truer bflvin thnn it Iidh ever been before, and 
for tlili condition the reec-nt work on opeonint hai 
been nio»t fli^niflcant. 


In relation to the grouping of the infeetiona 
diseases adopted in Fart III, attention is called 
to the eiphnatory paragraph, page 398. 

It will be noted that a bibliography of the sub- 
ject of iramunity has not been added, and this 
needs no explanation to one who is conscious of 
the maeBive proportioDs of the literature. A crit- 
ical analysis of the entire literature, which would 
not have been in harmony with the endeavor to 
present the topics briefly and clearly, and which 
would have made detailed references esscntialj has 
not been attempted. The most recent literature 
on the various flubjeets is aeceasible through the 
Index Medif^us, or the Index prepared seini- 
annnally by The Journal of the American Medical 

The index at the close of this volume serves as 
a glossary of terms, the explanations of which roay 
be found on the pages referred to. 


Chicago, February, 1906. 


IntroduFtion : Hietorkal and Derelopmeatal 
D«U 1-12 


Chaptoi I. 
PBnftitism, IflfectiousneaB, ContagiouHaeH§ 13-21 

Chapteh IL 
InfHtious Etiology 22- 32 

Chapter III, 
Inf«ction Atri& and the Excretion of Micro- 
orgaaiftmi 33' 40 

Chapter TV. 

Sourrea of Patfaogenic Micro -OrgaaiamBi 

1. Earth, Etc 41-42 

2. Food Subatanccfl 42-43 

3. AntDMlH 43^ 45 

4. Body Surfaces of tb« Individual 45-46 

OlAPtEl V- 

Sourees of Pathogenic Micro- OrganiHinB {con- 
tiaued) : 

5. From Man to Man 47-63 

chapteb vr. 

SourcM of Pathogenic Micro- Organ [sma (con- 

A. DiBBcminatian and TranamEssion hy 
Insects : 

A. Dtsaemt nation , , , . . . 64- 67 

^ B. Transmission 67- 87 


con 7 SffT». 

1 V:rulpni?i?, Tcxieitj, Klo- - 

fi. 'r^pTE bf Inf Milan,. ,., , .,,. 

t. Naturt fiod MccIuuUm of laftcUon. 

. S8- M 



< iiArr™ VIII. 

Typta of Immunity- ,. ., .. , iSS-lSfl 

nrApm TX- 

Xulunil Immunity IST 

I. Prr>lwir<m Afford^fl by thr Vindy Surfne'^h I37>J43 

A. liirlpinEtiiition U3-H1> 

B. FropcrticB of Uic SeJ-Utn And Plaanifi UP 1 Oft 

AcquirtU liiimilnlly. . . , . .. lti]|T5 


Totin* and Antilr><iinB. . lid IW> 

OM.u-rth XII- 
Hw ''Struoturv" nl Toxins imd Antltoniim pud 
ihf N«lurf ckf t}ic ToAifi-Aiiti -Toxin llotdloti. ,lll) £05 

C'»^1>TKk XIII. 

Tha P1ifTiain«non oi X^Ui\\JiM\an . ...SOfl'SIA 

CiiArrKX XTV. 
Ilic Naturr «f the Sub^taiicn Concrr&cd in 
AAtflutjnation , , -filD'Saa 

Pipclpltlnd .., -.. .ia4'24« 

CiiAf-rn XVL 
A' Ofnor*] Prop«rtici of llacltni-idKL S*nui». , .SiG-^SA 
B. mmoh-iiu SU-3TS 

Chaptix XVI r. 

Complemeat Deviatioa 27B-201 

Chafteb XTIII. 
CytotOEim 29£-30fi 

Chapter XIX. 

PbagocytOHiB 306-323 

Chapteb XX. 
OpBonlns 324-336 

CHAPtEft xxr. 

The Side-Chain Tlieory of Ehrlich and Its ReU- 

tion to th« ThMiy of Phagocytosis 339-361 

Chapter XXTL 
Frincipli^s of Serotherapy 362-380 

CbapteB XXIII. 
AnaphjlHxU 331-307 



Gaour L — DiHi:ASEfl, Natibal ob Experiuextal. 
Caused bt Soluble Toxj\»i of Bactebiat., Amual 
oa PLA^T Obioin: 

A .-'^Bacterial DiiCQAfs; 

Diphlherifl 39S-408 

TeUmia 408-419 

Botuliam 419-422 

BacLllufl PyoflynneuH .,...- .422-425 

Other Soluble Bacterial Toxins 426 

B. — Intoxication bj/ Soluble Plant Toxins' 

Raj FcTfiT 425-427 

Other Plant Toxins 427-42fl 

C- — Intoxication by Soluble Animal Toxins: 

Poiwning by Saake Bites 429-431 

Other Zootoxins 431-432 

OtiCVF 11. 
A-^Tht Smtnt in Afqittivtl Immunity U Imfttatttd 

Typlioiil Frvci. .,., 433-440 

I'flT* lyphold FBVfr 440-4a3 

Aout* KplilcDkld Dytenlary flG3 45W 

Mut Pol»Ttfne by DacIIIuft EntcritldU 4^1)463 

ndclllufl CoU , , , 403-400 

I hnlt^rn ..... ... 4U11-4KU 

Phxii\»v -ISl-JM 

a.—DiiKaiiri in Whttih At^iuircd fmrnunfiy in ;VdI Due 
tfi /nrrftijHvJ iSarl^iri^al Pr>irttr w/ »*<» S(ii»Ti»", or 

AiitltfUK ..iwp 492-41)8 

MftlU F*vw .-, ,-,4flfl'ftOO 


Qwovp III. — AcuTt l^rEc-^lo?ln is Wpicu L*»Tr5<i 

lltril'NTTT m "Sov K«r*HLT«im. 
l*npuuiowwuB Infections — rncumoaift. ..,,,.,. .liOl'&lS 
StrfptoccKTi . ,i . . . i ..,. .fil5-337 

Suphylorowi fi37.5fln 

HtcriMOcrii* Latjirrbciliq , ... , . . . ,C£0-5GI 

Qdnorrhon and Ollipr ]nf«tiOEU wtth tht Oono- 

GOCCilH .551-550 

KplJi>iTii(i OfDlirMpiiiul MfitLin^Jlifl ^rti;.*^;! 

Influonfn '...-.,,,, fiH3-5rtt) 

Soft L'hanore GOO 571 

Rtirillii)! cf Frlfillnnrif^r Bod Other Uemben of 
Llir Cii|iftitrr-Fviiiiiiijj Oroupn-, > , ,^ 071-&T2 


GlOiT TV. — riiBOMr IsrccTio^fi iiv Wiiirit L*wnvj 

IVUL'MTT tii Not Kstapi mum. 

TuU-n-u1u«i» 5M-015 

T^ro4y Atti-ii^:! 

UlftDdor* ,. . . 033-ll2n 

Khiiioidrniin* 020 

ActUomjoiMl* nSA'dSn 


Madum Foot B33-B34 

Infectiona bj Streptothrix* Cladothrix and 
Leptothrix 634-835 

Oidiomycoeia 636-641 

Chapteb XXVIII. 
Gbouf V. — Diseases Dve to Sfibilla. 

Rdapaing Fever 64a-fl4a 

Byphillia 640-662 

Fr-HmbeHia 662 

Other Spirochetes flS3 


Oboup VI. — Pbotozoon Infecteons, 

Malaria fl64-670 

TrypanoioiniaBiH 670-084 

TeKas FflTer 084-086 

Amebic Dysentery 686-000 

Sarcosporidia 000-601 

BaUDtidium Coli 001-002 

Cercomoaaa Inteatinalh 002-003 

Trichomonaa 003-004 

Coccidioflin 004-60S 

Kala-Azar 006 


Oboup VII. — Dtseahes hf Doubtful ob Unknown 

Hydrophobia 607-710 

Yellow Fever 711 720 

"Spotted Fever" of the Rocky Mountain Staten . . 720 726 

Typhus Fever ' 726-728 

Dengue Fever 728-72D 

Acute Articular Rheumatism 720 

Smallpox and Vaccinia 720-743 

Chickenpox (Varicella} 743-744 

Scarlet Fever 744-747 

Meafllea 747-750 

German Measles (Riitheln) 750 

Whooping Cough , , , 750-766 

MumpB 755-756 

Epidemic Polioroyclitia 766-768 

Noma 768 760 


iiiM'nmiuAL AM) rjKVKi.ui'MicxrtE, 

'Vht concepUon of thf^ miturc of immunitv icnrtr Timn 
whieh wft* current at one period or anotlier of ^^^'*'*" 
Tiistorj liftil wme rcUtioriMiiip to U:*; cnnccptinii 
of the etiology of iliMftMa at those timcA. tt will 
be renienib^red ttat at cue time iiaOA«<c« woro 
inip[Mue(l tu \tv Lm{K>HHl by nn niigrj d^jij, aiid to 
avert Ihcm vntious lay.'ticiem* vrcrc resorted to, 
iuch a< the utterance of incaQtalions and the 
wearing ^t tJilifimjmA- On tlit nUmr linnet, n mnre 
logical Attvinpt to <jJ!p1am the naUira] immunit^r 
of ifae PsjUi against snel^e poison ^vac marj? b^ 
Plin/, ulia suggD«tc(l llmt it night ht? due to Uicir 
habit of drinkiog water frc»m weD* in vliioh poia- 
onouft Ennkis rln-i^U, TltU j« not unlike our ptva* 
ent oo<i(H!p1iofi of ul-Iiyk imtiiuiii^uliou. 

Von ISchrJog quotes litoratjro to ehow that 
anieikg aome pHmitiiM^ mcec of to-duy, urtiEldal 
immiitii/ation \» c-itrriotl on; ti Mo^amliiViue tribe 
lA Mid to inoculate offajnet Anakc poi»on by rub- 
bing into a small cutanwna ineiaion a paetc which 
contnmi vftiom. Fmbnlily non^fittnT qnnirtitiM 
are introdijccd in ttiw "'av. refultin^ in Ihft fomu- 
tir>n f^i vi'tiom iintitoxiti^ o method comparable to 
that U9cd In the prodnctlon of diphtheria anti- 

At ft Tory early period the poaaibility of habitua- 
tion to poiwnoufl ilrug* wm rttro;tm3y-sl. Wp Iriirn 
that Mjthndattt by taking jn'ix^i^nlly i&creaain^ 
doeca of poienne ectablinhod it himeeir r«eutan(^ 


;.vfi;c//o.v A\D tJi2iu:^JTy, 

of thia tort. It fa BtAl^d alio thai ha fed dudef 
ttttli poiHOiiB and thea propcmxl io uiw tlirir blood 
ft* an uiiticlcitii (flpnim UiPvapy). VU^ iinponanoc 
of niitidotea ir the minds of tbp ancients may i>ft 
apprcdatcJ from Ihu fact that epiJemic disease*, 
suoh as plagiie, oholero and tmuUpox, vere at one 
timi; OQUbiderei] as iliie to uiiknnwii polgoQii, which 
might be corapnrable in nalurc to pome known 
poisnna, a^ aconite- Mk-Ttinrv for svpbiiif, f]iiinm 
for mzUari^. and ^alic^'lJc acid for rheumatism 
would pcrtainly have fallen into the calcp^ry of 
antidotes, £ii(] inei'(fi:rv niJiy hnve het^n va tioti' 

A historic tlluetratron of the treatnieDt of dia- 
vuei- mi A Bupp^JHtJ etiohigjt' bnaJR in found iti ii 
lli«ory which ^Tie prevalent in the eovcnloenth 
ctnhiry, RCCDHiiig; to ^ihich dtwiises iv(*rc- i^iihrr 
acid or ba«ic in character, and licnce nhoiild he 
treat^p th9 ODo iviUi an altali. ihe other with an 
acid. SjKiuft considcre*! plaguo t/i Uc of arid 
natnro and ndminietercd alknlie^n while hiliniiller 
iooV the opposite view. 

Mauifi?st!_v^ rational trtuitiu'iii and pvopliyla<i» 
of the inf<"C^ions diseasre could not bo undorttikcn 
until tlielr etiology was correctly understood. Yet 
hero, OR 50 often liappen^ m medicine, empiricisoi 
precede-1 ration a li&m. For example, protpetivo 
inocifliition did not Ijocomt? a prinoipic nntil the 
tirao of ?Astenr, yet it hud been practiced against 
»ni&llpox for centuries, ajid the method put cd 
it* prr»^nt h«>tiK hy Jeruier long before tliere was 
Any idea a* to the principles involved in the pro 

The belief that invisible "inimalculea" are able 
to contc morbid proocesoa in mxn U a vary old 

TNK tf/CJfOflCW/'tf, 

A pMsage from Varro <Ua-37 B. C.) rc&di 
AS follott't: "Th*ro *r* ift-acip}' p]ac« in which 
grov animsb ncTrr no »mn)l vtiidi maj nai he 
ncogti'ujcd by the c^, unj uhidt s^^n a<^L«K4 to iht 
bo^y throu|-li ihQ air nttd bnng £boiit i«t«t« 

'Ilio discD^^rj and lum of the compouaJ nucri>' 
•oope in th« eotcntponth contnry dt&clo«dd t)i« 
rooJhj of tha minuto living formi: wiiLcb had been 
Mtiiipctcil HO nfteu. KirE^lier, with bis fint crade 
miCTMCopc (I(HO). cianuiied tlie tiMuoa of Ta- 
rioud dieeoMM. and mos tho niithor of many th#* 
orles M 1o thrir ettolo^. It i* now bcli«AYi(l IKat 
the mngnification of Kirchern micniftcopf; va^ fto 
email that many of the "worms" which he saw 
w*ro rMll}- IflTgd fongOHfi *^1Ib antl in -iome in- 
rtjncvs thn u vn iitiidnitifitMl IiIwhI an\\ piu c^elli., 

LMniwrnh(wk (ltJflM733), a I>ntch natiiralK 
with hi* compound microscope nugnifying 1,000 
diometen, obfttrved flcc'unib!ly nianj nuGrob^jufuc 
fbraw, but madp nn jipplicjttioTi of his Hisco^-erie* 
to modicnl problems; a«vcrthc!ciis, such applica- 
tion waa not wontiiifr. &nd tho enccooding cODtury 
ftDd n half Htw fiich voltimitions deii^rjptioiu of 
miRroboL, tM> iitjuijr couUuUiclcjt'y U:wriGa and 
•tatonenttf ccnoeniiiig their r&J&tioiiship to in- 
feotioiiA, t!]ut tho "in^nttoumally amaJr^ fell into 
diufnTor in itmiiv c^udrL-r^ hK Vw i.*n\i*at ttf di*«uarkM, 
The attractions and rcAMnablancfs of the theory, 
bovcvcr, were inch that it conttnucil to fam ox- 
poiiCEtt^, and in the ear}y part of the ninccconth 
foitury reachod a degree of doHniteDcu. In lSr»j. 
the jjTtat French pbyaidan. Britonneau, a^rmcd 
thai a tp«eilk fprrm vra« 1h# eaxifi^ of every con* 


tSFECTloy AND /JfJftT.V/n". 


UgiouA disease: ''An opi^emic dieesse can orig- 
inate and ^jctead ouly thiougb tiie agency of Uie 
gorm prodin-'mg it." Yot at thie tirae no infee- 
tion Eind l>cvu JKiitiilely proved to be of mitrobic 

Jn Ld50 Rfty^r anJ l^ovama made aa cLacrva- 
tioD, wbici) might liave fallea into (l;e obllviou of 
many procoding onea had it tiot been confirmed by 
later invesJtgatorfl. Tlity found ''small filifiirm 
bodiea'' in tlie blood of theop which had died of 
ftnthrai, and were naturally iocUned tn beliove 
tliflL UiRsi' foniis rntififd the di>ea*e. Otlier wieai- 
tifife, tspocially Ca^tenr unci Kwh, eoon took up 
the »4tudy of anLhrjix. with the roMuU Unit Iho 
soiall rod* of Devain^ were scientifically proved in 
be ita cause. 

7Vo great minds dominntfl racdicnl reaearch 
at thJe lino— PAetflur and Koch- Pjatcur. in hie 
eai'ly oareer aa si cberiiiHt, Ijnd had his atteiUioii 
colled U> the prooeasT^s of fermentation. He re- 
cnrrod to tht^ subject at r tim^ whitn the theory 
of the spoataneons geneiation of ainall living 
forms waa viiddy diaciiBacd, and m 1S5T-I861 
proved beyrjnd iiny jyjMihility flf doubt that laetic 
acid, alroholJc ornJ hulvnc acid feniieritations nre 
duo to tbe aetion of minat^ living eellfl ^ and. fur- 
thermore, that each particular liind of fei^menta- 
tion baa its own peoidtar mii^pobe as the eau&e. 
Thifl vFfls an example of what we ierm to-day mi- 
cTobic fcpecificity, in mnrKed controet to viewa 
which were then prevalent regarding tlic variabU- 
iiy nf miero-i>rgjini«m(&* Pasteur thfiii applirti 

Ibll Iden 01 UDltmllrd vnfUbllttT of mlrrnbu* : 'U thr 
fOrm* flf tfpriorntlrtn« thr- *im" <rTrtptf*v aniiiU'** o^trirnT 
1lUl> Illflr?r^i]t iiiorL>lit>1r|iknl iind LktirvLDlOKLfBl fvrui« vrlilfb, 


whit lie huid \ttTi\cd about fnrnifrntationA to the 

atndy of ttw diH«£of *>t winofl tud boor«. Ha fcnnd 

iheir caufiCfl. And dt^^i^ed a prev^Dtive m^a^nrc, 

which cooftiatetl wcrelj iti th« de^irunion of the 

gimtf b>- healing tli« hido to o fuiUbI« t«u|Mr«* 

(qi« Wore it v« ^rcd- At tlw iD&tanoc of tbc 

French lEOTcmiuent, bo then studjed certain dU- 

tmm 0/ HilkvromibL Hlfl suA'aa in discovering 

thdr«ttUi«e and prcrctiUou mxtA &lw&re noiaiu for 

tu one of the laudinark* cf the TOrLri progr«ft. 

It wv during tbc Uitvr iav^c»iig:alion£ xitAt be 

CooJc up (he etudv of atithrox. The qMcific mi* 

4?robe harlji^ been dl^covere^, uud the rnethcKls of 

tmmniMioii of tbc malndT huviuf; bc^m itiado 

cUfar tbrocigli invoAtigntiorm by boUi Piutour tnd 

Koch, Paateur tun»d his attention to mctbcHie 

of prei^ention and^ it poesibJe, of enM. 

Paalfittr j^ndcrod the qu«tion of iinaltpox Tie- r»*^tmm- 

ciDOt]i>ii. Jlc came to believe that vaccinia i§ 

nnallpOT, the Tima of vhich haa been ati->Tiiiated 

hj ita pa^aage Oirough Uie ixmr, and that con^«- 

qaentlj vlicn man uitdcrjtoea Taccinotioa be then* 

by U inocaUtn! with a bfinign fi>nn of the rfi^^etAes 

3licbt not thid be an exajuple of a law which would 

be (fen«TBl tn ita application? Tbe protactive inoe- 

ulalioo (adivt- immuniMtlinn) a^inut thp plrtiro* 

pneurooniA of cattle which had bog been prac* 

tinvl ^V9 ann>nnigmi^t to thta hopa Somi* 

work hy Touaaaint vtt^ important in the answer 

to thiii qnofttion. It vhm errdcot thnt a wnakcning 

or attimnatinn of thn hnrt^na op inrun miint flntt 

•vonof Dt mUB. mcfv QIC fDrm'ilaii ct bqirrtf mr-in in uiii*^ 
kr>*l. Di>« fti« fovn^miMom of alnt. aotr iht dccampoBLllOB 
9€ fttbaDluovt tDtiirr>. now Ibo nllttlaf np at una, now 
ibfl r#tf rotar of vtiirTbr fia4. anil gfre r(K aov (o tllpbthcrla^ 
Q0ir 10 iTptrnlil f«Tvr amr ta tvrctrrrni trtrt. roir lA 
cboltrfL mow in mnEulAl fiTrr.'" lC1lf4 froia i1<ata«lla I9 
Oalct^ ixvifDi nr iiQii'TD u#ai£iDtf; t«i. i.i 

till Ik- 


b« obiNlneil burtire it vonl<] Uv wifHy mj«-'tai] into 
&nimal« for the purpo«c of proihicing immunity, 
for if th« unaltered virug wero inje(?ted the viru- 

AailirniH U-ul iiifeuUon wouUI resuU. At'corduiglj, Toiia- 
flwint hpiited the blood of a slicep which Jmd ihod 
of antlirflx, to a Umpernture of .'ift^ C, for U:n 
minute*, tlien injedetl it into a number of alieepp 
Somfl of the unimalfi dietl of antlirax, while otberi 
»uiT<Tf»<l onlj' !L mild ntiact horn which thry rw- 
covered: tlie latter wtro found to bo ioimuno to 
B iub«qiient iDOCuIatiou with virulent blooJ. [n- 
aj^mncli, Iiowevcr, us -*nmc r>f Timwuiinta animals 
had died of anthrax, Pftfttour connhidoi that there 
vnHH some grave error in tEcliiite, He considered 
that Touwaint's melbotl probably killed or atten- 
uated t^ic fully ^[]ovelo|ied baoUli, but did not in- 
jure the spofc* of the parflaitc (Koeh hud pre- 
riouslv aliowii the exiatoflco of anthra:c ?ipona). 
Afler much et[n?rimeii[Ati<]ri, Piiiitf*Lir hit oti the 
plnn of growing the bfldlluj nt a tcmporaturo of 
42' C, obtaining in thig way a culture of tho 
fully deieloped or^anij^m whicih !»ad n Inw viru- 
lenee, but which did not form thr daD^rom* 
fporcK- When sheep w^re inociilfltpd with the 
proper amount of ihig culture, wliicb bet-ume 
Imown Qs Anthrax \JLccino. they had a mild attack 
of Un' diaenae, whicJi muh-n-d thnm immunn \a 
virulent inoculfitiong. 

Wttli the possibility of protoetivo luoculatioa 
with a known \in3g actually demonstrated, sim- 
ilar procednres were tried with other animal dla- 
eag05 of known bacterial etiology, with the rogult 
that Aucce*sfid vwtrines ft^^JiiiMt i-hitikim cholera 
and &wine plague were devclo|>cd. Somevrhat 
later, hnving fnited in their attempts to diacovor 


THKtitriKti fiF iHjavxtTY. 

tbc mfcTobea of plague and eholem, Paaicur and 
hisK L-o-vi>rkcr» tjmed l<i ttic *turJy of liydroplio- 
bifl. All cfTortd to cultivato tho vinif? from tli« 
fljhinnl i?\M\} of rabid dogs ffliled, nUhoiigb iroeids- 
tioQ exin^riiiieiib proved iLs prcK-tjcc in tliia stniC' 
tiiK', Tho imi'iuc idrji Uiea oorurred to con«idoT 
tin* inf<^ti*d ftpiitii] nm] i\r. n fully drvebpod ciiU 
ttrrc of the vinis. It ronijiinod to itvbjcci such a 
eulliirc lo tl»<; praper aU^iioaling conditions fur 
the puq>o4e of wcflkemns or actually distroying its 
viniltaicv lit order to make it fit itir proleetive in- 
jections. Tliip n&f ai'i'ompl isf j<.n] hy drying tJie 
cQTda in & closed vo^d over ft Ji^^^ecopic sub 
$Uax* (K»lid pctaatfum livdtojid), tlii^ fiiiHl vim- 
IcQC* oC tlic cord dcpcitdtng on the length of hnie 
it had b««o fnbjcctad lo lli« drying proce^i- Tlie 
teL'lLHic of the protective injectioiia, Ubt- auci;*^ of 
whtt'h ie hciTF^vholil LDovtr[(<dp>, witJ be ft subject for 
ln(i*r ooiH]di']"aU<>H. 

Of primary importance, dnring this period, vnr i^vn 
iht work of Koch on the apocifio bacteria of tn- rrt^nViplSl. 
h4trctilnHiit, diolprn, typhoid and Uh' pyop-nii? dli- 
eaw*; and not Icait hi* impro\-cd method* of ob- 
IfiiDiDg pure collurea tliroiigb the uao of tolid 
m«iis (gFlstin) on pUtr«, Through h'm work oml 
that of Paakur Iwo groat priDCiploa had loen 
Mt in motion ; tho miorobitr flpodfic*ity of infocticut 
ditf^iJiM. and priiW'Ur«> iriiKrtilalruit in iitt j(i-iierid> 
iKCd form, through tho use of attcmiated rirus. 

The fcicntific mind lunic<1 at ooco to tho In- Tb«*^i*«> *t 
f\\>''Ty, What Hi:ing;pfl in nn nnimnl br»dy tirtt rw- dt*i«fn'nniiT- 
ipoanihte for iht. immunity whirh is acquired w 
th« result of protoetiv^ inocnlaiionp ? Also, tapoD 
whil pToportifti of thn 1iniiP« or body fluitU do*** 
tbo nntnmj inarQnnity at au animal dopend. and 

rxyjcvTios isn /wJirv/rr. 

Tfe^oFT. ^^jQ aliK-ntr of thfif^e iirojwrtieA which characteriM 
the nntumJ imiriunhy of OQothcr vpccies? Vta^ 
teur had obaan'cil that if be ^ew tlic microbe of 
fhirki'Ti rlifilrrn in n HfjiiiH mcdiiJiTi fnr unmp timp, 
then removed fhc bflctoHn hy fihralioti, the fluid 
bocaiDQ xm^i for the further growth ot the organ- 
iirm on nuh'tf^quopt rojmjpiilnlion, Thnt i», the 
milrient matenul \\n*i h(:&i\ uaeii ujj; luu] hta »Mg- 
ecc»tcd that tliiG in Chu <:Aae in the body of on &ai< 
rnal. Having nudorgone Uio infection, suitable 
nutrieoL rnat«rijil for ihd miciohc is usGt] up^ and 
recovery eneuee. Tlie prolougod abi^CDce of tho 
proper Qutritious BulfltaDcea would account f>r 
tho more or Ir;<s p«miunent uatiire of thn notjciirRd 
immuuitj. This conception, the exlmiaatioTi 
theory, at one time ahnred by Koch and Klebs, is 
«ill rrproKenTfld in nn w\i*^rci\ fonn by Brtumgnr- 
tuji, who speaUe of an unffivorablc culture medium 
AS rcprwcnttng the condition of the iinmuna bfjdy, 
whith^ of com"s&, is broadly Irue. 

^»ijuu> (IliLiuvtiJiu (*itsi thu HtiUiur nf iirifitlu^ hislcinc 
VTiViiry, theory of ficquii-ed Inmiuniiy (the ftr>xiouB reten- 
tion theory) » which maiotmnod that during the 
i?oanr> of n diNL![t<tu Uie bjU-'teriu produo^ jtubslaTici^ 
in tlic prcscnci- of which ihcy con not develop 
fiirthrjr; conscqiicritly recovery tiikca phice, ocd 
the continued proflenco of theie noxioni eubatanee^ 
r^Hrlei!* flnother attack of the disease impowsihtu. 
Although it is tiuc t^ot bacteria do not ^row well 
in their own metabolic prcduotAf theories of im- 
munity on Ihf* and similar bjwra an? not in nit- 
ron) with tho fuct that immunity inny he of great 
duration, onct that it may be eonferred by the 

injection of Ific killed liActcfia» or. m ecmc cn«s, 
of thoir non-living solabid produdfi. 

&[dchiukofr mav be credited vntli haviug first 
offoreil u plauBtblo explanation of ntt-tnm! rcaiKt- 
nnc9j foutiifrfl on ohiscri-ntion. A* n roologist hp 
had etndicd tlie eubject of intracdIuUr dii:o*lion 
in Cho lo««r onimalft. and it vra« vhilo working on 
thift problem that be obfvirvcd the- ffitr nf n jcut 
fun^ne (Jicno^p^ra), rhich CAQHd opidcmice 
among the r^jiphnin. ^mall. transparent animals 
with which hr w« working. Nenr the (ilimenUrj 
tractt whieh wju tli^ Infection nlriom, tomo krgc 
mcsoblflslic cells, vliieh are |Kir)tapfl analogous to 
tb^ vbite blood colU, were oees to insist the para- 
fltac and disnolva thom. If this took plnoti to ft 
aoflicient ealent tli* ^imab recovered; if, havc- 
ovcTf ihc infculinjc orFranivros were too ntinicTOiu 
or tbe Traction on tho part of tho amnnftl iiunffl- 
dcDt, tlic body lieainc* oT**rwhdm>'il with pnth- 
tltca and death recited. Since that time Metcb- 
Ri|:<ifr haa ptciIvihI bin wiJI-ktiown throrj nf pbn- 
focTtorls as the ciaontiai factor id boUi natural 
md acqnirod immunityt a theory which Paateur, 
In hia later yearf. looked on with favor. We lauy 
apeak of thia w tltc cellular tboory of immunity; 
a theory which baa had to imddrgo important 
tnndifntionfi in nrdin- in hring it inlo accord with 
new facta* 

Coiuidering tbat tkfttural or ncquirod immunity 
cnuat eviiit becaiua of oertaEa qtTnlitie^of the brxly 
ccUtt or of the body iliiida, or poAaibly of both, 
iDTVtigatoTv bogdoi to ma^o analyaca of tba tis- 
Biica; and of all tbe atiaJ>«ea, that which we may 
terca the biolo^e haa bean tbe moat fruitful. In 
tfaiii caar hioSof^ic linnlvHis mc-iinK the detection of 

floii «if 4lit 


lit ««r*iiii*. 


IXJ^KVTIO\ A\t} fJ/l/rV/Tl', 


ivBdiiiiiM whUtli n\ny oi?cur vshen liru-b-riji or Uieir 
pnxjuctf arc phccrl in contiict with 1i«»ue ocl}e 
CFT flttJdtf, ('itli^r in tlie living animal or in tost- 
^hn expednienU. Tfie chief of tUew &re tlie de- 
tL'rminaUon of the nbllity of the »viiim of an uni- 
inn\ to kill bnWcm ar tn tiBUtrali^R fiiirlrria] 
toxitis. These important invest igation§ wei* in- 
nugurotod by the lindiugn of I'odor, Nultnlt, Ni<- 
H^, V, Bchrin^ ntnl Bwclinn'^ whicli fIiowwS 
thnt frc*h dctibrinatccl blood, and tlic blood 
flfviin nf variona aniinaU, ai'i* able to kill bat?- 
(t-rin in ihe reagent gln*j>. (n rontrant to th© 
action of ordinorj antifopti^f. this pow(>r tfi 
often WjJwrlive, killing one variety of baeterium 
and Icflvinjr anothw unharmed, Thia wa* of cnor- 
mons iirpoTtanoe, aa it m^mod lo idontify the 
foctor on wliioh natural antiljadorial iniiiuinit> 
d^caifi. Thpn followoil llio diacoTcry of Njsmo 
a&d V. Boliriiig {Vihrift mi'tt^hnihivi) , nnd of 
Bouebnrd (B^ pyocyctncti^)^ that if on animal it 
flyatoQiaticuily injoctoH, i, f„ immUDJKed, with d 
mior^j-urganiHin. the jowi^r of it* m^hjui tn kill 
tile bacterium u?cd in tho immunisation is ^^^tly 
incrcoHiK); from which it would *oem that acquired 
irnmnnit/ depends on the incrrcn«c of powci^ which 
are normally preaent to z. certain dogroo. These 
obKCrvationw hnva to do with the bac!«ricl<^al power 
of senim, 

Ft;rthcr progrcaa waa inado through tho diacov- 
oripB that tb* Ic^tjinu* buftlJiw (Brlt^tv and Friiii- 
M) end ilie tli|ihlhpriii bnrilluK (Itoiu and Yrr- 
ain) aecr^e each ft powerful, specific, wlublc toxin, 
whifh may be separated from the hactflria by til* 
traUon, iTnTniinitation wit!i theje batten um-freo 
tonus w&e und«r1«kaii {Bchrmit and Kita^ato, 

TO.TiAK i-Vii A^TIraXI^8. 


1S90) with the fficuliaf Tc»u1t of the pro^nctinn 
of the speciAo imlitoxiDS. Other iDvceligAtion» in 
this itir«(!tJoii nooa aliowftl Uie indtpenJence of 
Ibc juitiboctcria) and the nntit03:ic properties of 

Wttli tUaw ftttil« 10 han^, thn vigor with wMdi 
mvo0tigatioQ3 li&vc been pualieU may bo readily 
imngin^tL The hope nAtiLmUy prevnilcd that phy* 
fticbuia ]iiif:bt beconie the maaters of all iofcctmiu 
disoaece. throuf^h the poe^eEeioa of spooin^r nnti- 
bact^Pil Ajv\ aniitaxic M^itiniA. But failure with 
which wc arc only too familiar^ met the attempts 
to produee ailoqiiAle rtrtisenimfl for Tnany dineflBGB. 
KererUieleK* tlie?e failure?, tJirough stimulatinu 
to eloaor study, hitve rnsuliofl in th« Roi^umulntion 
of mueh adclitioual KDuwrleJge concerning the 
paihoi^cisie properties of differont b&utena. lh« 
lutni? of the immune fl^mnift and the various pro- 
tectiTO factoni of thL* E!ir)3i!li Jins evolved 
a new theory of immunity from fact* which wcto 
discotered in bis Iibi»rntory, the 'Mtle-cbain'' 
theory, which it ia the purpose to xitili^o in the 
interpfotnlJon of many rcActione wiiich will eome 
up for eonsideration. 

Wnjiht in Kri;;luad, Ntuffrld in (ir.rmnny, and 
H«kto«Ti in America more recently have led to a 
rr\ii»L [jf tntc7iT«t In iilia^'OtfylowiH nn n tmior in 
lutnral ancl acrinircd immunity, vkith th< reedl 
tlm thero oar fio longer e^ist any doubt ttmt pha- 
p^toiLift pla)* on important riMe in protmrtion 
ai;amat and in rtcovtty from many infections- 
Thnt !ho opfoninft of Wright, iind tho baeterio- 
tropiL* Hubeilvieea of Xt^uMiI^ bave served to bridge 
any <:haAm — ncT*r n real chnam — which aeemed to 
eibt bPtvre^n the fo-called humorBl and cellular 

JA'F*tT/«y ASD iliUUMTY. 

liuoTUs of immunih. T]it; ttudy nf opMtiiijit Jiaa 
alBO served to ttQ«v mtorcvt in d nmcJiDtiglccted 
field of spccifle prevention, narneU-, Jiwctcri*! vac- 
cioftlion, ono of the most ^rotifyiTig reeultd of 
which li&e been a letwm to tlie tut^rotilin therapy 

Howciver^ witti ull cur rciNourccfuliiuv, it U pw 
pible tlirtt onr limilatioiit mnj socm b? reached re- 
garding the eeruni and vftccinaE tliorapy of many 
infections, and we *hal! be fopcL'd to Irv other prin- 
ciplw of prevention ami t:urc. In i^onncctiiJ" with 
this pointy tho ne^vor eh o moth crapy, which hu 
been i^evelopecl in t^o brilli*iDt a iimnn^r by Khr- 
Ijch and othera in rolation to fr^paaoBamiaaiB, i* 
of tlie liipbest intert*st. It m&y he hoped tliat this 
work rcpreiKTitfl onlj the beginning of a ticw direc- 
tion of reficareh, which will be of ultimate value iti 
varioua bacterral an well a» |)rn1o»>an ii^feclinnti, 






P&rflfitism ia the ooodition in vhioh & plant, or rAiwiti**. 
AD iinimu] being, liv«i uti or wTIIjid unotlier living 
or^oisn^. A true pnrAait^ Alirays derirM iU sua- 
t^iancd from ihd tiBSiB(« of JU hoct. 

All inf<HTfiDiift Ofrt'Hw- is iWMx rthidi i* oiuh-'iI bj^ inrMTMAni 
Itring orf:nniPDis which in Bome wny hare entered 
the l>o^y, where they tjuilriply sTid liberate poUon- 
outt sulmlauci?*- Accordjiigly the woid hus rcfer- 
cii(T« to thv nnliirt! of tlifr oaute of thn difcns^r. It 
i* fi'om the T^tin utfUrrt^ meaning (o place In or 

Sctn^ pAraiitOA muj live on a hcv^^ without 
i-AU8ing njkj^rtK^iable daiiiHgt*; tliey An? rLUU'patlio- 
P^nic pnrnsitc^. In this ni9C th«y niAy dcriro 
i\w\f nutrition from aome *>f llie excreted ron^Hv- 
ing pivduE^ln of thi- ho»t. litiug n^ jitirn lutpra- 
phytVi' or tlic Amount of nutritioua flub«tAnco 
irhich tlicy obtAiM from Tbc host mif be no Iit(1« 
thAt tb« bt^AltlL *'t tie Ulti^r is not imp«ir«rl, ThU 
ifl Ira^ of orj^aniAma which nonually iahubit the 
inUcltnnI tracL 

prcptr coDdltlds* <tiiic[llu ef unJtfEJanl ■dDOA), Aad. oa 
dki aUHF hind. ■ p*lh<iv*nlr v«r«il1t llr^i t iiprapbytlc 
lllii, vlUD It ATom la 01a r ftrilflrU laKurr pntiB. 

ts^BOiioy xyo jj/jfUA'frr 



ivtmtfn II II d 

There U nnntlicr Ifir^c c]it<« nf phTAAitc*, hnw- 
over, which under proper ronditiona cftweo wtow 
(liKea^efi in the liostt Miin^ jiatliogeiiio iriii^robes )ivi? 
in mid en the «[ci]i am) inucoU!< mrmbrniic^ witJi- 
ont doinii Jinnn, hwt if o^rtnir on^ rpuch t^ic 
deeper tisbuee. Ihev may tiialituti^ paUiolo^'ic proc- 
eww {e, ff., utapUylococci. streptococci, pnyimiococ- 
4.*L diphtheria bncllli «nfl mcrLinfro<?ocpi). An\ on 
gnnisn whicli i» able to Cflu^c pniholoiric ti^^tie 
ctinjigi>t, to dishirb functiona> nnd to tiel up Ab- 
noriEiu] ja.VMi^rLuiuB U ula^ecU aa n paUii^yiuiJE: ^laiu* 
site. Tlic nbnonnnl proccfort which they iiutitufc 
Brt> oiir infrrlifiiiji dicoii«M_ 

Where certain coniimratively large organiirmfl 
fmucroparafrit&i) tvut on n body Mirfacc, u the 
.«kin <ir ]JitK'<fJmL] IrHct^ tfjf i:iufHiv (,« Hiiid to \tc 
infc#t«d: the Kkirir for txampk, is infc^k^ wHIi 
pedicvli. On& may fl1«o lay that the intcMirnT 
Iract is iijfcfilftl witli Upi-wonim. but hrm the di*' 
tin^tion behvrftn infc^tntit^n rmd iiircction is not to 
bp drnwii »;n Khnrply; Kurply whpii thp tarvn* [H'ur- 
trate the intcftinal ^ivall and rcath the circulation 
or dwtant orpinji uc muet speak yf inffiction. But 
evori lln' arltill. lenfa aa It o\iflt* in tb? inJe*Hnf'fi 
may cause crofiona of the miicou« nicmbrauc or 
may p^rhnp^ b^irrow a ^It^ht dii;taiioD into ttic 
vail- a conJiLicm wlileli approsiiualKa tlie action of 
the larviT in po^^iuff throuttli the wall; necordingly 
at some pc^nl the ijittiriction h&tff^en infedation 
und iiifrclintL brrtiiiK'* nti nibilrary our. 

The known palhoj^cnic micro-organism p &x^i 
grouped oiiioun Ihft funsi, tho bactorln and the pro- 
toion, Dolh the hactfrin nnd fniiyi artj rentable 
in nature, comple-xity in form and methods of 
growth chararlerizing the latter, vherra» the life 

BAVfEiUA A\n rnoTom.i, 


huliijy o£ thf fornirr in fimpfcr. ami thf^y mulli- 
ply only by fienioii (fisiion fuD^i). Fonna occur 
wKifti nj>j>f*nr in hp \^^tt*^^^r^^)^i{e ljrtw*en Uin true 
fongt and Ihe true bQcleris. The protoeoa, the 
l«WMt forms of uiirrifi] lifo, vnrv prently m form 
■nd in JJic oii(rijili*Kitj uf llit-ir lift' ejdes. TTie 
hif^t jirotozoft kad an iotricflte txiatence in 
which tcjcofllit)' 01)4 AltcnmtioTi of IioeU urt^ aomc^ 
ifpi^a compictioiu feflturefi^ na m the cafie of the 
paiaBit«< of uialario) ferere, and possibly in ttist of 
}rcIIov fc%xr. In eomc LnvlAiiocA tbc alternation 
of host* U purely a facniiattve prop«rt\\ find not a 
nfcnaiitjr for tlio jicrpctuntion of tJje spede*, al- 
tlwujfli il i« pftrt of tbc natural cycle: this ia the 
COM irjth eonie of 1L« trypanoeomes, vrhich can be 
IranKfirrrd from animal id uiiininl ai'Lifii»nlly f»r 
ftn indvfinitt; period. 

There arc certain infoL-tJonA, tho cnusos of vhich 
ar^ not known, iimt in »omi* iiulaiK'ei tbt* orj^aii- 
timh are uuti!»iUcitiI a^ ulLi'aTuicroK'opiL: becziuw! 
they paes Uirouich bacUrlclo^io Ultors. 'J'hoorctic- 
ally they may bo ^it)ivr bnctoriii or protr>;con. 

Tho known imtliogeiiic micvO'OrjjHJi[«ma may 
nUo be placed in one of the follo^nng thre? groLips ; 
1. Obii;>iitc paraaitcj, which urc capable of growth 
only in a living organism (the biicinn^ of leprosy 
ajid the OTganisTn.i of malaria}, S. Pnc;]lt«tivc 
»apropbytaf, vhich ueually ciist na purasitcs but 
may loultiply on innnimftte tnatensl iLnder proper 
txuidiiimis. Tliis irnjup iiirlinW rn^nL uS t>io pat!]- 
OfCnic niicioparatUc?^ 3- Facultatire paraeitc^T 
wMch are laprophytic or^ani^ini living veadily on 
inanunatc tnati^rial. but Khit:h may produce di*- 
Mficr when thei- rvach AuitAblc tieeiK^ in a ho;t 


Orlrlii an4 

ixrBCTios AND tiiJtvxny, 

{Baciilm uicni, bflcillii« of maligaa&i edvnui, 

H ie futile to dpofiuJAte on tbe ultimate origin of 
irinr mmutt micro-OTKiuiunnB. It U AtifTidont to 
u|>|fTrfiiil<* thflt the principle* 0/ biolo^ and evola- 
tiun ar^ broad enough to pcmiit us to naFkiimo that 
ftOfrfl iif tlje rt|*eci** wtrk'h we now roeo^^iii/e may 
have ariflcn Uiroiigh tlic iciJtuciici:^ cif cnvironaioat 
nod wilection frnm i)lhpr tnoTf* nr 1?** doeely po- 
Ifttcd fpccic^. HouevtT* ioi^ati gallons have tbown 
that th« e^erttial clmrnctcrd of bacterial specks an 
fiKerl rutin* (ir !«« nrmlv, nu^'^TUittitg tbjit ttvw spc- 
c^uA am likely li> bp developed only tlirmigh a hug 
iroiirpB*? of time, or. if more <^iiickly, through rare 
rharkce variatioQ^. Koch Uaa ^u^eetcd thai airiong 
ihi> ujpaoosomfia found in difTeroit dUcaBce some 
iixuy ttill W too ymin^ In thrir dilTrrt^nfifltinn 10 
roproMnt fixed epeciefl, nlthou^h this cannot a|iply 
to the whole group of ti^'pancidomc 

Mflnj micro-orgnniftm'iL fin, indewl, ^how a great. 
d^al of flenibilitj \n their pliy[i(o]ofe7 and virii- 
l«nc«. with tho rcfult that tliey mcj flpjiroitimflt* 
Hp«ci(^ which are ui^imTly nH^Of^iii^Lfl hk bf-iug dl^ 
tinct Thus a strain of the diphtheria bflcilln^ 
which Io«^ iU ^'iruleiLCu le BimiUr to a p(icudo> 
iltpUthmjL liaHlhtfi, nm] the rhnlrru wibriu rthU'h 
h&A b«conie avJnilerit reaLvnbles d ciambor of other 
vibriofi, Tbo \t\affui> Ucillut, whenA» ft conuoonty 
c»ii4e9 scirte denth in rat§, nia^ undergo «fjch a 
<haiijri: ill the clmTCtttr of its vinjluncc that it 
CA»«o« a chronic? nodidiir inAammation^ Som^ 
Ktcaiiift of the letauua baoillus. which i* iialHiurtllj 
fluoflrobic, nccniir^r the power of growiiiif Iti the 
pr4!4enee of fltmcwphfri"* OKVgen. By Huitable 
paun^ a jjiecleji-of tbe tubercle bacillus riaj; he 

VAfiHSTifOi or OXilAXtSJt&. 


Fuidit to rciemblc T^iry oloidy In itf cuitur«J ii»- 
prt"U ani>ii]cr *i>eiMt* of t!ii» oripinisrn. On tfie 
whole, tliose Arc nnt laTffe Tariations ^nd idontifi- 
cfltion can be acconipli»hed by one or more of the 
biolofic re^tioQii, snch at» the agglutination, bac 
twiol^tic «r opwnic 1*«ts. 

In iome irt«tjrio«4 lli<i t'ondiljonit are ^ch liiat 
diflcrcnt iip«i(5» oppcur ta rcfrrsrnt onlv diJfcr- 
oat grad«« or tyj^^^ of vtru1enci> nf the same or- 
ganism' ThD«e ucid-fa»t bacilli which rB&i>mble 
the bacUlufl of luberouloilfi form tJie moBt fltnkinjj 
example of Ihi*- Ri4f?i]li of (hi* charai't(?r ore (Dm* 
monly fou&d in rariciig jrft"»« or clover, vhich 
are lu&d b« food br pflttlo. ^iich or^ani^ms linve 
a low grade of virulence, jjnd when iujeijt«*i) tiiUt 
animals <?ause Xht^ fi>nnatioii of only a nodule of 
gmnoktion timtrn^ wmictini™ with ihe prmipufe 
of ifiant c^lU. flnd the procew ho&l> readily. It is 
poeQilile that certain of these organiBniA of more 
Uian *iflu«l vinilt-mt"-. or which miiy hnvi* acquirnd 
Mch Tiraicnr^ by residence in the fllimectary trflcl 
of the ox. have retained their ncv^ patho^^ntt? 
power an a prxmum-nt charBctrr, nml that bovine 
tubcrculofif oriirinatcd in thie way. It weald he 
nattt the leu loptic-al to aA«unw dmt Llio haeillun 
of human liiberculQ^iii wap d*rivet] from tlie bo- 
vine type in a mimUr thuuhcp. Thii i-au only be 
)i suhjivl for tpcrulvliun, htm'e\-^r, 

BjicteriologitftA fxequeiiDy tie a\Av to p]ac:c a 
number ol wp^itB in a '^t^oixp," tho nicmF>crft of 
*bii^ r4i«embl(* f-arh othrr morp or le* oIospIv, ah 
thf colon group, or Die dy^tntery fjroup. The 
momberK of a group may vai^' niddy in their 
pfltbogoiic power, whereas in other jni<tan(?e» th«y 
produce eimilar dieeaw^ 'i'hm, Novy hm ihovrn 



/.vrffCT/OA' .iy^& lifMCXiTY. 




tTinl, nllhough tli« tpirilliL vliich cause tho various 
rwlmpj^mg rc\-<»rs »f<» very tiinilarr they can lie liif- 
forcatiatcd by rucuDf or immunitv iceciions, «uch 
aj4 the flggluUnaliug ur prol^*tiv4r puvvn of im- 
mune acTuniK. 

A more detailed diecuMion of th^fl aspect of 
general lMclm«lo^v would ciiirv im tou far flflrld. 

Confusion stimctimca ariiics ronccrning tb« fig- 
riiflmnr^ of Lh^ vronU infoc^tious and contagtom 
and othev woid^ liaviDg aijiiilar roots, 11il» raa- 
fueioa is due in largt part lo the fact thnt they 
Imie ^rowti iiiLu u ^aia^i? viirying nomewhat frofn 
thftt whidi oripnollr B*^liered to tljonu and tlie 
(lif^ti*mHHe*, even those whirh are medieal in ohnr- 
adf['. liave hardlj kei»L pace wiLli lli« trannitinn. 

'I'hc a^jrnificnnec of UifrciiotiA h indioaltd »n the 
dellnition of an infeetfoue dieeaeo as ^vimi nttovt-. 
Tlic vord foniaffiou^. <m the citlirr lmn<l, relal** 
to a raflthod Ly which some of tlie irif**ctioue dm- 
(."a^L^a ur-i! ([■amtmittivl from iiii itifrHM person or 
animal to Uie bealtJiy. namel/, contact, dirwit or 
indirect. Not all Infectiont are troiwrnittcd bv 
cortect. however, lienea we nav divide them into 
those v}iieh anr eontn^ticjiiti and thu^ trhTeh nn; 
not. Commnni'^abk ie oftoD it£oc1 as G^nonymoua 
with rnntrifCifiirH, 

Coui\i^ioisBTiv>tt i» all the more striking in the 
ciM of a<;\tU infeclion* wldeh d*v?lop rflpidly nrn! 
soon niier oxpit^iirt^. On the oilier haml^ It w iint 
80 stnkinf; in a dheaso fiiich && pulmonAry tuber- 
culoitK. u-iiieh develops ^loukly jind fierhapi only 
after rcpTAted eTposurfi3. 

The following tatljer ^neml Hi-rftugempnt of 
the infi-elioiis discHi^f^ ifito groups aeroriling to 
the methods, aacl at the same time fBcilit>v of 


DJS8£Ali:iATI0?i Of OROAyiSHS 


trnTi^miwion w givtn in or3er to illu&trate ttjc 

1. Tliciae wliicli are cliaratteri^i^d l*j rendy tnin*- HiMW'rii ""^ 
mjAiMoc tlirou^h ilic air. Tht inicro-organismf are 'ri-nn -«*-•(«■, 
dlfchni]^ into tho nSr from the rctplrotory 
posmgiw, ni- from tho *kin in d«finnm^ti»ft fnfof- 
ti^iu> Bnd il if only noccft=ary for c 6ii^coj>tible 
ptrsfjn fi> Lt>me M'ithin iJie 2<:*ije [>f ir»fectL-il hIi 
which surroiinds th<f paticrt in ordf^r to Mc<iuirt 
th^ cliiviu<>, Actt)«l conlnct with tlic pativnl may 
facilitate trantMii^^iua iu eoiiie instaiiceK but is 
not ntccEfiflTy, and many of them ar^^ li-Anamitlud 
hx inAiT^cl fOTitftft, l.e^ tliroiiffh t>it» Bj^cnc^y of 
iutennodiate pereonf, tlirough fiMxl contfiminatiou 
(scarlet f*T*r in milkl, cr through inanimale sul- 
>tsnec3i whMi Knv** l^n*!! in tiiiibirt with tlir pn- 
ticDt- Thcflc arc oil hifiJilv cortnjjm? "oir-br»mc'* 
dimoMt which probably tise Hit iwpiratory pas- 
M^ee Bs their iufcctlou alrttiiu. Diphtheria, *car- 
Itl ttvtr. meo&lcd. rolhein, nmanpoi, infuciiKa, tu- 
IvimhiMR, vnil pUgiip in ph^m prifiimnniii htc of 
thie typo. 

8- I'^tc^mieajon occurs almost exdiisi**ely h\ 
prr««n»l oontnet. (ind unmUy a *peerfl! form of 
contact, nevtr lbrciie:h the air: ^aorrhea, ^yph- 
Hi?, soft rhaiirr«, and p?rhnpe doarine in horsM, 
SvphilL* ucva3io:iHlU u IrajiBiinlW hv iinlini.'t 
c03it«ct, the free l^^riod beinj; a nhort one. The»e 
«re ctmUgioiiK d)»n«^- 

3. Trannnbsion i^ chiefly hjr iTidireet conlaet, tMilI^i' 
or through food or water. IKred contact play* a 
t6Jo in come iiutaueci, and rar4]y tbo air may be 
a uuanK of convevance. The members of fhia 
IfTOup «te Dot highly contagions in the sonK of 
tranfiniMton dirertlv from one in6Mdual to anoth- 

typSCTIOS jyO iiiliVMTY. 


Vol Tmn«4 

er. The niipr<»-orgiin]>mK nne eifrpte*! muinly by 
tbe f«c§^ anj typhoid and ptratjpboid by th* 
urine. Afl a rul^* they are acquired mdinctly, as 
throvgli a wale:' suppljr or milk which hare bcm 
infected from discharge rarLtnininQtif>M of tbe 
bunds from the cxorrla tn 'ood Kxuniplr^ are tv- 
phoid. paralvphoid, clioEeia and dyienten'. 

A. l^aneinisaiou by lueajift of tnaecU. 8om« of 
these diseasw, as mBlatia, jdlow f«rcr, nml Rocky 
Mountain spotted f^ver^ arc oot cont^ipkua at all, 
but AFQ nevdrth»](«« communicable through the 
mcdmiii of tl^e |>roi>«r iiihvc-l. nioer|iiitoe» or Ui-k«, 
SrtuUi African tick f«ver, ordinary rrljipsing fever, 
pla^e ill tonia inatancK, trypan o««miflsi4, And 
probably typhos fire otJirr cxaniplee, T!te *l*p» 
in Iraimninaion ar? ^omctime^ very com|jtG\, aad 
vaiy A great deal, nn will lie ixjintral inii Ulor 

^- 'iVauttnuiuLon frmii man tu man do«a not 
take pluce at alt under ordmnry vonditioiu: tet- 
nnns, ljyfrn[>]inlfi^4, :iniT other wixinc] infi?i'tionii, 

U is. tliUA it^ati Uiat thi^e Hvt? diviBiona coti^ti- 
tutc a ieriea in which t-onUgibuinus* I'lnally disap- 
pt-ari- TliD flubject of tranaiaisaion will r^fivc 
fnrl.hffr con^dorotion hler, 

ft. hrts hflpn Blatcii iiboA'e that inferlJoiw diaea^ae 
arc caused by living patliogcnic orgum«inE, In- 
vf'itigationft have shown, however, that the toxio 
products of some orginiama can be prepared and 
nparalcd frnm the orjfanipme tbeTuscli'Cs by tiltrA' 
tion. ami ihftt such it lio robe-free (oxius wb*n in- 
jcctcrJ into jiiiimain mny oausc tlic sumo symptomfl 
that ftTo proilucod by l^e bacCerii themaolvcs (tota- 
nus and diplitberja). Accordingly, for the sake of 
convenience, lbc-<c loxinai aifro may bo coEsiderod 
among the infirllnua n^nts, (von though sopa* 

VLASVIFWATtOX ^y njeoisisMs. 


mltfd Inmi Uieir wirreepomiiiig bfl.eti?nd. Tin* va* 
viou» infcctioiu Barents, including thfi«c toiin^, lind 
(h«ir proper pkooe in tlo folloiving clansifiwitioTi, 
uhii^Ii. for Ulc iDcifl [jait. 1^ Ihiit tjf vuu Deliting 

I, liiTinf (i. c,, pxUirJgi^iiic piu-AHileif)^ 

A. M<crt>paTaaitc« (c g*. intc«tmal worms^ 

pedicuti iilariiP: uDcinarin). 
ft, MicropnriiMte*. 

1. ^nctcrla (fieeion fim^ ; cooh cell di- 

vld«t foto tvo in pT0lif«TatlDg). 
& Fungi of tnore complex orj^fimzation 
{e. g.. tapetfiflb^f oidia). 

3. ProtoTiou {k>. pj,, Flii/tmotiium ruafa- 
nVr. Aniir&<i ci>;i), 

4. Filterable. iiltrftmicroMiopic nv xin 
known micro-nrgnniftma. 

II, Noc-liTinff (i. t, toxirii). 

A. Acitnn) toune (e. g,, oinkc venom). 
Ve^faMe toxins 

1. Non-bactcrifll (c. ;., nbrtD, from the 
joqiimly bi?an; ririn. from the cae^ 
tor oil bean; the toxiuK of hnv 


Soluble bac(«ritil ioxias (diph- 
thcrin fln/l t^rtitnn?). 
Iitlni<-ellular bd'.'Lvrial dixiot^ 
which arc not iwcrrtcd fay the 
colU in a tolablo form. 
In the aubjtcla tij le coDa^dcrnl kc *hall d?al 
6h]e6j Titb i»icropaTUHjtc« and the rlif<casc-ii wbicli 


i.vfKcr/ov JVD rustvMTf. 


K»rli^* l.avfh. 


U i« cvifJvnt that tlio liiicoverr of \he eppctfic 
oi^nii^i of an infectious diseo^ ia of tbc ^crcat- 
e^t iTti|K]iiAnre for |iurposos of i«nim tLcrAjsy. vuc- 
ciiiation artd lij^iuiic pTcvciitic^n. For tlic dcnion- 
ttraUoii of H vini», \i \* not in nil ca«^f n^ei^nn', 
thcujgb (lt«ijaMe, tliot tlie oigjini^in l»e <'uUivateil 
artifleially, n^r tlint it be recoKnixccl vijunllrH The 
conditions in nnd(?ri>&&t may bo died in which the 
IhkIv fluids ijT n ilisriWfvl miimtil, kmiwi; ia wnitma 
Ihc mfectioiid a^jont, an^ ucud for imiuuniiation. 
alUiovigh Ihc mi^^rgbc it«clf cun not at j-ct bo cuUi- 
i-nted m- recugniMJ. 

Tiicce are ski many poftaiblHtieii of error, and so 
many error* hove actuolJ/ boon mtidc iu rugnrd to 
infcoUoui etiology, that cortain reqiiirenienlj* in 
the way of proof are now hnbit^ifllly dcmnndcd be- 
fore n |>urlicuEar orjpinirLm can br ucecpt^l aa tlio 
cuixsQ of u diicaio. These reqiiiromfpnU are moat 
fn*£|iii'-nfTy rxprr^wil in the form of Koi-h's laws, 
which may be atfitcd a& follows 3. The suspected 
orf^iiB;m rauut b9 fouiu! coiutunUy in th« proper 
t.ie8U06 of an animal tiulTfrm^ from Ihe disease, or 
which has died from it. 2. The orgAnism must be 
cuUivnled artifieiaUy in a pure stale, '■^. It muet 
be jiossiblu In reproi!iU'<T Ijic disense in n niiitabk 
animal by inocniatiou vith Iho pure ctiltnrc* 4- 
Tho organigro must again bo cukivatetl in a pure 
vlate from Ihe tfnaueei of the eiperlmciit animnl. 

KOVli'ti LXW6. 


SiiK« tJ)we Uwa ware formulated Another prooo- AKsiaiinn' 
dure has Wn evohtHl ^t'lik-li tiia^ giv^ valiLabl*: 
evidence no to otioto;;/. Thm [)crtaiii0 to ttie ng- 
ghitinofion tci^t, or, ae wo cpeiik of it m CL^uiiection 
witii typhoid fcvci\ the Gn»bcMVi(]*il reaction, 
TiuB principle, that in tlio Acquiring of jmriiinity 
•ta a microbit? irifeotinu llii* «;eri]fn of ill JridlvrTlual 
gnin? in jiggUilintitins power for tho micro-organ- 
ttm, hfls Unm found to hold Iruo in mnny infoo- 
■tiona^ Conscqucntljp', if one hub m Land the spcci- 
ffic rniero-orj^anisoj for a ilJMafie^ ho would ©xp*ct 
Ihi? u-rum of ii patii-iit nick tif lliin tli^iTauL* lo hnw a 
(trongrr ocglutinating power for this microor- 

miam Ibfln for nth?r« which were ncoid^ntftllT 
it; lUid UiiH powiT would alnj bi- ^-n'^il^H" llim 
mt potaKfTCcJ by tho Bcrum of one wtio had ool 
hurt thifl pwrtfciiiar disi*MM'- In spiln of KnniP pc>s- 
MbiliticA of error the Agglutination teat liaa bocn 
of diBlinot value in tie rccognitioD of tbe Bpcdfle 
rJniffrv-or^nniflmM id coitniii diw«»«*, ns in tlic Cflsie 
'of tbo |:cnn of cpidomic tly!icnt*^ry (8hi^) . 

AIm the moi-rt rwcnt dc^vc^IoprTicnt of tlie op*o* 
nins and. |inHi^*iiIarlr, of the plienonTcnon oF fiitn* 
tiott of comp1<:Tncnt. promi^ to be of valvio in the 
ipiilion of »[K*r:jfic inii-ro-OTj^aiLiiirin, 

All Koch'a law^i liave not been complied nitii in oLkmoi 
certain «!aM*, becansc nt rnriomi ditliciiEtiCA 
rhich have bivn <5ifonnIi?r(*d- Final, tbe pnlbo* 

lie YfolomA can not le cuUivatsd on artificial 
media (vt muAt OJceQ|)t tho aticooia of Novy and 
M^^Ncil wilh (vilnin trypnoonnm**, and of Mn^ 
jnuT and Olpge witli (hr ^nurfto <oU under *vra- 

ilic condilionp) : second, certain bacteria which 
my be found ccUhluntly in n piven dlieaM hnva 
Itfrt b»in cultivated arliftcially (spirillum of recur- 


nrpt-no* i^o iiuirv/Tr 

rcQt frrvcr) : tliird, thet« are u few duMwc«« which 
ar? pM>t]liar to m^n nu^ occordtcjciy c«n not be re- 
pro(h/n<?d in dprrimi'-nt Brim:ils (leprosy, scarlet 
fever, mwiolcfi, etc.) ; fourth, some mfectioas agcatA 
nn> pqthogi^iiJc for experim^iit animals, but do DOt 
reproduce in thcrn a cliDicii] or anAtomic conditioD 
identical with thnt found in the oH^cal animal 
(typhoid ) , 

rurUiennori3. fnilifre to comply with nit tht n* 
quiromentd eDumerated doe* not, in aomc casu, 
disqualify tli4 orgEoiiem aa the caueal factor. If 
nti oTgnxiitim is foanl rnn^iUntly in dumictfTriitlic 
AJtes in a given diaeaae auil not iu otber iufdctioDa. 
aod if at the same time other micrcbot are not 
proaenl or are preaont int-onatantly or throu^ a^* 
udent, there coultt be little or no hesitation in bc- 
coptin^ thia orj^oniani oa the cansc of tho diiooao^ 
OTta if it vcrt* impoaaible to onltivate it or to trao^ 
far the rlisoHae to animals, The typhoid hacilluH 
haa bcoD cultivutcct from churactcriatic foci (.stools, 
blood, ttpleeo, url&e, roee fcpot«) in such a large 
nnmbcT rf cases, and the hadpHHclal nml agglu- 
timLting jhiwcis of the putieut^ Kcnim a^^aiikst thb 
opgauiam are so dialinctivo. that compliance irith 
tlio tliir<! lav, though rlesirabla, i« not now essen- 
tial. Th^ condition?) are eiinilar in referent^e to 
cholurn nnd the cholera vil>no- 

The conditions are ao nnj^ae in snme UieooaM 
tbat, nUHongh all Kfjcli"*! laws have not beea met 
litcralty, certtin equivalents Iiiltc Iteca met. Ti> 
illuatrfltc, we may consider an anopliclcfi moeqaito 
whidi UftB become infected witli the plixsmodium 
of malaria by biting a malarial patient, as a cul* 
t«ure modinm ; and the tranaferring of the infection 

tXrtSVTJOVS itttiHAdBl^. 


u> anothor pnti^t bf the bite of thie tnoaqcito m 
ihic inociilatifiii (*3cp«r]inf*nt wliich ia d^irei!. 

Thn term '"^jHiJOrifii: iitfi^lmuH (liseasu** has come •p**-iflf 
lo have « very special moaniEkg, It is applied to n i>i*va»ii 
discac<r having charActorittit; clinlc^il fto^J aDatomic 
pbeDOmeDa, vrliit.'U can be uauHeil i>a]y hy one jmr- 
tjenlar micro-orgitnifliD. Among the diseases 
vliicfc come villiin Uiu limiU of this brief dedni- 
tion, the following iriay be enumerated (ihe micro- 
OT^izusm which i» the caii«c of crkch diccaac being 
also given], for the aak* of lUufltratiou, 

Trpboid fever 



Dywnlflry (bacillary) 
Glim<I«r» (farcy) 


BMurrcnt fev^r 

Bpidomic cCTcbivdpi* 
nal men instill 





BGciUuii diphthmiB 
HocUIks Utani 
Bacillus typhosus 
Vihfia chuterit 

BcciUtii tuber cuIofU 
BcalUs lepra 
Bcdilus p/>sli» 

Bacillus injtutntcj 
Baciilui m^ilei 
Bacillu* chanrri molUif 

J^pinittirtt obfrrnfitri 
MierocQiXus f^^ri^rrh'X.u 
DipJccoccus iR^ractiIul<t' 

n> me tt'iiyjiiifi lit (of 

Artinomfjms ftoMiV vf 

BtastotnytfitM and Oidia 
Plasmodium maiana 
8pir»chata paUid^ 


lyyEcrioy ^yu ruMuytrr. 


A tdrgo number of ivnimni discnses hnre ihtlt 
epflcific microbof, lu d*> certain other humnQ dU- 
CHsen which liardly concern tia as to the siibjwt id 
i'«uiftdv.i. In ft^lililion to the disefl&ss montionod, thftr^ art 
Hevei'ul, of uakitown etiology, which trout auabgy 
vrc muttt recognize as entities beca^K: of their coa* 
fiUiit Hiniri]! and Anatomioa] m^inirr^Rtationii, Str- 
ict fcvi.T, uienfilfSr German measles, ddckenpor, 
8ma)lpoi. yellow iever, typhna fever and hydw- 
]>Iiubi]L. iiri; uudnubtvdij' due to mUru-iirgniiif^m^i, 
Mollory rccprtly found in the flkin of four scar- 
let {t!vi>r pilipnt* ft prf^to^f^rtn-liko hofly which h* 
bciicvcp to be the cause of the disease, al though 
be ndmitd that miich deeired proof has not been ob- 

It is po»ible tliAt amdllpo}: Aud vaccinia wDl b« 
eliminntt^d from tho clisi^nsoa of unknown cania- 
X]ou^ nwing to lli^ evidence of |)]oto/fMin Kiojnpy 
tluit Councilman and bh cobWurs have obtained ; 
howovctj for the present, tho qiiflslifin it stub jndice 
in vie^v of thi^ fact that the torias described bear a 
doee reaotnljlauee to certain well-known types of 
eeJI dcKi^netfltion. 

Tlje following aninial ilipeasa*, of unknown 
otio]o;->% may alan ht« mentioned in this connota- 
tinn: Ffmt Jind imiutli dtsensc. peripnyumnriiji, 
borimo pest, »hocp-po\ lclnvc!cc)> diickcn-typhua 
or chick^-p«8t and epithelioma contAgioenm of 

The following appcor to be the chief reasons for 
the fallme to discover ihe organisms of tlw^e dia- 
oaics: 1. Tnftbility io cnltiviile thf microbe. 2, 
Mbted, or (lymbiotic mfpctiors, l-Vr n long tirnc it 
WAA supposed tliAt the &o-called hog-chulera hacil!u« 

gpEcfricnr of vjtQAXiaMs, 


H the Mine of lioff cho}cTt. U^ent eipf?nmenb. 
howrcr, hiTc dinclcrtcd that Iho tnir virur; ik ullra> 
microwopir ami fllteraM^, the havWUt* hein'^ onli 
a mora <'r 1»« consUut a&«ociQt4^. It 't$ conceivatilt 
tti^t hi tOQi« caae» Uic conibbi<4 Action of two 
mirro-orjfAnijimji majr be Decenary to cnusn the 
disoaeo, Tho nr>ii-t>xic protiucte of tho IM'o mny 
B\'n(tic-^}:c tc form n loxic mmI)^^^^^ {Hekl;oen.) 3, 
I'lirtniimbiLity of the microbe. 4. Liltramicro- 
•oopio ftiao. Tho orgitniem of the peripneumonia of. 
cattlv Wrts cuUivatett by Nocard ajid Roua by grow* 
iup it in ft cioW collodion sac which was pluocd in 
thp pi-ritotw"i»! rjivity of kLtittnhk* [uiimtils. It \t so 
atnAll that it* form cnn not be made onL and 
growth is rocognizod only by clouding of tho 
ntttum triuilEuiu. ami tltr iucreHftstl virulence nf the 
Inttcr for nnimntsw 

Somv \^]nnb1« infonnstion baa heen obtaiood 
by oUuTviiiK irli<!llirr tfm in f f ftioiis agents luc 
90 smjill IhAt they will pUM Ihrou^i dcnso filtcrv 
of porcelain or infnsorinl earth. It (la^ been fmind 
tint tbo TirUfiCd of foot Jind mouth diaeueo, peri- 
piUMunoaUr rinderpoat, shcep-pox, ohiokcn-typhns, 
home r>Kkfios», opitbclioma cunUglofiitm of fowla, 
yellow fever, hydrophobia, and l^o^ chok-ra are fil- 
tonUilo. Tliii i« (letemiicod by injcvlJnp the f\\- 
tared cflltnK medium or wrvim into susceptible 
aniitiotB. Tf^^ vinjee^ of imftllpox, Tnccinia. and 
Jtncky Mountuin H|]oIIo^ fev^r an^ not filLi*rabl^. 
Inaaiunrh iia wirlct frvcr, mcn.ilc5. chicken-pox 
and tvpbiiK frvpv ennnot ho frr\dn^■'^d in ftnii&alfi. 
tl>r lild-iiiliilit't uf their viruH^ U nai nt promDl 
fltnccptibk to determination. 

ThcTO is n siArkod tondcccii' in many diAoaAtt, 
hrpihotd. cholera, irtalflriji, etc.. for cbarActetietic 


OTgaue or groupi; of organs to be involved in flom<r 
particiilnr mnnxi^r The»e nre foatun^ vhieh. 
togetlicr ^xilli 11 i!i>iL»t4»t Li(u:t(^jii!ci|£V, Atainp Uiom 
03 fpccifi? diac&fce. On the olAor liand> a hrgt 
niunber of micro- ur^rAnUiru caum no w«U-d«tu]««I 
clinical and anatooilc di^cate, but. d«peudui^ on 
rorioiu accidents, CAUttc an iuflaimnatign now in 
OTK» organ, nnvt in niiothtrr. 

B^^rdJiig llie prculuctioo of ^itppurAtion. tU« 
pyt>pi?njc pow<;r u cuninion to a lar^f nuuib/?r 
of mkmbeM. A diijIillitfriLIc ur psvudD-iliphlWi- 
tic pTOiXfla in the mouth und throat may be ceiucd 
by the diphtheria bacilhis, alreptococcois, ataphylo- 
C0CCU.4, oiitium or jt^ntctA ; bratii^bitin xiiay lie ciLUncd 
by the influ^ns^a, luberde. pl«|pio and typhoid 
bacilli* and bv thi) iiifacting agentfi of tho acute 
ntnnflu'tmUiiT aUu; pulinDiutis by tlje putfumoco^ 
Ru*, atroptococcufl» tubercle, plague. Fricdlander 
and inBuonsa bacilli, oidium, actinomyceSf etc.; 
meningiUii by iha tnbetcb luid mfluenza bacillf, 
klrcptocoa^uti, [itaphylotzcKMus. pneumormviis. gono- 
coccuB. diplococcue of epidemic meniugiti*. the 
dyphilie virus, otc, ; artbriti* by tlio ftrcptficoccus, 
ntnpliylocoHWiiR. tnho-rf-U* hurilln*, ;fonoerM'(?uc, tho 
vinui of rhcnnmlir ffjvcr, etc,; erw3o«irdilin by tbft 
*t«ptoco<x:ua, stapiiylococcufl, gonococcua. puea- 
raoflooeu*, tubercle baoillue, eto,. xnd tepticomia 
by a whole hoet of org*ni*nis neide from tJiose 
mentioned na oflUKing specific disT-anf^B. 

Within eerUin limita, Jiowerer. tli«te is oflen a 
degreo of epccificity in tbc processes produced by 
aomo of tbe orgoniamt mi^ntioiieJ, whieh aomft- 
timuiA ullowjt uT i-IiiLK'ul niid unHtoinic difTorentia- 
lio». Th« inflltTating and ropidly c^ctcndlng in- 



iMMD af Uic tfubcutooecma and cr>nn«cbTe ti«.'^B«e 
cavMd hj tbo ittn^pioc<M>ciis ^an often be distiit' 
guiBbfrd clink^y frotn the dlonci. nt<>re ciraim^ 
ecn&ed proco* oauwd by the Ht«phvlix.i»L-ouB, Tht' 
cmidrtitale inilntvvl hj Ihi^ HatiHuit nrru^mts rMjt- 
thicita^ the bociJlu» of malignant ^cma, arc> in 
tura, tlilTcM^t from t!>c«e of the rtrefjto&xetiB luwl 
staptijlococcuft. Tlie pnetirnococoiis oomiiiotili 
caiiMS tbt con^lidalion of rather ext^nsWo arcar 
of the luiif. ^ltcT«<£ the etrcptocoeeuit find the 
hAcitlna of Frie»tl*iider nrp more often fonnd in 
the Inbaltr roniitiliilu lions. Hie inmil>nuioU:i in- 
lamination of diplitticria itm> in favorable oaaee 
!>• ji«lln^ii^ht>d from that of the pyogenic organ- 
JMT» williout WU-'rioki^ic tttiJti ; in thin |NRoil»tHty» 
bev«T«T. there )ic« no jiiBtifl<-ation for ne^l^ct of 
tlift I>actorio1o[nc cxaminntioin. 

Tn niitunr pntltogpnic mIm>orgatLi«»« arr oftvn f|,„kiii 
fwind acle bj side nitli aaprophyttf or with other 
patho^mic bortcria. nnd at timea their viabilitr is 
profoundlr inHuonow! by their aaiocSat:!*. Thtis 
it is found tlint Ihi^ hai'tlli of plague and lyplioid 
and the Tihrio f*f cholcrn do not lire long in tho 
!Mncc of many sapropbtli^^ organism*. In some 
tfaii<^ Ihifl may he Hue to the exhndHtion nf the 
ntttmnt mntwal b>' the more rapidly gtxm'ing 
iprophrttt, vhereea in othora it mux be referable 
an antagoniHic action of one organism on the 
other. On tin* othc^r hand, the relationship may be 
a favorable one. The existence of anai-rcbic or- 
ganisnifl in nature, prtch ss the tetanne bacillue or 
till* hnriUiu of Tnaltgnnnt edi^ma, mm- bp favrtrnl 
bv a luxuriant ^owth of aDrobic orjraniitnd \n 
thHr immcclinte vimitv. 


tSF^Tiox Ayo ;w.wrv/TV, 


Th)B rciatJoniihi|: in inrc^tijratcd evpci'tmf'TiUlly 

t'ithpr by growing two i>rgan[fiiii« jn inived cnl- 
lurett. noting aubaciiueiitly wh<;thti- oii« hsu onX- 
^tyvru the other, or one mny he s^rovn ou a roe- 
Llium wliiHi lijw piwiiM]E«ly hi'fti itlili/nc) by Lhft 
other. The prcdonunaHce of one or ilie oUnr inny 
[Iqitrnd on tho nntuix- of tW ciilCitrp mcdtuni. TliU 
|.iriiR'i(jle i« ulili^ed m oMuiniii^ pint cultiirH^ of 
ttic cholera tibrio from dejecta by the lue of a 
strong nlkflijiie mtHHinn wliieh fftvorw tlir irr<^wUi 
nf the cholera vibrio b;it inlitblU that of tliid utiitr 
intcfitiral bacterid. Siniifflrly the flipVitlieriA bad]* 
1(19 grows well on iioonicr'i liiood serunK whrrcnv 
the other orgBniem* commonly fonml in tJit throot 

Uarrc tLintinguiA^icd a one-videtl nnd a iimtual 
actagoCLLiaQi betvecii bui^krin, but the formc^r secme 
to he tho nior« roTPnion. Exainplmi of favorable 
ftvrnbiutifi on Mjitnblr I'ltlUiri? tiu'iliiL fixv th« fol 
lowing: Strcplot'ocais ond i^holcru vil>nt>; nnthrrix 
nnd pyocyntkflus bajrilii ^TurrtV) ; diplithcna baoil- 
iuA ami lh<» iita'pli)i!iiL-iruft (ITtlln^rt). lu pljiti- cnl- 
tiire* it ba» bci-u fouuti titat tht [iiflutiua hacillua 
produces uDUeiially large cioloni?» when thev lie 
ndjAc«nt tci colonic* of l)i« »t«jihylo<*uceiM (Gr««i- 
btfj)cer). ami UiaL it ^row^ vigojouifh on a^ar 
which coDtxun:} killer] beditrb of tlic genococcim or 
Uiphtliei^a bacillus (C^iam). J1 hut been not^ 
tliat the diphtherin ]jaHIUi« Ih »ti^]inlat>vl to a 
(Ttcot^ production of toxin by the presence of 

The coexfcit«ne» of two or tnore mJcro-organluns 
ia n morbid «oniitiOD ia of frequent oeeurreiice. 
imd aom4 of the most intcro«ting and intportAnt 

vusn iyrncTtosg. 


phenomena of infectious tiiecascs arc rorcrabio to 
mixed, aeoondarj or euperimpoeed )t]fectione» 

Two exogenoiM iiifectioDK may aiimyk an indi- 
ridual at tlw »ui0c iimt. Measles aiid &i:arlct fever 
and diphtheria and KCiirlot fever have heen known 
toGoexUt, Pot*utucn:oucuH pneumoaia and typhoid 
fever^ cbnacre and soft diartere mih poa cocci, 
Hyphiliii and gi^nnrrli^ix^ fHplithiTJtL vitli eirepto* 
oood* tetanus witli goDgrcnc-producing organism*, 
are coniiQon ob«crvatione. On? orgnni^ni may tn- 
titirify Uir ^irulrnr*' nf Hnt>LlHT- DiphUiuriji iwv 
companied by etrcptococcLta infection sccma to b« 
more riruTent tban diplilheria alone. It ia alto 
brlit^vt^d thai tlir; prt'JM'iuT' nf iii^roblc □r^^nm^trnt 
(those which demand ox\i:cn for their develop- 
ment) ID a wound infected with the tetanus bacll- 
Ina or tli^ baeillna of malignant ^ema (nnAeroMe 
organi^mA), mnj increase Un? virulence of iJjcwe 
infcctionsi, Str*ptoai>a?i nre pri>l>ab]y important 
OTg&nifline in ecarlut fover, for thej ure pr^ent in 
iinii«)»il niimLvrK in Ihi! timmt leaions uud nrr 
o/leD found in fatal cawa in all tbe oryauii, vet it 
i$ po«AibI<^ that ihoy inAu^rnU only a mixed or 
wcondary iufiSL'tion *Ujn-'riinpfMiad on that a1 the 
tfcaHattna virua. The eondilioiu are Aomes^hat 
fiimihr in amollpox, the puAtulca of ^hieh invari- 
ably contain Ktreptoeocci, fttaphylococei, or both- 
Jn botli et-'arlatina and amallpoi tbeve Aeooiidarj 
ufvctiona may be rcivpoiiiiI>Ie for many fatalili«. 

I^mtmoooceiia pneumonia occurring dunng the 
C0UtM of, or dtiiiog oonvaleKOUeo from the «rup- 
tlve feTers, diplitheriii, typhoid f«v«ror tiryni jm^Iju* ; 
a strep tococciia ficpUccuiia developing d taring 
^pboid (^ivin^ ritie Co an irrogvlar temp^iBlure 


isrscnos asd iMUusnY. 

ciirsc)> Btrcptococcua infoelioD of tubw^JuUr cavj- 
ties, and xh^ developrnpnt of nculfl tnlwfciilo*Js 
during nivulo — 11i«oe an- important eiamplcs of 
■ccoDdnry iufoctioof. 

Wr shoiilH ii;iliirullv csimvi ihni iJir |ittwij™ of 
a «overe secondurj mfoclioci might oittbazraAS tt- 
tamptA ol fteitim tlierapy and vaccinal tbenpy 
Exprrlcnc^e r^gnrdtng Uic former '» limited |3Ta&- 
ticaJly to dipJith^rijit ond llioro ifi no kek of en- 
denve 10 ehow clint tlie dine^iM? wli^ti rnmplii-Rt^cl 
b.Y K'vtTt itTcplococcua iafectiou aornvtimn-a cao- 
act b(^ controlled by antitoi;lii tT«atmeiit; and Id 
TAccinsl tlwrjipv (injcition of Tiiii-TO'iir]inaI»inEi or 
their producta) it is frnplinnzed froiri nil s^idcA that 
in the preeeTice of mixed inferlion h is aHrfsuble 
to inject pre|joration* of tlw sc^ondnrv »^ wdl aa 
thp primarj' Ofj^nitni« ccnftrnsn!. 

3T AFTER Tri. 

Infection Atria^ 

The uifcctioD atrium ia tli« prJiuai} point of 
tuvftFiOQ by ottcTO^rgiinifme, or tlie point or tiasoc 
or flurfaei! UimugU w\Mx ili*?/ r^nc-h itiU-rnHl 

In general, taier^-organi&nu may enter the Uocly 
through Any of iU ^nrfiKWn, exM?pt, of course. Lht; 
•crous covcringi^ Anatomicol stnictun;, however, 
reoden thp skin, unci <?ther xiirfnrf^ whlrli nn> 
dotbed vith par^ment cpiULetium. quite reebtant 
to pecetratioa. in the absence of wounds. Leav- 
ing vound ittfiidion cut cif ccTiaidciatioii the itiu* 
roue tXiJUctf nfford tlic nT<''5| frcriiicnt pointjt af 

Certain tmcro-org&njeni^ npprar to hnvc n prc<)i- t*r*r»r*4 
tedion for pftrticuUr tiseuos, prvferring ono point ^^^^ 
of entrance or primarr inTolvoment abo\e all 
otbOT^. Thus, ia 8C far ofi we know, the typhoid 
btfilltu infl the tholcra vihrio iilway» produce 
ihtir priiDnrr infection' in the int«^ti3eft, although 
A hfrnnto^mona ^hoid ie comotimee spoken of, 
the tnie atrium escaping detection. The dlpli- 
thcria badllua habitually makctf iCa attack in the 
upper reipiraTory pana^eK It in probable* thai 
mcaalef tnd fcarlct fever ntilij^e tfje Tespiratory 
traet for th« poiat of invasion, although this can^ 
net he determined positleefy at pPHeul. Am viU 
he described later, many mirrobci hare a prcdtlec- 

li fXFKvriO.V A\D tu3tvyiT%. 

tioii fur (%i1diii imuv-i afUr tljey reacZi the interior 

of thr b(jd) . 

Som^tiiiiG^ it vonliJ jippoflr thai a pnrlicnilnr 
surface ia predilectol ojilv becauee it i» the area 
vvliich ia moet oommonly (?xpoe«l to infectioD^ 
Thu*, jf.Vfibilipi i* UftLinllv II vpin^rrnl ilUt'tM*^ bI- 
though on proper expOBurc chnuctr* oei:ur tcndilv 
on the lip, the mncouft mefiibrane* of ths mouth, 
toQ&ils or tlirough wouudA m llie akin. Hence 
li\Q pmdilcctioD of the pHinars' uotv for the gcni- 
UU ih w\{y uppnrriit- Also llw iliphUii.n"iH Imi^illus 
occoiiionally m irnjculntcd into woLitid;: on^^tjinc- 
OUB snrfaoffi nt\6 in tho vn^inn Some mucous 
surfacn are protected agaiaat inicrobic invasion 
by the ohanioler of their aeereiioii^, us in the cow* 
of i}w Htoiuadt Hnd vnglim (Sw iintler "\ntnrnJ 

Crri'iviirn- Jit the fo-calleU crypto;;eii*tic infeetioiis the 
""^ uonaT atnum evcnpt!* iltlocUon. CfsHnin micro-ot^nniprn^ 
mny enter tho bodv witlicijt cnuftirg a HisrovcrohTe 
rpnrlion nt the point of entTonre (plogiie). Ea- 
IM^nmcntdiU it !ms l>fpn shown tliut tulieicle bo- 
dlii r^fidilv pa^ through thn iiituitinni wall into 
tJie mesenteric Ijmpli glnnJs withonl miii<ing le- 
aiooa of the inte?linee. LouoocytoB may carry or- 
gflnlsniEi throDj^h the JiUa^-t i^nrfneL' of the inta«- 
tinea into the tWprr tiesnei. unO pos:<ilj|_v tlie ^arnt 
pTOCGSB oceiire in the lun|j^, ]jnrtieuifl rly \n rt'lii 
tion to thp (iibi^rrlc^ hiifitlvift { !), 
■kill. Tufcc'tioij thrcju;;h ih*t skin annmonl; titkc* 
pIftCL? thron^rh wound? [tclBmis, glnndcTs, mnlic- 
nant cdenm and puruleiit infeeJinns). although tlip 
woimd may be ao ^uioll a^ rot to be 4^ifco\enil>Ie 
(hubonic plfliiuc)- 'MiVftC<i- borne" dieeaacB nrc? 

"" moailflt^ through tlie ftkin by the biU'i of the 




iHP^t*. In thr Glkfcr of plngnc thn bjictlH may bs 
dopctfiW on tiic slcin in tbe f«cc« ctf tho ll«a nn<4 
aubn^ijueQlly inooiiJAted Ijy inenitN of nibbing or 
KTilching. 'Hjc ^uinea-pij; may bu lufi-ctci^ with 
pbgiu by rtitibwg n culture ott tlt^ ahuvea ^kin. 
Hinnte wounds probably exist. ^I^phylocgcci may 
n>Acb the liair folltclee tic a coneoqucticG of rub* 
bing and came fumncnloeifl nfUr jjetiet rating Ui» 
soft cp:th<tlium of tbc follicle, 

Tbc oonjuBciiva ha^ ratJicr hij!}i reHJ^taaca for 
?umc micru-urguEiihriLiL, ua tint Anlinux buutiluH, 
and It lurb<)r» vtnphylococci coctinnouflly. It may 
bft invnrl^, however, by the gororoocii* (pijwdnlly 
is cbiJdrtiik, pncumococcuA, »UeptocccciL», fitaphy- 
lococcua, di^hiht^na bat^illufi^ MuraA-A^<>QfeId bn- 
rilliu^ ami pnilmbty Llrt* tnitiiin^tKOCiUK. Thi? 
pU^uc bacillus trill ghuk jifcncrnh^cd infection 
thiAiigh lb« <M-mjnncti*ft in rfttn, and ii U rei«irtod 
tJidt gUiidtiB and hydropbobia (Coat^. Galtierk 
may alto gniu t^iitranov tbrouj^h Uiu coujurictiva. 

The naial pai^agc-^ lttff?i>iiif Lnft^ctod ivJIb the 
organbnia caiuiiig ror)i:iL, willi the organiatn^ uf 
dipbtlKrln, influenxn. iclundon, kpro«y and with 
the pjo^'iTiir itn-c\. Sciijie of lbe«e mny evternJ ti* 
the adiAC<.-iit taritiea* aotTuni of Hi^'hnioro. fronlril 
dntiMa, aud the middlo car tlirougb 1lip I^uatachian 
tvbiL On account of the proxiaiity of Llie tmval 
pa w a g w to tbo brain, and the lyniplialic oommuni- 
ntiono, it >fl probable lliat mi^niii>(itin ^pnei:mo- 
focctc and opiclcmic ccrcbro^pirtnl) often arises by 
»t«iui<»n of the organi«nie from tlie no^e lo the 
mi^mu^ thmngb Oi<' t'hhrnoiil, 

Actinoalyco<Ii^ nvpbilin, occnuionnlly tubtix.uliF- nooib. 
lia (tongue), noniu* thnieh, and in children gon- 
nnhea may flml priTriar%' IwHtirin In the mouth. 



nrrscriox a\o istuasm: 




Streptococoi, I'&cumococci and diphUima read- 
ily Attack the \atm\Hj And il ie jirobnliJe that th« 
tubercle btfciZliu often eitte» Uirou^-Ii litem, vritli 
Of vrlHiont causing local infection. Simllarlr it it 
ldiev»*d l]) iimny Miat urganlamft causing HrpUrf* 
tftia (partieulfiHT llif! itrcptocoemje), ficiJtc articu- 
lar rhi^iimntittm, itnd rk£t«oiny«]itie n^ay e&t«r 
through the tonsils, and this may also be ihe raw 
in «car1«t ftTer. 

Tin? bronchi bwomc infw^ed by the Tariouii or- 
gauiBrnfi CHusLU): bronchitis (etreptocot'cus, pneu* 
mococt!Uii, tnflunnm bnrillus, «te.), and, citbc^r 
thmu^h juirfncc or lynipTintiV ext^nnionj or by deep 
infTpiratioDf theao and many other or;;'aniamft, fu 
tbc tubercle and plagLio bflciltt. and th^ actlno* 
fnvc«, rttch the dp^pcr rcce«»p»H Sothc of the «j* 
iiiith«RiAta, n« m^'Aftlt^ and RmAltpox. may find cn- 
trnnce tlimitgb tlic jiuTmorHTV tliitsiii?. Af^ explained 
later, "du*t infection'^ nnd *MropIct inf<*(!tion" arc 
fit gTP^i imparianvi* in piiTrnfinnry involvement, 
peidculariy in relation lo tiibcrailosiii. "Pri* 
mary" tuberculoeia of the peribronchial lymph 
gTftnda indii-atn tbiti. wojue rnicroHirg&ni^Tta may 
ttuverw the bronchi iiilhout involving them. 

The •tomoch i* wmporatively fre** from infcc' 
tinnii, TTie Intwliripn provide nu iitrimn for ty- 
pboSd, cliolera, dyHent«ry (bAi^tllary nnd amebic), 
tubcmlotU, pUfpii^. anthraic, in chiMr«»n for the 
atreptococcus liaciUm' pyoiyfinein and otiiers; in 
animaU, for onthrn>-, piflinit-, ^witio pln^c, moiiw 
typlmtr pbldtfn cliuUra, hemorrbtgic Bcpticemias. 
mtcftina] diphtlicria of rabbits, and others. 

The extent lo which mtcro-or^Bninns arc earned 
from the inttftines into tL« bo^y in a stat@ of 
bi«1th is grentfy difEputed, but frequent oiSstence 


iTirEcrnnr uf EXcirKTiostt, 


of pnm&rv tuberculosis of the raeeenteric Ivtupli 
glands tndicaU^ that it prc^aUy occurs. 

fUettjtn, — Gonoirhen, seplic iototioQ of hemor- 

t'rrMpfl,— OoEcrrhca, syphihe ; "eimpic"' arc- 
ifaritU (Sue to ether caus% 

Bidder and UrtUn. — Tnfc<Ttjon usijallj swoni!- 
m. bj exfcDsicm or from the blood dtroam. 

Bstfmal G^iidis.SkTd and eoU ohanare^ 
Di]iljUicna in girls. 

FtmaU Genital I'fccf,— Conorrhea, specially in 
Ibft cerm, vhich it co\-ered by ^of t euboidnt epithe- 
lium. The r^gma i& <{uite r^i^tnrtt owing tn itfi 
coTering of pavomeot epithelium ajid tbo hactcri- 
oidal ^&ract«r of its s«or«tion. Virulent pyogenic 
or^anSsma sf^mctimee are found in the nomtd 
TAginA und they mAv ociTneioziiilly be rs^poriEtble 
for puerperal infe^'licn^. 

The above rcfciv to primary iDvueion. It id well 
knovD that many of ihetf. eiMtaccu and the orgnne 
vhich they cowi are frequently involved subse- 
qiAODt to ini^a] infection at gonia other point. Tbia 
!» •iM'ondury^ or, bt^lttT. meta^tdlic Infection. 

EtcrrtioTt of MtcrO'Orffanutns. 
Td the tranflmie^loTi of an infef^tion froin person 
to person, vrithout ttic intervention of un inter- 
nadtaU ho«t (iDPoctK), tho pTOC0it« nnturnlly pra- 
snppoM that th>? micro-organ iems are excreted or 
diMhargcd from the body of Uie pnftcrit througb 
one cbnnne] ^r another. Regarding the likelihood 
(if Imnfitniuiini^ ti» thp rvi^nt tit rtrrpHon, tJiw 
vfiW dqitiitd on the diftiacter of the orifaniam, Ita 
riab:iity undai th« eonditioDe of excretion, the in- 
fection atrium vbSch U drmnnda, and whether or 


tsrscrsoK j,vo lUMvsnT. 

Ilvlntlnn nf 
111 iri>l i'*iH V 114 . 

not it u diwhar^ in ncvh manner tTi«t it ]« md< 
ily diawnii Tinted. Sonic of Uj*** pf>int« aw con- 

A* n general jirinciple It may be ttnted that 
when the SKrfiicee of the bo^y air lli<r Beat of infffc- 
tion thi» miero-orjrnnifms nre <li«ohnrjred into t'l^ 
oiitrr world more nr lew pji^ily Tliiji n[hplii**: not 
onlv to th'? futaaoous enrfnoe* li"t aleo to Uio ran- 

)>lB(1ilcr, flinl iirinnn' bladder, nn*l also to discbarg- 
in^ idnnKog pnd ]ih^p$»;(<s which niptura through n 
ciltatK^ouK or inncons aiirfjir*'. The niirfarps inaj 
bo iiiFolvod cithor prin^anlj'. n* in twhcrculoeis or 
hla^foimeosiK at the Akin, or an u part of a freif^r- 
alij^'d infection, ns in thr ohmt of jcmr of Uic 
uniptivfl dUwtcp. Thus from the rc^iratory pa^ 
ta^cA the luioTohea of pn«uuionia, luberculoAia. 
diphtheria. totiBillitia t'liuiort by other micro-orRin- 
ismn, pJagiic iin^^nmonia. inllu^rivjiH whooping- 
cougli. epideiiH*r ccrchrofipiDai mcoin^tis and 
probably i]ieaeli>e, ^flrlet fever and eniatlpox, are 
diRrhurpvl into ihi* unrrounding air. From the 
int^'-fltinaJ (met the njirro-orgnnisme cf tabrrcu- 
losia. typhoid favDr. cholera and nf other lea* im> 
portatil [liirjiic* riTflcl Hit oulcr worJ^l. From the 
^mtovnnory tract. Uiortc of gonorrhea, syphilid 
tuhi<n-ritoHU^ typhoid Jiml pHrafyplinid fevers: fn"n 
the pkin the microbee of ulcerative pToce^as, the 
t'oniapo;)* (1ermntofi>£» tmhciphytoiii!, favus, etc. 
and probablv aonie of tlte oontA^ioiia eianthemata 
(warlcf fever, mtaalta, ete.). 

Of jfTcat impoitance is the fact that some infeo- 
Hnnu which nre primarily lyateiuic. or heoome so 
diii'ijig the course of infectiOD. r-ommonly iiivcilvr 
fcom* tierctin;; organ tKcondarily, Ihna renderiug 



laio». In a Ur^ pertrntage of \ht cni^^9 of tvplioid 
JeTcr llw kldii«v« b^jpfmi^j tbo w«t of nuititrous 
fcri of rni^silntic* iiifis-ijon, nriLiUiiig in tlic rlim- 
uintion of lflrp« qiiattitici of VivjnQ, viniknt ty 
phoid hacitii in the *]rine. A simifsr event l»nppena 
in i^amtjpboi^ frwr, srid m ^v^1cmjc titbercalusia, 
knd Koch hju cr^n *itj^pHrtod tKit eLecpiOq eickneei 
MJHV l*r iirqiiinn^ liy cfritiii. "Milk sicktip^s,'* w!iicli 
«pptf?Atly is acquired tlitough tlie ^afttro-intcj?- 
tlnfll tract, ig traiuniitti^ through the milk {Jot- 
(Uii uiid HarriHl. and ilic t^nuK: i* Irui^ ot ItfalU 
f<?t«- The vini*! of hylropbobm i* n5:crft(iMl 
through the pnlivary glaiulK Riperiitientnlly, 
pMWnoOocci oiiA anthrax bacilli, vhcn injoded 
inlo th» drctilatlon, have been rL'oov<>red from ihe 
intestinal tract, TfiiEt -na* also done ^ith tlir 
vilrno of choirm in gtiiniFA-pii^ f Kollc< and 

Thcpc sintcncTjls btc made with reference to 
tlic diAohar^ of micrfl-frrgnTi lhih^ during actual 
diMeae. InveAtigatious liave ^h^un, hoivevtr. that 
Inflections on a Jncije *calc. reaching even c[>iik-mic 
p*o]i<miont, lire fn'<jucntly denvrd frnin those who 
npporently arc in n rtnte of gooil health. Usually. 
but not fllwayp, thie **onetfma indiridnalB who have 
fliilTf-t-ed frofii \hK Infection at »oixie previous time, 
and thov arc kiioii'n oa "bacilliiK camera." or sim- 
pli ■■tniTier*-" 

Tlie ribrio of ctiolera mav he excn-tcd in the 
ticub for forty-cijfht days after the rceo\erv of 
the paUent (Kolle) Vinilent diphtheria bacilli 
mar br diichorged from the mouth and nose for 
tnontbg fiflcr rccov^y from the disease, and ui the 
caat of rkiniiit fibrinottt chronica this may per«ii;t 


txrMCTiox AXD iyMt:\m\ 

for yt^n. "L«teDt" ^oorrhca u frc^tt^U^r in- 
f«GtlT«, Tbe uriAe after re^OTer^ from typbold 
fetifr ma^ oinUic the bacilli for mootlu (Fr- 
tnucbky and others), and tfaa nc«ot ctodr of ^• 
piMid carriers hafi i^ovd that tlv; may diachstge 
bodlU ift the stools for inaor yean (twenfy or 
moire). In some iiMtaadM it bas bem uppoaed 
titat the gmll-bladder ta in a stat^ of chronic in- 
f«ctioD with Uie bncilli And mttt^ a« a ratorroir 
for continDooa Hooding of th« inteetuwa. Tlie 
taJne of the rocedial mcaMirt enggeatcd — L e,^ Uie 
extirpation of tic i^lI-bUdd^r — ha^ not yet faaan 
damoQttrate^l- Wt; cannot leave out of mind the 
poaubalitj that the tjpboid b«rtlitt£» in ^oimc io- 
ttancvi^ may b«<^R>e Tiabituat«d to llw intaatina] 
corironmeat and multiply there; b soch caaca U 
would not be Mceuary to aauroe another wurev 
of replcaiihinent. The di^tfcmination of ntii^-ro- 
OTganuniA bj inMicte whicb hav« fed on iDf««1ed 
blood a apart from e&cretiorf end is comklnrad 
under tlie ntibj<ct of '*]nj)»t Tmne miff ion" Cho]H 
tar VL}- 







(/) Earik, Etc; [S) Pood SuManctt; ($) Ani- 
inais; [J,) Bcdy Surfatts of iht Individual. 

Uicro-or£Ani£m£ vhio}i produce diMCUsc in inan 
mAjr l>e d^rivpr! (T) friim lhf» mirlnh, ntKrr Inniii- 
nui(« mAUml. or from ve^toblc ^owth; (S) 
from crater* milk or otlior food dubitsncee; (3) 
frcini iiijim«Ur din^lj ur iadirrT^Llj; (4) from tlit 
body sTjrfaco^ of ih& indiruJon] himnalf ; <5] from 
other fcnman Ueing^ anti (fi) from hisw'te, 

I, The wlent to whkh ibe auperfJcial uortli is 
conUmmtU'd wilh micro- or^'auUuie depends on 
TihoUtt cotidilioitji. jintlinilurly Uir prt.'sencc of 
doftd organic ntRtt«r, moipturt^. toirf}cr«turc, the 
dfigTve o( exposure to f Jglit end tnriliglit, the chem- 
ical compcHution of iht »o\\. and the admixture of 
tnima] tixcroUoucH Somo of Ihcm tnhubif the noil 
DAtumlJ^ anf] htv roiTipiirotivi>W hnnnlfM rapro- 
pbv1«e, and muy cwn i>a of great value in the 
rt^cmrratjon of aoiU. Others^ of pafhogflnic char- 
■ctcT, accjn to occur mittirally m the earth or gd 
T«g«ttt]OSi, vrhQr9 th<iy multiply Tonciily (th*' pyo- 
genic 00(^1, actiTiomvce*). On th-? otlier hand, a 
Urgt number of pathoi^Dic orgaDiama reach tDan- 
imniMt Daturv only an tJicy are deposited vtlih the 
excretioD* of man (tho«e of typhoid, parntypiioid, 
dyMDt^ry, cholera, pla^i», tnhprmlosiR, e('',),or of 
anJoR&la (t^tanuf bacilli). Itlanv, an the- ur^inl^tiia 
of trphoid. cholera and p]af:iJC. probably do not 
proliffTfttf* ■( all in the rnrtb. althALigh ^omp (let- 



tyf'scnos j,vi) iiatL^nr. 

antu bacilJiifl Kind thnt of maliguunt odomft) re- 
tain life anil virulence inr a Inn^ time. It is «till 
imcejtain vhother the latter proiifcratL; m Ihia ait- 

ualjon, or whether tlit-y |wisifet merely through Die 
agency of t^cir rcsistnnt fpore^. InAeTEnich hb thn- 
ftr9 oii&ercbic in (^hnrjirter, thi^ir ]lf« iimv in eotue 
iijfllflDoea b& fti'olciiig^il tlirmt^li Etyinbioitc Ai/robie 
organbm?, wliidi sqrroimil llxem &ud croate far 
ihem iin utniosphere which is pour in o\jgim. The 
I'Tcscncc of nino.v nBpropIiytes is niifjnrorfthlc to 
the life of certciii raicro-organifins in the soil (ly- 
[jliuitl, [ilii^'itv)- In vo far as h kuoivu none of 
th(! (jrotc^^CQ whit^h arc pnthogimic for tiiaa occur 
in thiT ini] nulurfllly. 

'i. WwUir, milk luul tiihvv tnctl subslmn^i?^ inn-ly 
hnrbor ttnpurtnnt pnlhogcjiic orgeni^ms undc^r nnt^ 
iirnl ronditioM. On the other bond, they play n 
very important part in carryiag *uch mici-ohea 
from man to man, and iu eoru^ In^taiKei from 
nrimiiiU En wait, n& eApTuiiitO fii hULmeiliii^ rhnp- 
tere. Stagnant witter frcqyrntiv seta up acntL* entfr- 
ifia, ivhlch may in some instances be iTvio lo ita 
chcmii^iil conjititiirrrtH ntici in others to gnprophytic 

Solitl fondii- ua frniU nnd vo^tnljle-i, may ooc-n- 
rioaally hoihoi' bnclcno, particularly when in c 
8tat« of decAV, which liav« moilerfltc pathogenic 
jfowev* for the intealiiial tract; or, ly providinj? 
suitable aliintutalion or otliem-isir modifying tho 
ccmtcnts (ir reniHtaiKc i>f the Hlinieutrti-v trnct. may 
render organiftiii* virulent whidi otlicrvriee wmiM 
be harmlcic- , 

Meats, healthy En the ffi-st in«tQn<*ef are ^ibj«ct 
to invasions by micro-or^ant8in<4 frnm tfie inles- 
tind tract, after t1j« death of Un? artimrtlv (fowU, 


rxrtccTios rftou }iiLK. 


Ml. oj'ettff), or thcv mav be c^aninminatcd by 
uncleoii and Improper pt:e«ervatioE later, yha 
irmptoiTtf cauMfd b/ tli^rir itigcetiOEi ai« actual Ui" 
fcctiotiR in Komo mitniiccK (ad ^'itb itticiUttg tnla-- 
Uifiis). whereas in othprv Hip rnriilitfnti mnv be on? 
of itttoxjcotion Iv ihc ^rwincU of wpropbytic bc- 
livity (Bccitlvs botulinics). 

So&jo T^geUbles ooctflin Tiighlv poioonoiia nlki* 
loit^n Btii) toiiiiH^ whirh rnrMv rimS n p}ncv in dla- 
eaAe. Some of them have been of f-rcat taIuc in 
tbe «3fp«n'ni4ntal fttndy of toxine and tintitoxic*. 
(Sc« labl* nt L'bi*e of ClmfU*r I.) 

3. Animali art somi^limi;* subject lo infK-tion Antvnat*, 
by microbea which aro also jiatVoirenic for man, 
triQimiAvion ivX\u^ place through the eonftnmp* 
tkoa of discia^ed medt or milk, or through direct 
or iodircct contact^ tiirough vounde^ or b_v Uiu 
hitcf of inaecU. 

In bovine luberculoffls (he udder h frw|HontK mnu, 
mrolrtdf nnd in luch case* large quantities of the 
bacilli aro excreted by tbe milk. Altbouf-h che 
virnlpnnp a1 thp hnvinn huHlhi* fnr uifMi ninv nirt 
bfr io gTat as that of Iiuiiian tubrruuloai.i. it ia 
IMV troll cfrtablished tbnt it ofttn infecU man, 
p«rltn)» L'hitdrffn more* friMji](fiitIy ihitn adulln. The 
t'uw's viddi;r If ot'iaflituially involved in iiif<?ctiona 
mti) fitrcptococci* vbich. being cxcroUd in tbo 
niikj art cajmblc of causing severe onterilie when 
lilt* milk ia injje^t^l. 

Tbe mvcroK^r^aQlBm of irtilk aickoew U tran> 
f^rrvd ID a «iiriUr wav, and ooly recently it has 
tieen ahovn H«ar]y (but nisn fin Malta ^ U-ourn^fl 
infected wtlh Malta feier tiy the ccnauiiiptioii uf 
the milk of £oAtK A very Urp? peTomUi|:c of thwe 



Wr OfrviA^i- 

Dr iB»*v«ii. 

flninifils Wria found huffei-hig trom (lie dint^aiai!, nnA, 
aoce Hit nee of i^oat^e milk has been proh^it«d, 
thg fncMfxicc of thQ diRenno tn mnn hat iindorgonp 
na AttonishiDg dccT«ft£e. It Fcenift to h&ve been 
dVKioaetTAtod thot lotli Liorsce and cattle oivn 
t&OiMy »u/Tt?r from ^luiJ^niliKiril EiifrirtJons with thp 
purah'phoid bncilluis and ^ith Hacillus mti-riiuHf. 
And epid^riiic mfedioDft wiiix th« fcrmcr huvc bocn 
trncird to tlir- roni^Timption of diwnaed iii^aU. Bot- 
ulism and tnchimaala are dmrc^d in tlif t^aiicf- 
vfay. In voma iotrUnon infection o( the meat 
prnljHhIy luki'f* plrtcc (Inrin^ic or 4Hb*0fj;ient to 

AntliTUj:, gUndtTf und iictiiioinyco«i» are ton- 
veyod Co tnia from anJiaaU bv contaot, tbc ftrst 
two li(*n]g<'ciiitiij|Fi(iux; iiniT bydmphoMH hy tli^ bitM 
of rabid flDimtiltt^i. t., hy wound infection. 

la A few instnncc« infccfionK arc transruittcd 
from ao animal to >uan b\ means of inset^t*. Tliua. 
the conveyance nf pTngiip fn>ni t,hp rnf, by the flefl 
is ono of tilt meant by y/liKh man rontracbi tbis 
diseiwe, TJw U<?tfio fly of Soutb Africa, which 
inociilalofi tnan witb the Erypfincwome of tileeping 
nio-kncw, Mxmp to dcri»c its iiifvtrlioa from wild 
animals Id eome infitnnrc«, olthmj^h hnmfin pa- 
ti«ntc ore oUo an important source of infoclion for 
freab f1i«^^ TIil- viraa of lEockr Moimtaiii epolted 
fever probably pafF«fi at Ica^ u part of its exist- 
onct- in the body of one or more ep^cii^e of amall 
wild animaK and this step awms iii>c*'>i9H ry 
for the mainteuance of virulence. In connection 
V'ilb mAlurio, rulnpfing fcY*>f, Smith African tick 
fever and the piroplflsmoses n third host sptrm.* to 
pfijr no rtle, or, at any rate, not a neceesary rMe, 



Snake vononip. arid the poiFonii of ttpiijcro, bMe* 
iod mrioQd iaBectv, are Ioxidb of nntmni origm 
tfhEdi 1i£vc pathologic &n^ jLcieEitinc importance. 

4. "Eodogcnoiie*' infection or "ocloiufcctioa/' 
By thia term wu mean infection of sn ioiivid^ml 
by Riic^n^ur^uniHri-i uhtuli rtabtJc uaturallj on 
*omt mrfftcc of the bod/. Such orF^imna pro- 
duoe infection nnl_v whor lomo other fiu-lor, |>nT- 
dcularly trauiiiatj«iti> come8 into opcratkn. 

Hair foiliciw frctiucntl;y contain staphylococci 
anci vhen occliiHlon otnirR the nr^tanUm^ may pn> 
dttoe a pustule or a furuncle. An icjur;^ of the 
coQJu&otWa may rtflult in infection bv »i8phy- 
lococci or pnnitfiDrtKx;!^ vhicK arr present iionnalN, 
and many wound infoctionn urc due t^^ orgnnismB 
vhlcli pre'fiist on the ^urfsce. 

Probably a facicr of great import^Qcc for the' 
inTBeioii of euch orgnniems ift a coadition of low- 
ers) re^tHfance on the part of tlie tissues We 
kn<t%\ for example, that virulent itlrcptococci and 
pucumocoeci arc irccjuently found in tho pharynx 
mn^ on the tovuiU in apparent health. ExpomiQ 
to cold in ^omc itiKtiin?«>e mar he the means of 
lowering th*? re^rRtance of IIk- srirfai-e^ (inliibiliou 
of tiic antibatrti^rial forcce) do that the or^ni^ms 
^H becomo more nuni«TOu« and p«n4trate the siir- 
^H face. ObaenatioD^ erggeat alio that tlte prcfieccif 
^^ of a serous oxjclate, ^wh as ei;i«t£ oven in a tran- 
^^ ticnt iafliimmiilion, umy raus4* um mrreaae in the 
^ft rimltncc of the or^animne which arc bathed by it. 
^M Similar forcn may play a role in tlic bronehitie 
^M and pnemnonis vhi^^h fnTlow expo«iTre- 
^H Inhere »ceji;> to be comparatively little dinger of 

^B "autoinfcction'' from pnthojrenic bacteria which 
^H «iwt ncrmally in the Jnteftina] tracts etcppt in 



jxp^Twy AXD tMtyuyi'n'. 

iHe cHvt of tnnmHtiHiiiT n* in iiicnrc-omtnl hvmid. 
or in KTCK ronfftipatinn, c»r vhen the normnl 
redftinct* oi the inU-^tiii«?H hue been imioti rtw- 

iurb«d by iiii|jiupi-]- f<ioil. 

retumli-MyMrr or n^infn-Linii liy urpirnKinn which 
liavc pcmUtcd at Krnic point followinje c pi-ctiouf 
nttni^'l^. It^lnpAM of t^^shoid ttner an^ recHrp^nwft 
of fflcial trr^ipela^, and frequ^ntU Utt^ flaiiii;; up 
ofatiold (IfttL'nt) ^norrlioii, lUualrato tlii*. Mate 
milinrv lubi!rruic»i^ or LuEirn^uUm?! Titciiin^ittBV 
may follow the escape of bacilfi into the cin^nUtion 
froii] an nnsiispKterl focnsi ir» a perihroochia) 
l>mpli ^fiiid. Till- mauif«tl> i*i uot ftutoiaf»!- 
lion or ondoiTCiiouH riikv-tion, smft'. cvi^n in tht 
[>1i] liiti'til. fiH^i, Um* infcc-fJiTn d^iLr-^ l»Ji(^k ta n pi'ior 



(S) Frot'i Man to 3t^n, 
Aft iikdicatcd in Cliipicr J. th^re aie all <leii«e« 
ill the fodlK} witli which infcclicmA diseases m*e 
trimmitted fioiu one person to another virymg 
Cirtiu that in vhich it ;i o[il_v noceemry to bro^Uic 
thv air HurroumliiJ^' n jiatii^rLl (?^:iii]et fever, 
mcailca, influcnxa. tU.), to chnt iu vlxich trouS' 
Diift^ioEi iiftr«r takp' placp under orOii^nry circuni' 
ttaiK>^ (tetanuf, ]>}iJrcpLobia), 

lb home JnstAnce- a bj_'lc-al ivlotioDehip eiUtP K«i*iti» 
betw««n the facility of tninfcirLieston. on the one iV/c'u^i 
batiil, »nd tliv fonn of c-vn.'tion t»f tiw mirru-or- •'*'''^**''' 
ganiemfl and Uieir preferred! inf«c1ioo atrium, od 
the cthvr. Thuf in inany di&eoedft in which tho 
mii-m-vr^nunift nrr r^rrrtefl from thu nwpinitary 
psaeafett the latter are aUo used as tlie infectioD 
ntriam fiofltiODai, Enco4lc«, iTnallpox, ctcO^ !■> 
oHitXw, ill which ihev are ^\L-reted mainly by thu 
iDteaiin^it. the iofrctiofi ainnm w the iDtc«tinp# 
(trphoid, ohokra, dyacDtcry). E\x^ if it wcTt< 
poaaiblft for the organisiriB ot typhoid and ctmlcra 
[o gain entrniiri' tiiroii^h tW luiigv (mid itidt^d it 
niPT be fxif'ititr in typhoid al leo^t), th«: fact cf 
their oxcrelion mainly bt ih* nlnoW, and by tht 
iirinv in tTphuii). muild ronder piiiiiary pulmoaari 
in\XJlTemeat difTicult. Thoy n^ncb the intertinc* 
mont rttdily throu^ contaminated food. water> 


f-li*,, L!uii lliej ecjuld rr^jit^li iha litugH Uirungh tD- 
fcctcd duft or droptcrU. Similarly, if Die virus of-, 
fteflrl«t fdv^r, vhich ir f^xcret^ fntm tho Umgt sod* 
flkin, could cati»G infection only through coUiieoufl, 
wounde^ ratli«r than throiij^h the air passages, there 
IK reniun tii Fh'Iutvi- il wuulil iicii lidJ iU prw- 
cnt ppHitton an a vcn' contngiotj^ ditu'dsc. Amoii2;j 
thp rommiiniaible (iitcni^os vri> linvi> l<i rvcagnh 
that cecli Iiu its own mechanism for habitual 
U&DRmimon^ a]tbon;;li the habitual mGchfinieaD 
iMrtv Ijp (leparUfcl fniin mi ninny opcaeioiifl, 
AirtiiniD- at A? vfouIJ Ic suppcwd. thc Ui^itaae^ vhjch ore 
moat readily uccjuirod, tlic mcEt contagious, and 
the most prpvnlcnl are those in which the micro- 
OTgaiiisms arc excreted into the air from th« r«e- 
pirntory fOJ^sage?, and in which also (be respira- 
tory puBsa^'es arc the preferred infection atnum. 
The mediuTu of conveyance — i-e., the air — ia used 
alikg by all iodividualr. Some othor di^aees, much 
le«fl contajrious than thoe^ mentioned, mfty pre- 
vail In estensivy epidomit' form, often exceeding 
scjirlet fever, tneo^Ie^, rlo„ tu the percentage of 
incidence, as in llie cafles of cholera and typhoid 
fever. This i^ commonly ^ue to an infected water 
supply, and the diatrihutiou of the dtfiensc cor- 
roaponds in largo decree to Uiat of the contami- 
nated water, Tn other words, the epidemic is co- 
extensive with the "fio of the conveying inodtnm. 

Similarly^ the prevjilcnee of gonon-hea and flyph- 
ilitt depends on the extent of promipcuous sesunl 
intorconwie; flod, of malnrin and yellow fever, on 
tho Dnnbcr of individuals who beoome hUten by 
the infected Anopheles or Stegomyia ntosqultoee. 

Thus the centra] fnrtoT tu the citmmtmicatioa 
of iDfcetioti is miitabl^ contact with the agenc)' 



4lr ■■ 

of coitwyniK'L-, atld ulivrc ?il<.1i uouLau'L cua Eh.- w- 

aliicd wiUi difKculty commniiiciilion from pcrKcn 
(o f«r«Dn nnXy occurs (e- g UlanuA nnd hydropho- 
bU, ia nhicli woiiod mocitlfttiou ia tet^uii^). 

It i« prohabic that Ihc flir, in tho ftbsfnrc 
of tttnoflphpric current*, woTiTd s<xm betome ^ter- 
Ue^ by mlue of the dT«i cf gravHy in carrYJiiir 
Uw mierobcfl to the earth, and the gem^icidal oc- 
tion of sunlight jiml illfTiiw ]i>;ht, Of couff^. ihes^ 
conditionft do not prcvm], or Arc not -^iTcctirc, and 
the »ir stajidi as one of the important s^enries by 
wliicb virulent micro-oigaaiAua r«ttch Uie iudivid- 
uftl, either from ot)i«r indiriduaU and atiimnlf or 
fium inunimiitc nature. 

For a long time it was ;ttppo<Kd ttiat coDvey- 
onco through th« sir tnkcfi pliici^ ctiioSy or eiLtirely 
ihiOQ^ the medioiQ of f iie particles of du$t irbich 
«rc lodcQ uvith micro-cr^ani&tna (**dugt inf>?ction"). 
It VA4 finly thrun^^h fiiiidHirienlat w\tk by Flu^r^ 
(181+7) ami otbcrK that it wua *hovii hov minute 
droplol* of «mJivii or muctin from tlio Um^is or nasal 
pasM^ m fully u loportatt as du£t, and per- 
hapi mor^ impcirtdnt, for th« traiufer of infootJon 
from one indiTtdaul to aimllit^r TIiIn it ''dropk>t 

Tho fielda occupied by dujt infcetioD and drop JfJJI,*'ii»* 
let infci'tion do not <^i[riridr tmrtlv- Only thoAP 
dU«a«cfl can be ranccTncd in droplet infection in 
vhich JDfccled droplets nre dt»rharg^ froiu the 
body — i»e,, cliiefiy from (he uppvr ixapiiutory pr»- 
>a^Ct«. Sirco tbe infDctiu droplets of ealiva. 
senun, mnoui nnd pus may hteomt d^jiocat^d and 
pulveriied, the field of duit iufectiou, tl leii re tJ tally. 
inchidct aot only those dioeases, but alfo many 
olhen. ThtiB, du^t infecled with the pyogenic or- 


iyt'ti^Tto^' AXD iMyvytTT, 

^immr. or vith tcluniiA bacilli, miy be dcitvcd 

fr«m oMtnarv rnrHi dr pnrth contnminatwi wilh 
Ihc drici) rTrcrtliOD^ of nmEualfl. And in otber 
CHfi«a tlri^cl and piilTtfrizrd vinoc or foc«« (typ^^'^- 
(liolcrm). tir i3fj"iiTii(r<l iliv-liiir^v fiom fliw^njiHi 
Burfaccf, fiom mum nnd abfcce^cs {lubcrculo&is. 
cnnipplftjs). may givf tUp to inf*^tGci dust. Thp 
tk'm inav he An import&nt eouree of iufecW duM 
ID IhQ de»fjtiAmatlve dUeas&s (aoarkt fevor, in«ade£. 
!<i!irtll|n)\). in tlittt iiidiviiliial lioniv (vll-i dr srf>i'!>* 
of i\^]U kdcn wiUi orjjjuniJms may Hont in tin* 
nir v>'ftb nu gr^t v(?fwity in th4 mny»ni«iiii of the 

Tho importAnco of rluxt infoc^tion iig curtniled. 
how^'pr, Itprnnftp of (he aligTit rwiKtnnrP wlijfli 
ina&r microbes ahow Agdiofit deaiecatioEi and tbt 
gtrmlciiilnl action o1 light. GoIaf^Uidj clasiifif* 
miCTo-ttrgnnismt rcgjirdiug the likrlihood iif thrir 
farticipatinp in HiiFf nfoction aa foilowa: 

(n) OrBimii^iiia whirli uri* not f^npnblu of livirip 
in doflt a^ it is dried in rbe air^ nnd hence ncror 
{ft^ely mij^ht be b«ttcr} can b« dis4eininat«^ 
Ibruujfh ilrLed particles (diole-ra, j^Iague^ goiiur* 

(b) Ur^niiniB whiob tiro cflpnlilc of bdiig par- 
riiT^ Hf cltmt for tonPhlernbli^ i]i»isiTifi^K by Kucb 
weak ciirrtnte of sir na ordinnrily Mist in dwoM- 
iiig<, nnd whirb, wh^n onr^* ensfendo^ in the air. 
rtiuiain alive for a Jong time, and v.n\\\y lead It 
da«t infection {pnn cocvi, pjoovnncnifl. nicninfl^irof-- 
eiiB. ambrnx spore^ tiibert?]^ bacilli and lelanut^ 

(c) OrKaniams which, indoi^d. ai-o rwi«lnnt In 
deeicealion, but nbir-h arv HiKneminnted lU fliiRt 
diiW tlirniigb #fran^r air currenlfi. aucb aa occur 

DVi^T tyFECTtoy. 


ivl<i^iKoiull_v in (IwictltngK (tjphoid and li 

TItU Imvc* out f^f «oitfU«nt1cai the imtnovn 
nrgnnM^K tif IW rxnnthtintttii, referred la abovt- 
Th* coodilioiiB n? they ordinnnly cxwt in dvcll- 
(nga arc laken as a stan^nnl. find tfip upighl imd 
•ise of the jwrticli*, and tlit- velocity of the sir 
in an upward direction, tn well as the vJabiTity of 
t\w dilTrmit orgAnUm^ in n dritsl i-nnditbrii an? 
the oe^Qtictl ftx-lor* which govern the likelihood 
of dust infortior. "Naturally, cmU- tlioee infected 
|ttiijcle» of dried duat wliich mty lie carried up- 
vird for a ooiuidt^rable diitauoo bv a very low 
vploi'ity of tlir ftir nrr iiMr to mnjiiti wjKfpiinlnl 
for some lime in i^t ntiuoJ^ihcre of ft rooni anc!, 
coitee<]ii«-iiily, eust ae r protracted danger of air 
iofeclioB, M. NeisHcr cc^iiaidera as tlie limit that 
tlogne of " Vera Uuhbrttk til"* m whioh lhc» ii^- 
f«cted purticlcis rmy l>c rjirncd lo it liPijihi. i^r 80 
cm, by nD air velocity inpwnrdt of 1 cm. (per 
wcond)/' (Qiiot4>d rn>m GoUchlidi in Kollo & 
Wttaerniaiiii^A Haodbndi der Pathoitrnen Mikn)- 
orgubRu, Vol. 1, p. 163), Afti^r the duv-t in a 
room i» nncc thcroniildy ntii'tixl np, from oiip to 
oi^t bonre are roquirod for it to »<*tt1c complttdy 
mdei* the nio«t favorable coDdltioiis {^tem, 
Flvgce, cited by Ootvchlich). Durit infection may 
pl«y Ik f^art in public building nnd convoynnccf 
where the ciirront« rf sir nrv rtrongcr than lliw 
(iTdiEuiiily arc ic dwclliDj*?, Even in dwdliu^. 
hovorer. tlio condlciunit are by no mcnn* uniform. 
More riot<ait cnrrc^i^U arc c:idtcd by a breese 
tbrotTgh iin op^n aindow, by tb« moven^ont; of 
|)ereoi**i, and the elijiM'^yi of infwiion s:*- iru.Tva'twl 

111 i»«i 


I'll III K*. 




u a MiitwqiMDCtf of "dnvtiii^-" J^Aturally tbr 
lou^r the BuspenHon wrthiti tke period of Ti«- 
bilitv of the ovssnifntB the gnMUr the diaiKt of 

DrupMH of £<a1jT8^ rtc-, Hrt iliAclLari-'Fii mto the 
«:r thrt^Ufh (ou^hinpr, sae«inir- loufihtcr, ajid tvcu 
foiriblk* *f>eakii^. This flow not occur with onii- 
Dary leepkration. In cougfaitig droplets may be 
Mrriad «d far hb thirty f«et from thjfr mdiridual, 
and lli«y way Ijp t'arrii?d trmJi farth(*r by eilnUM?- 
ouft cturcnta of air< Such droplcto mny remain 
*iiGp«nded in the air for approximattly Rt: hour, 
byt the period of their vu^peiuion depend* on their 
t'txtif Uic irei^'!)t of the orpaaijnii they oarry and 
thi* d<Tg:n*r» of mfliitliirp in tJir air la a drii-r air 
th*y becomt dcsiccat*d more r^wickly ond nftct dc#- 
iooatton fall more rapidly. 

TjBflcbUclienlco. and atw FTeymAnn, investf^nt^iT 
the diftseniinatioD of tubercle bccilli by coughing 
fn pnlmonary tubpr£*nloiii»!. In -^O p^r rrnt, of the 
caa«! guinra-pige which were placed even at con- 
«]d«Tabl« diatancea from the patients eonh-aoted 
lnburt'ii!i>*ie of the lungs or bftmoliinl lymph 
gUnda. The bacilli have been dcmonMmtcd mi- 
cro*copic8!ly in such droplet* by nnmCTOUB oh- 
Berreis- Leprosy bacilli are canied aijialariy 

On acf'OUDt of tIkHr c^onUnt In inuf^in tV> drop- 
lets adhere cloacly to noHd ?iirfacea, wherr th^ry 
Aooii dry nmt becumr hnrniI«Ep ttnle^ they are 
d»)oigpd iiy fioiiif vinlencft 

When contained in «uch dry droplets tlie tu- 
horcle baeillue liv^ for about three day^ in (hG 
light and eighteen days in th« dark. Moat other 
or^aniMna* except the fpore-bearine nnd lho« caii»- 

unovhBi iicftCTtoy». 



it]|t *oins of tbe contn^bu^ ^xantli^nnati], die more 

Th« condilion* for droplet inrection. thei>. oiet 
IB tli« main, a« follows: Fini, tbo micro-organ- 

ind vtrvklt--iit c'onditioTif and m ^ufTtcicut quuntity^ 
from tbc re*pir»lory pn^ia^jt of Ib^ ptticnt. SpC' 
^itd, ther iudM be able to lytain life and viruIeBc« 
fiyr e |?W4icr «r l<«a period of limo, aft*r 
b«iag libt^nilt-d in Lift* «kj\ Thtnl. iln-v uiiir't In- 
able to tir^ »^inc portion of the rcF|iimtor>' tract, 
ar tbff gHstrn-int^tinnl trncl inrtirectlv from the 
rcflpimlory tract, as an infection airiuni. FouHh. 
iht adnnt of i flitSK^ptiblc person vithiii Hit jjobo 
uf infii'tiHl [itrnoHphErn- tt^iirh MirTnunil* Un- pji- 
ticnt dnrinK the period of riftbilily ard Tirul^ncc 
of the excrete*! orgaDTama. 

In gvn«ml th? »«nie prinnple* aUo apply to iluRt 
i&fectioD BC far as it oonoerna the ordinary "air 
borne** diftfasea, 

TJie qucfltion ia couuiionly laised as to whkb ii*i^u*e 
la the more bnportant, or more prtnaloct, duat in "'»'"*'■' 
fectiori or droplet infftctuirL- AUbuugb t1 jk Ibr 
tciidcnc->' at present to %mii^ a miTior r^lc to du^ 
infeotioQ, it untiiiesTtTf-nfthlv it f>f importftnce in 
cerUtn ilueaseH. parlicularlj lit tubea-ulo&iti. The 
aituatioo may be vonecircd to be as follows; Id 
Illation Id diiu'jupt miuit'c! hv mit^rrt-organiama 
whicti batf little rf^&i&ttince to de^icf^tioD and 
light («.g'-, plague, inrtuoria), dropltt inftt^tion, 
Emptying proximit}' tu tbr putic-nt^ ie mnrv liknlv 
to occur than dual infection (as in oecupylnjz a 
room Tasted by a putipnt a longer or shorter pe> 
riod preTionel^). Conf^niing thoee cniiM>rl by of- 
jfaniuiM which htvt irrcat^r re^irtance to deeJC(?a- 



tlon and ligliU ai) 1:1 tuWrcuWis^ the imporUni^ 
Alt iivt»t iiif'Xtiaii Qp|)roMTtifltos, tfiongh it may Dot 
rf|jiiil, \h»\ uf ilrti|jM infrt^lifHU 
waifir ■• Ju»t nn the air b tlie piJut-ipal iuecliiim of con- 
"^Sirnq^ vtyaiict' for tiio jcroitp of dia«aa« diBcnaW abo^-e. 
V4I i^iiiL^iniitkuUij wiLirr pln^ii nn m]|HirUiit. Imt tiut 
tIi« fck\ (lart in the trnn^mijulnn of onotiicr ^^ronp. 
Typhoid and parat}'plioid f^vor, ohoTera nnd bsciU 

Epidemics nhicli atiB^; it thia way arc frequently 
cpokon "}f a* "wflt£!r-bornG" epklemira. SoTiictiriie* 
tvphoiJ nr;*l i^hi^lem ajv <nIlcJ "wuler-borae'' i}i\o- 
ouu, but opidmnitft nrc fu i>ftou ir«titV]t«d nud 
maintained b> varioui kiad» of indirect contot-t 
\\\nt Wvt ap])e]l£tioi} ib oDe-eided. 
cviHiKifiibii' i^^roR otx^ntml oonditionB ar^ requiied ia ord^ 
llint a diirtute iritt> lip nioit? or Ie»fl Imtijtuatly 
irftaainUtcd throujfi: wutcr: ^ii-til, tiic diachar^ 
of th« organicrnsi from tlit^ liody of tht^ |)ntirnt in 
ftich form t1)ot iJicr may i«ach a water supply, 
Socondf the Ability of the orpanienia eiTher to live 
fu[ H inodt-iak' Ihi^^iIi uf liiiM^ lu Du- watci, or in 
Ejrohfrrnic in >l. without lotijnR virulcijcc. "Iliird, 
th? ntiliiflticm of tb9 gn>:trr)'i'nl0¥(inji1 trnot tho 
u|ipci reapitaltTV tract, or the luniiB indii'cctly 
fiom the latk-r, Jii an atrium of infpHion. 

TJiertM mnditimi is rendily renli^ed In t}i« dia- 
easefl mentioned, iuaamuch aa the micro-organiftinft 
aro diftdiarped m Jflr^o iHirribcre wilh tTi<j feces. 
iitul hU), in the riiJtc of IjplnjPid and paraty|jlicid, 
with tho Lirinc 
<i..Hrfi>* uc All tvro* of ti-nttT !iU])pli«fi may bn ^rontaminat-'il 
iivu. l>y ilie*e rscrettonn- Uhen the water of ^ li-nn- 
munity is taten from a siresm t^e lottor may bi* 
infrt'Ud ly Umj sewage of anoti^er community 




bi^W lift ihe §tream. or by the iJiscbarj^t^ cf tvcn 
a AtDflc patiriJt. Tlic tlironin^ q! typhuid tlijt- 
charg«c un thit bunk of a utrcrtm hag resulted in 
ftfntp vpjdrmim. IJcjwrToin nin^ W infi^^ sim- 
ilarly. In vomc icstancc^ n dty whidi <1rrivi?s itf 
urat«r from on inland lako ako cm|}tioa ib aexvcn 
Into die wtme lnwly of wahT. ICveri when the eew- 
age outlet ia ^uUe reiiiUi." fi'om Ihc vrntt-v nuukvj 
ttirSovo curronbi, n^ cnumd by the xrind, ma\ carry 
Wiier, nn<i h^iic*j inf«ctioD. from the f-irrn^r (o Uie 
Utter. In larbor* the water maj becoiut inftcted 
from the sewage of a ship vtiicJi (^fUTi» n cnac of 
chofeni. Streams have b£?en pontaminate-1 by 
w«>hii]^ in thfm ifie ^^oilnl lin»*ri of jmtinjts. When 
«xcrettDiiv are tbroTvri on t!ic grouoJ \}\t iniirro- 
OTgSDifnns hav« been carri^ into wells by §urfdoi.' 
wnUr irtim whirli *in*ill i-fiiilemics hnv*' Hriwn, 

Tlie Tcry oivnrrpnrr of witlei-hnnie epidt-'mirs rLabiTiiT 
iDdicnto that \hc nticK^-CTgnmstxis concfTiivd ])vc 
for a longer or shorter period of time in ovdingry 
walprv. Vannuft tirUtn inllitc^icf tbi»ir lungrvilv 
ID ntti^r, and tEselr perfli»rtence at tli« point of tM 
con turni nation. Purer wutors «rt not so fnvornblc 
for thr life of t]io orgBrUmH of fyphuid and tbol- 
«rft as tbow which cootaio a c^rUm amount of or- 
ganic matter and palla- On the other hnn*l» nn cs- 
oesf of crf^unic mutt^^r when nccompanivd by many 
i^prophjrtic organisms also tJiorteus the life of 
tliwc bodcnn, pnrticularly whco in stagnant 
waiCT; and thii* prinnpde m utxliacd for puriliou- 
tion fit ftfwngp m ihot* svf)t?mt whioh in-olTO the 
tiae of »(^«ni2c l/inkrt, A rapidly lowing Mrcom 
Rdlurally reaullH in puri^cation more iinickly than 

If! yVm**" 


isPKCTJoji Ah'D riiMt-\ny. 

m M-Rt^r juk) milk «rr girco id the toeti^QS oa 
cholen and typhoid. 
-M'ltivr. 'nVftTvr-brm**' «pii]«itiicft Mre chinrtCTifttic in 
''^.i^.-'i- tl^i^ that icr> manj indiridnals ore atrickea sud- 
■3pij*D>i«'-. (l*iilv and ^muHfineoit^T and the OQthrHik U, al 
iLr»t, limilrd to Uium: tvho are icupplied bj the in- 
fected vraUr. ''Contatt'' q>idomic0, on the other 
hand, progTcee ticnrly and irrr^larlj, alUjougli 
Ihey niay finally re«i large proportioas. Nat- 
urally an epidemic begun bj contaminated wbIct 
may bf^ nininutinnd br contact, and continuance by 
conlAct aiznin olFor; opportunit;^' for tlie froah in- 
fection of water, millc and food. Tbe viability o( 
miCTO-organi^ma in iht ex*^TvXa, after tbe diacfaarge 
of the Ultc^r, U importtiit, (joUi from the stand* 
poirt of water infection and that which occura 
by indirect contact Utfelniann determined that 
typhoid bairilli may live in the dejecta for many 
inonthE. and, at lca>t imder aome eonditiont, the 
i-boTGra vihriM in the feecf i* viable for two or 
tlueo weeks n,ubfli*ch). 

An *tatcd prcvioudy. difcuf^ee vhieh arc peculiar 
to man may be diBtntint*>d by mill; which hns bwn 
contaminated by conialescent* (as Jn scarlet fever) 
or by "coirier*/' or bj- si^me others iudireetly from 
timte, or by itiffH^l wnlrr used in \vn.t]iinp: rnii- 
taincTf. Kpidomicfl cnitscd by infected milk are, 
in minintiire, nimilar fo those ariiinp from a con- 
taminated water supply, thrir dii^tnhntion cciiii- 
ddin^' wtUi the arc^a of oonpumption of the nitlk. 

Other food suh^tanccf net na eflriying agents 
only when they becoiiie infecle^l ucLidentMlly. nv h\ 
fi\t», vvathin^ in coDtAciinaled watcn or hy con- 
vnlwt'entfi ami '>arri(»M." 

I . 

ct}^vEyAxct: r^r vujruiMi. etc. 


TraDuuisbian bjr direct uod iodirflct contort arc cn-i-ri 
MiDCvhAt in contraM. In tbe former actiiiiJ |)cr- 
«oqb] contact iAVtst itUct^ between (he ^Jck and 
bcAlUi}'! 04 prcvioiJfily «tAtc<i, ia;d v.^ iUudtratod by 
^*DOcrrTbeA and typhiltg.* I'pob*btv miuiy of the 
mftrlionic ^lilch axe conveyed through tl)C nir nittj 
4J»o be ocqTiirod by direct ccDtact. However, a 
dirtinction in thi« ca«e hAk uo ^igai^eitDce, ainoe 
actiul coDtact without oxponirc to air iafcdion 
eo^ild haHiy ooeur. 

Jndirtct contact, oq the other hand, impli^ 
tntBUnWioii througii tliL' ageucy of ao icttnue- 
diat« ponoa or objoct, Speokiug stnctly, convey- 
anoe from p«rvon to p«reoLir tiirQugh thi^nir, wnlcr, 
or cT«a by icfiect^, com« vriihm Iht tlomain of iD- 
diroct oonlAct, y«l U^uir methods arc ao specialixed, 
«0 obtrofliTo BiiO «c con^Untly utiliicd by certain 
£r>ii|« of iiiicro-organi«nia that t^y dc^nrvo tho 
Mparati* oomderation usually gi\en them. The 
todcncy ien a <:orrcct one to withdraw from the 
domiin of iDdtrect contact Aty mefbod of trAHR- 
miaiion which rnn be spoken at more <^Jncr(?tely 

One coold not liope to inpiiliin nU of Ih* po«i- 
ble ohanndf tlitouj^h which an infection may be 
oirri«d Indirectly. Ther^ are great variationa in 
clidailji. "Crtrrjing n diiu-nsff in onp*» rlothing" 
from piACc to place; the unc of the toya of a diph- 
thmtac child ; wni>hiDj(' or handling the linen of a 
vhoL#Ta, typhoid or dvfipntery putient; opciqjying a 
room formerly used by a p/itient having trniTet 
fffrer or ttibf rculoeis ; tlie occasioual tranaf(M of 
«ypl]iii« by the driaking-cup or the dontUt^s fcr- 

r«Bl«bAl irHnafrr bf drfakliii: cuti* i.Di1 lDiirnm«ora: 


r\Ftccrios A^D tuurviTY. 


■I AH. 

&iuijG:TM]r through contaminalion of dr««&i}i^» iini] 
of oih^r infections from pnlifrrit t^ pilifnl tbroiiijh 

imcleftii ui*truHieEl* oi- liands; lhc-*c nrc cJiompEc^ 
of coavovuucc bv indirect oontnpt. 

As some of them tihow, diKCTspti whirh ■« hn- 
biLimllj' trauAnuitvd Ihiougli the Air (scarlet fever) 
or by wfllcr (tyj^hoSd. cliolora) may alio b* 1ran«- 
(oryft] hy iiulirrct, ttmtnrf.. 

In the strict Koolojiical wn^i: no fonn of tmm- 
misEion of an infection from psrent to offdpriug 
cjiD he vhwed na truly bpreiiiton, sinw iMlieritnticc 
tontcriif onl^v properties which arc inlicrcnt in the 
gwm c*;!!* am\ flioir cliromiitfii- Mioro-organJftrny 
ore foreign and their inlrodudion ii^ the germ 
celle from th& parent can only b* eoasi'Jere^l o* 
iimJmituh II. is, lIi^jj. only for the aake of cod- 
vcnitncc nnd fot lack of a moic o^oot term that 
Ihp inhtntnncp f»f iiif^flmns ii; «j>nki?ii af Thi^ 
distinction ha» been strondy cmpbnsiT:cif by Hnn- 
sen [ViroL Arch.. Vol. ISO) anct hy Lubarecb 
(Ibiih, V(fh 124), .%nm uf ihe TiietabiiHc ilispHitfs 
JUid fuDctionu! HrrnrccTrciit3, on the other hand. 
may be Imly inhoritpi, nr, perhnpn better, a ter- 
deucy or predifepoiitioa tj them may be Inlientcd. 
AUo, it la very probable that euFL^eptibihty, or, on 
thr othm" h«nd, n^Misbiiiii' tii annie pnHir-idnr infeo- 
tirjfi. miiy br inhpntfd, thug nccoiiotin^ for *\\t 
frequent or rsrt DiH'Tirrence oF ^onio mft^ctiorm in 
n given facixily. 

Hijcn diftcn^e of the offspring ran be refi^rred to 
fl primnry inva^inn nf the g<?nii colls (ovum or 
Sirt'iTn t'tfllel hy mitTO-or;rani5mF it i? Mirl l^ hove 
ori^Qaleri hy *';rftrm epll infection." H is not 
d('fiuTti*ly known tiiat this type of herediury trans- 

insnjii CELL t^'Fi!CTf(^K. 



^_ of tJ 

iniMioD lakes place id ivian. uDt.l tlic UkcliliODiI of 
ilA occurretiec coiiM be proW only by flndlng tht 
nakro-oTfnnistJiii acTtiialJy within the ovum of 
tpenn cell, 

npfinitj* rxnmplr* nf Uii* Up* of trHUHmWun 
•re found in inpcet iifc, pftrticnlnrly nmonir ticks. 
The piroplflBmas of Texa* ferer unh nf Pho<^flsian 
fctfr of caltle, tin* :<pirillum of South Africnn 
tick fcTcr of mntit nriil the viru* of Hncky Mniin 
tafn vpntied fet^r nr-t? nil tritnamtttcMl tn ih^ tnr- 
ne of Ihe gentration throuirh infe/rtion of 
Uie ovii of tire eorre*ponflinp tSfrk*. 

Since it does occur ir oih^r forrn^ rjf life, it 
would not be mrprisin;: if it abo occurs in moD. 
Id tiiftt form of inhcritMl svpliili? in which tho 
child detiTefl the infecti^^u front llic futherp the 
mother apparently remaintnir uninfcK^ted, the virus 
rtity have been ialr»>(li«i-fl Uiia iTu- tiviim by mran* 
of to infected fperm ceil. Kvrn in Ihi^ rane, how- 
9f9r, it 16 rirtuAllr inipOF«thle tn nilo out the ^xis- 
ce of a latent infection of the TuolK^r. And it 
infeetion dooa esiet, the t^iirrwhcle* inay haxrp 
rettrhoJ the emhryo liy wny of the phiopiiin. In- 
stead of Ihronati the cvum. PcfcwibU the leetntlv 
(llceoTered teift for (7phili4 (fixation of eompl^ 
mmt) V ill Ihruw stiriie li^liL ou tl'M itliMw nf in- 
licnted (Tphilii', tiiKc it rcndrri pn*flih)c thi? d'laz- 
no«U of th« iViPPtife in Ihf* mother rpgnrdle^s of 
poaJtiT^ clinical manifesto (ion^. 

It i* oqtiallyr or perhnpa more, Tinocrtain os to 
whether tnhpTculosiH u ovor inhprifi^H flirntmli in- 
fcrtion of Ibc ipenfi celli'- TuhercTc Sncilli hnre 
b«tl found in the ti<«ticiilar tocrpiinn m hoth man 
and nnimaln. Tn tiieh tnim the luTw^n iilo*i( [« of 
an Adrauecd type, reeultin^ in cnrly dootti. Etot 



ixi'jsvftoN AX& tjitttuf^m; 


if Bom^ of ihe bacilli uere artnall^ vithtn Uw 
Apemi ciills and cajole of iDtroductioii into tlw 
ovum throo^h tlicin, tho graii pr«poiklcTtiice of 
thn HptfrrnAtoMMi iivu-r thn bunlli rvm^rm iiifc^tioB 
of the ovum iRtproboble. In oac euch c«i« (lartncr 
estlmatod tiiG numerical relation of the bacilli tn 
tlif; npcrmato^oa aa out* to S2.7 mUlionp hence the 
itnprcgniiting cell would vorr likely be au uuin* 
fecf«l one. 

It has flonictimc* hten woumcii tlinl leprojiy m»j 
6** transmilted in thie way, but Jhers* ii no rtrong 

Infcctioa of tbe ombrjOj from the mother, by 
way of the placenta, has been *3einon&trated <^pcri- 
mnitHlly. nai\ e»*:oLinlcii"[l ("Unicalh-, uiimistjikHbly. 
Upinion* differ n* to whether nctuol invoh'eniL'nt 
— r *, infertinn or defect* — of tJie plaoenta la 
prerequiaitti ti> ibe pae^age of mictO'Ovg'iniMiiN 
from the mother to the embryo. 

M. W'oHT, tm the Imais of ej^perimental work u'iUi 
the nnthnuL UicilluH^ concluded timt the iminjured 
placenta ie an offootiTe barrier against bucJi a 
trB"rtf<?r If wa* HuppuBed, however, tbat injuries 
ot the plucrritn which rpsulteH in blecOing-. thus 
fjitabli*hing a tpmpftrary conu^^^tion hetween the 
circultfitJoni^ cpf tbe mother and fetus> &« well as 
oth<n- iMiooa metastatic in charaetor, couM woll 
reauH in infection of Llie embryo. Mnny others 
also, on tbe bnsia of cxperimcnlat work and the 
*tiu!y of human mflterial, ooneluded that there 
must be rcco^JEoble lesione of the placenta to 
pramit tronsftr from mother tc child. The bo^il- 
Ina of chidcen rholern, p. member of the hemor- 
rhngtc KcptkemiA group of urgnnisins, rnuscs hem* 
orrhagcs in tlie placenta in onimaU and \a trane- 




tnitt<d to tht ctnbryo (MrItoz). Tiilietciilosis oc- 
GwriemBlly, itnd KvphilU tcry ofton, attncfc tho plt- 
CVAtfl ID man. Iei n nuniW of in^Unoes fHii&p^ 
hart betn bom with the truption of jrmallpoi 
deriwl from t}io mother tnd the irnuifer of ty- 
phoid bacilli through the placenta has been ob- 
E«rTcd ccc«»OTULUy. SimiJar trAmmi^ion in ninii 
hat h^n notnl in relation to anthrnin piieiimoniiiH 
itcuncnt fcvcr^ and iofoctioDn with the pyogenic 
coccL Abortion*, due cither to infwtion or intox- 
iciiti<iai mAjr occui iluriiig mo^t of tlic acute fe- 
brile mf«ctiona. 

CoBtiflTT to the 73CW expr^ceed above, Banm- 
fartai. Biich-nii^chfeid. Lubarsch auJ iiianv 
other* coBceir^d thai a jDrecxmtinff injury of tht- 
plarr-JiU » mit n<«enlm] fitr iraiiHfcr; Lhat the 
micTD-oi^nisme. cepccially v^hen proeent iQ tbd 
blood in «m*tderable mtmber«. aa m anthrax, may 
"(froii Ihiuiiich" (he placetital vesBcin in the JibBPiici: 
of, nnd without oaiiBing, nnjitomicnl losionf. 

It ia extrem«lj probable EJiat both views are cor- 
rect, but perhaps in relation to diiTcrent typci of 
mioroH>rgiini'ii]p. It has been dcmonptrnted lunny 
timea. cliDimllv nnd experiTnentally. Uut tnberi?]e 
badlli will pan through the intestinal mucosa into 
the adjacent lymphatics without cauaing loAionc 
of the EDUCoia, and, althou^i LIef conditiona are not 
ideatioal in the two strui!tur<^s (mi^mtioa of wan 
daring eell* thrun^h intaKiJial w«llf), the ot-eur- 
rcncc in one »u(ri:c*ta it* possibility in tlic otiier. 
However, the oxiit«nca of tho phenomenon is eo 
ttioroug:hly eataUlisheil as to render tlie i^xatt rTn*ch- 
anivm n more or low Mcocdary matter. 

It It an important tiioory cf Baumcrart^ii'R that 
tubercle baeilH whloh are aeqaired during fetal 

r.\r£vnof/ aku iUMCMTT. 

life niity remnin UUat nQtit pubcrt.v qikI tli 

wlmn tlic unusual Tcei&Unce vhich U coiucidont 
vvitJ] rnpiil ^ruwtli liaa milsijeil, tlie bAcilli inu! 
tipljr Bill] tuWrcutosis manifesU itself- lie mp- 
pojH^ Aim that an mtRrmcdiatc j^t^ration niaT, 
^vilhout fchow'iii^ luberculo^ip itself, tmti^Tnit Hip 
(li*eaiw t'j the iip^t gen <^rn lion lUrhrntpriruiitttf/ von 
Utnerniwttfn). ThU would wr^-m to pn^ruppo»! 
the ociMjrronce of ^rm^oel) iafeotion, but perhups 
ikot necfi^^M'ilv ■!■, Ak hiiriiig ii poa^iblE? In^riug 
on Bauingnrtrii'B hypollie^U, it liaa been fouiiii l>v 
Harbit?;, bv AVochselbaum nnd ofUars thai tubercle 
hiirilli, pnrticnlnHy in tliildi-en^ may t^xijit in Uie 
IvrikpTi ^lanil» wKliout caueJn^ a natter nical chan^e^ 
Tbift view hfl? seven! strong supporter?- ftnd it 
ii tbou^ht that tbo bacilli may retiiain latent in 
anv portion of the body. Tliat bereditary syph- 
ilis mny remain Intrnt for mimv yeftr» ia veil 

On tile oHier bRnd, It is more generally believe^' 
thnt tubertuW]4 in moai in»tAncf« iit n po^tnutel 
HC<^niriitJon (Kocb. Comet and others) nmt ra- 
tionnl prophylaxis nsdirfllly must be bused en tlii= 
i\mi!(^ption, Kxt^'U^ive involvtinrnt of tbc livpr 
nnd periportal lyiiipb glands is dmracteriatic of 
tlie plnt'L'nla! transmission of tubcr(!u]osi^- The be- 
lief ifl oa-aaionally eApressed tUat leprosy mny W 
inherited, poesibly titroLigli plneental tran&iniaaion* 
but. III view of the non-suBceptibilily of animak 
and failure it* cullivsLe the bndlhi^, tht* question 
cai^not be Uken up cxpcrimentiilh'. The pos*ibii- 
Hy of inieotion of tlie embryo directly ivatn the 
father diiriug ooitua Is 4]iHeusseEl, but there is no 
detinitf^ proof of its occurrenct^. 



It is (onceivabie that micro-organisms may pnss 
from the mothet to the clnld by way of the blood 
through the placenta at the inception of labor dur- 
ing an early stage of separation of the placenta 
from the uterine wall. 

Infection of a child, as with gonorrhea! ophtlial- 
mifif during delivery is not regarded as an e.\- 
ample of '*inheritance" of disease. It is an extra- 
titerine process, a congenital infection. 


11*1 V of 


(C] DiMcmination ind Trarvuniasion hy IiUf€l$. 
A. Diitefitiri&tiTn. 
Thp dcmcint^lrution that lasectti may plav a r5le 

in the trftriHmiuton niid irAintononee of inf«ctioDa 
Jalw from tlje work of Smith srid Eilbournc, 
winch disclosed the Tt^lation of tbe ii^k (Mar^arC' 
p-ng annultttuM) io Tl*xaa F^ver in cattTc- 

Inscria mny net HirEtirly as diaspminnltjn* of 
rims, i>r ns the o^ntd of ncUial inoculotioii 
thrcnigh thoir bitw — i, e,, *i»j trflnKm ithfli'K- 1( iw 
lEripnrt^nt iv Vt^cp this Hi^Urirtioti ui Eiiiiid. 

In their rSIe ns pure dissemiuatoni they may 
carry micro-organiema from ore point to another 
on their feet, moTith perts. or in their iiit«fttina1 
contente; or» they may act as IcmporAiy host^ the 
microbes proliferotinp in their intesliiia] tract bti"3 
Bubaequtntly LcIdj; deposited with the fec^» in ir- 
f?rnnii'd nnmhfni, at ■onin tirw pciint- The first is 
pure mechanical dissemination. whcTeas in the sec- 
ond a biolo^c factor enters, that of prolifcraticn, 
And it may be spoken of a^ htologienl dta^emiTin- 
tion. For example, when flies cam typlioid bacilli 
Of oJiolera vibriCM from feecs to food, on tlieJr feet 
or nionth parte, or trihercle baeilli from sputoTr to 
food or other objects, this is, of courw, a piitely 
mechanical proccsa. It it^ould be complicated by 
the biological featijre, however, in enie the or- 

fL\ 77fa.vtfJU/ffrf;oA 


gaowtn?. tftar iBgntion by the 6y, tfjcn multi- 
plied, aud were deposited id larger nunib^n In 
^j-8pocka. It ia, indeed, a dtl!ii.*uU pctint lo deter- 
mliM vhctlter or not pry>ltfenition r>f thoM mioro- 
i>rg<Uii«aK ActnftlU tahea place \a the iiit«stiDe» of 
t)i« &y, Obiervationg by SpiUmen and Hauahalier, 
Hofinann, C«lli, Hajwanl. Lord and otlien liave 
ahovrn coDCIusirelT Ibat houdc-Hied ingvat tubercle 
bKilti from the iputum of patJoclM nnd t^vtrdc 
tiiMa io tlicir fecw. The cbjcrration* of !-oril' 
evgpCfit, but do not ftctiistly -pro-v^^ that the bnciMi 
nialUply in the intestines. U has been demon- 
dtnt<^ KTcral tiin&^, by inoculation into guinea- 
jn^, that the bni^illi in thi* fly-»[je(?)u an^ virulent. 
Tbe tpcckft ^ry quicktj and tlicrc is littk danffer 
of Uw organUm£ laking pnrt in duit infection tin* 
Ie«a the »pccka Are violently dislodged, and they 
die In a few day*:. On tlie otl^cr handt there may 
be a real danger from tbe dejxi^tlion of tbe ft|>i?ch» 
on food (Lord), which BUgj^ta a point in pro- 

Similar ijumlioctEt nrn raixi^l ii1«o in tbff rrlntinn 
of the fit tc lypboiti, cholfra, rlyaentcn" ^nd pJa^e. 
The imporlanw of the fly in the merhamcal dis- 
sei&ination of ty|jljoid bncilLi, r^ulting in txiioa- 
s»on of epidemics, a now well eatabliAhcd, »s illu»^ 
tnted by Ur- oliwiTfltiori* «f Aliiv Hjuniltiin. nnd 
Ihr intpiiry into the prcvulom'C of typhoid fever 
in the American Iroopis during the Spaniih-Amer- 
ieau war, Tbr conditionH arc urmiUr in rrlntioti 
to cb^CTa. Conocrninic d>T5^1^fT it ta con^dcred 
prohabk that flies arp n factor in d I'trihutinn, nU 
thOQgli the point baa not htvn positively demon- 
Itritftd, H b itneertflin ubKbt^r the or^^nitm* of 

]. n*fart« 4f tbf UanifhnBftl* aev««l BotpllftL 


/,\7*ficr;o\ ASD iJiifW/ry. 

tvpboid end o)iol«rA pro]ifi>rnt« in the inteftticket of 
tTie fiv- It ^4?erri» not UDlikcTy in the cam of tj- 
phoid, iiiaftuiudi ne Ficlccr'' found thein in Ibc fly 
Ututy-Urrt't' (In* oftLT n 5<>od on the bftcilli. T*U' 
luki* oiltivatcd cliolcin vibrio* fTOm tlic$ which 
wore taken in tho dn-fl)LDj'3 of pntiGiiU. 

It *^tnK probjiMc fbut flioc, in *omp inBl«nriiM, 
m^y distribute plague becilli ftfUr tbev have them- 
aelrce hooom« iofooted by f^-Win^ on the apiitiin: 
of jincunmini" phHchIr ur ofi tbi' rndaveni i>r nit» 
dead of the drscoH*- Yer^ir* found plngue bncUH 
in tlien dying id n tdboi-Atory in which plngxie vsfit- 
beinjj itudi*tl, nud in NuttalTs^' t\periiiient* the> 
bcoftiTif iu/eoted hy fet^mj? ou dUeaaed cirj^aiiB. 

Th^ fl^n, on the other hand, appeara lo Act both 
oa a d)-^emiuator anJ afi a trunEimittcr of pln^c. 
Tho huitiun Iku. at I<'n*t tvo epm'iff* of rat fleaflt 
Hud the ilew of th(> dng wnd ani n?fldily become in- 
fQCt^d by feeding od rate during the 9Utge of aepti' 
eeiniA in tha latlir^ tlie bacSUi niutUply for a few 
doys in thr-ir utonmdi and inlr^trncfl, and art ex- 
CTflted in larije mimbprv in their fec*>s. They are 
able to ooiiirTini) it-ale tlie diHeit>»e to other animaU 
by biting for At Icaet three daye after thdr iiif«o> 
tion, bitt in a iibort time Ihi^ bacilli diftaj)[ieai- from 
their nlinicntory tract nnd th1^y lopc the powov ^f 
iraneniie^ton, Tfie orgBnUnis. whioli nrp pxrreted 
in Lhr-ir fvcvK. arc vlndenl, Jiind are nbli.' t^i lu'iHlue** 
infection through vcrr small abrariona and 
through th<j minute wounds made hy the bites of 
thvtu* in*i*i*i^. Th^ ilepoj^iition of bacilli In tlie feoes 
of the flcrt on tJic pfctn of a porson la u que&lion 

2. Arch, f- Urn. IP^S. lU, 3tr, 

H. ArfTi f. Ki^hirr* 1] TVoiifnhriillf^D^- VfebruirT, l(i04, Till 

4. Aon il4- riuil, r«il.. 100«. I, ffi?, 


of diauxobudoo, whereas the iojoction of the or- 
gtDiiin^ throuffh the prob4>»(.nfi ia one of inocuU- 
tlon. TTip iirm ap\n^rv. not Ui uciittrgo a j^eil- 
cnli£«d mf«iioti with the pinicac bocillue. 

It ift po«eibla that tits may b^con^e iTifprt^ 
with piBgue alfro h) Ih? enting of fl^^ns whtfh con- 
Imin bttcilli, ftjthongh thii has not ycl Wn demon- 
KtrntHv Kxjurrinu'Tilailly Iht- ilifiMat hs- been pro- 
duced in rnU b> feeding them infected tt»\iOft or 

TprJhitaJri fllw found IhRf, tho liwlhiig behwi^ in 
« loaikner ciactlv HmiUr to the flea in the case of 
phgne. In aolnal epidemic*, however it twms 
prohablR Uiat thia iiiH^I. would bi> (?cincerii«ii onlv 
ui U)e tnuumimon of the dieeojic froiTi man to 
miiu, Niid ncit fmm rut to nmn. 

Wilh tlic rscfption of the Ust parAj^mph thp 
above eonccnis the mere dUK'minKfi(>n (if miero- 
0Tgvii*nLii by iniwct^, :\* iiotr<lt tJie dii^enKe^ ooiv 
oemed Are baclorint in nature rnttjer thiin proto- 
toan. Pathogenie protozoa may he excreted hy in- 
9t<i\ bat, if »c, the c^tui appear* to he without 
practfcal ftij^ifieELnco^ L'ithcr bouiu*e the or^nniiBnii^ 
■Dp not rinMe wlu^n excrrtinl. or nii? dot in a iLljigp- 
of development to render rhcm infective, or, what 
w more probable, that they ftnd nri infeotior^ 
atrium wl^n in thi» t<*ndilioL. ThoM proto^oft 
wbldi are tr«nainittcd by inaeers Liinally require 
■irtiial inocuUtinn in order that Lhry may c^im^ 

Onr Icnovledgo it b> no meant complete on 
tJhe tnbjeet of in»ect traniiriiiujcn, ae n whole, al< 
tfiongh the ''■'entin! fneta have l>cen workrfi oul 
ilk i number of inetancee, a« in Texas fever, mmp 


«« ryF£0TtO.\ AMP iUXUNlTY. 

other piroplnsmcses. nnd in malarifl. In somf io- 
HtJintM'^ it is the niJcro-orgnniBEi whkli \% untnown 
(yellow fever, dengue), in othen tbe quefliiuu of 
inhentanoe id the ineect (ti'vpano^omiaaUj . in 
otli«^]^ Uie rtlnLJoM of Iho tnstict iiti^ the A\^ewc tx> 
hnpts clhci than man. etc. 
irj>uamiM**iJ D:seosee which are transmitted habitually^ or 

tinctiFc cpidcmLoIogic fc^tur^s. Maiarin occurs in 
swampy Tegiona in which certain specioa of ^do- 
pkeles abound- Tlie diftrllmtion of >cUow fever, 

and icdtH^d of uH t!io taswtborn^? dii^asoi!, coin- 
ritlcF with that of the inP4?ct'* whirli nr^ fcmemed 
in the distribution. In the temperate and anbtrop- 
iral courttiw snch difleaeee tend to pre^'sil in the 
warmer months and to diaappear on the advent 
of froflt or oooler weather, an ev^ut whidi is cor- 
relhtetl \\-xX\\ t!ie Activity or innrtixity [>f the insects 
during these eonsons. The Indian plapiic commiB- 
aion Unils Ihnt an epidemic wanen when the menn 
daily tonipcratnre is l>elow 50* F-. prcfiumably be- 
esnae the flea does not become infected eo rtiadily 
rnjdei this condition ; tlfe rats die before Uie advpul 
of intenEe septicemia, and without the lattor tho 
flea is less likely to become infected- The Ilea 
mar also be lei« likely to feed generously in the 
cooler weather. Al^o it was found tliat a mean 
daily luinperuture of 85°^M*' F, coincides with the 
decadence of an epidemic, and in harmony with 
thi£ it appeorg that the lieu remaJna infectivi) for 
t miieh shorter time at this temperature. When 
Tirluailv all Ihe rets of a locality hnvc citht-r 
been killed by plo^e, or hare retjovered from it, 
those which remain are for the most part 
iniEQune, and the conditions for a recrudescence 

iirsBOT THAS'sutBfiro?/. 


tft AO cptd«niic vrill Dot be rfpe until a q^w geu- 
^rfttion of raU W Wn bred. The immune 
raU do not harbor pla^o bacilli, and hence 
^aonot infoot lli^aa. Rock\ Mountain spotted 
ftrer prftraila only in the months of spring. At 
thi« timtt iho tick wLtdi Acts as tmnsiTiitler Is lu 
itii ndtiH iif'ge nnr) renilily fc^la oii miin nii well as 
on otht>r aTiimfl]«- The larval and nvmplial Btaf^a 
appi<ar at oIIilt seHSciDs, aaJ, aU1i^>ugh their bites 
■re infcctiTc, thcj nirrly feed on man^ either from 
Ucic of opportunil^ or hwaoee of i preference for 
oth«T ho4t# during the«e etagea. The observation 
of Oarttr. that when yrllew fever patients are first 
Unportfv! into ■ xjffw dinlrifrt a flelini(e f*eriod 
(tWo to Uiree weeka) elspM^ befoie new cases de- 
^ekpf fii]jg;;eated eome novel niodo of ti^an^miaeion, 
which i-vitrittmlly wtn pnivrd tnic wlipn Reei^, Cnr- 
rol uul Agnibontc prov^ bv cxpcti mentation the 
comectn^tf of the mo&<piito theor>' of rar]o*i Fin- 
hj 4Uid tfovhid oijt the detfltlft of tTansniiBBifm. 

Por eome tim* it was fiupposeil that msects 
tranftfrlt otlj UioH' di^'a^es whtoh are eaueed by 
prototoaii ot^nrrRns This iniprr^^iiiii nn^i^c frnm 
tlie SMtt that the first examplce of dcfimtely proved 
faiuot transmhwion cone^rned protozoan diaeaaee, 
M T^ng ferfT (jl piroplasmofiis) of cattle, mnlnria 
of m«n and birds, flfld more recently the try- 
pfloosoniatie diftea«e«. Tt i» on!y ^rni.-e (lie rela- 
tkuahip of t)ie flctt Ut plague, of the tick to the 
SootL African tick fever of man, and of other 
m\U* to iipirtllcuiK of nnimalu thnt th^ importnnrn 
of ijiac<::t» in tnuivmitting bacterial diieuea hiu 
hnn r«cogm£edK 

It ia an interpsttng fact that coDtagioi75n«fia U uf^<i bf^m 
voMittitnea aimulot^d in a dl«ca»e which in tmnv- viumii. 



ioitt«i! unly \ty ijititci^. TIiub, for tuaiiy yeara, yd* 
low fcTcr VIA held to be eo contii^lout« that not 
only direct trnnufer from person lo person w»* 
fidiiiilt4<0. InU aUo t]]rougli variouA indJrf^ct ujeflns 
Ae bv foniit^. Typ}]ua fovor hae often been cited 
us ttio mu^t (Mntn>!iotm of nil infrdintit^ yvi mkhI- 
em ftudic^^ pwnt rather rtrongly to on cxdn*iTe 
in^wt trj^mfiniisfifin (p^rhflfw H^au or betlbii^), 
Thf condilione m plaj^if !H.vjn (o be somewltat 
mtirc pomplej. m that botli in^i^rt tranpmi^aion 
(flrufi) [iiul contngioHsness |»ri*vnil. the Inttvr com- 
ing into play in the pneumonic form of the dia- 
€flBe- D&ngtj«, which ejiipflri* like wild flrt^, pos- 
sibly !r transmitted only bv th« bites of certain 

In lorae inetances the rflle of the ioeect ia an ob- 
UiCntp one — i. c, transmission coo occur in no other 
wrtv than bv iU bilo- This ia prt-ominentlv true 
i*i rnn!iTrisi, which, rirtimlly. ie ini^apablp of trnnH- 
ti^ission from i)er*on lo pereon even wlieii iiinlanal 
blood le injecteil into a heikllhy j^ereoa The par- 
Bsib' whcH it h'n.vf* th* body b&'(»me* iufucUvc for 
mnn tigniti only after it liaa completed a semal 
development in the inosiiiito. In aome instance? 
infecliou nmv hw carried fratn pt?r»ou to person 
or atiimal to animnl by tho injection of diReaied 
bWd. vri iindnr jintiirfti rnmlitbtm thf rfJe of the 
inMCt is an obli|:ati.' one (yellow fever sleeping 
alckneu, Boeky Mountain apotted fever). The 
Hea in plagrie trunKmis^ion ia sn example of a 
facu^Intivc rf^le, flincc> a* stated, thifi insect is nftt 
ihe only natural meane b_\ which tho disunaf? H 
convov'pd fr*ini pervin tn pprpon. 

Initortjt ^v^hirh cnrry iiikd Lrnn^init inf^c-tiiin^ nnt- 
urftlly muet hn\t 6ome source ttom vhich they 

aovRCKii op iSiiKci txrisvTiow 


derive the micro-OTjeiiDiemfl. Commonly, tht Lran^- 
mifftion o«?urfl oclv l>etwe*n <1ifTerenl mmTib<*rs of 
lh« mme spctie* : llr Uiped obtniiis tlir vinis from 
oac indivKlau] ant) in^milntc^ it inU> nnothov. In 
*i> tmf itn U krinwn, mpt» alonp oiiffi>r* from veHow 
ffrer, find the lininflQ type of malaria, and he 
roDitituto the only ^uk^ oF infootion for Iho 
moequilcHii ivhltrl atv mncrrnpiJ in tli^* mnintp- 
UDCO of Ihote disenfips. 'ITio ftamo ronHitione ap- 
pwr to pr^pil rpgnrrling piropTssmnfiia in rsltle 
(Teu» itvtT) and in otli^r animals, nnil alwo In 
Ifce South Afri<*an tick Um!T at muD (a fpirzliosi^). 
diMjuk** in V'liich lickfi nrr trnh^iTiItfrr^. Pre- 
tumabiy this ie al^ tni^ of som<? other insect- 
bnm^ di<pA«« ftmcn^ nDimflh, an tlie «pinllOEi4 of 
fovia aad ge^e. 

In eomo other inManccH ihe ruittt^cc of a third 
bod ha* bcto dtmoiutrnW. Mnn U on important 
source of irffdi'>n for tbc Hie* whicJi corn ilecp- 
m^'?!irkt]»*. hnt ihe evidenr« i» ftrr-np Ihat iif>m*> 
of t!iy iialivt? auJmalH uf Afrini iilno harbor the 
tnrpanMomc conoomod and that Uct^ Hica be- 
ciatno infiv^pd from lh<?in n* wdl iic from iiino. In 
Rocky MoiiDtain spotted fc^cv man i* virtually a 
ne^lipibl^ fatlor for th4> inft^etioo of tlit? tickr. 
Thff cinrumstumtM jri{IiL'ali< Uial mw. or nioit- »[»»'- 
ekf of finall, vrild animoU, of dcmoTwtnitcd m#- 
ceplfbiHty, are flie meann of k^epin^ Hie diwaaes 
jLlhi* in thv ikkd, II upjx'iir* Ut \t\ay l>nrk nml 
forth from t»?k to Animal, and it is oftlv oot^a- 
fticDitly thnt an inf^^l^ lick bijoofHeiS attarbpd to 
nun. Flcni |ir(.^hiibK d«'nv(' tin? mirr*i-orj|Eiini*m* 
of plague from rut^* in lar^'C nit^a^uri.-, but expfri- 
tMoitft aiw3 show thut lliov may become infect»?d 
from man. 


ts-pECTioy ,i\D int^vxrry 


Aside from the sourew oi«nticned, the poasihil- 
iiy also eiUt*, in idntion to >oin^ irfrftiuTi*. tJiMl 
the rtruws nr* notirc to t^c insect*, or, rather, 
thflt tJiey are habitufll pnrn^itos in thmn, ju«t u 
tlip i:t>]un baciUiis it A coiistflui iatiabitant of tbe 
inti^tindl traot (-f itmn. Evi^tt in thifi cuc^ how- 

source for the orgnniBms or thnt they arc inhcritMl 
from the prpcoding j^neration of iimwl"- The lit- 
ter, indeed, i* a nitthod of aoquisitioD wLicli hu 
heen &hown to occur in tick*, in relation to the 
T^na fev"er of i'^IIIt-, mii\ tlic South AfricHu titk 
fcrrr, and Kotkv M^'untuin spotted fever of min. 
Tlie pjEgs of inTw^tiH] frmnles (vinlnin the rwpoptJYe 
micro-orgfinisma nnd the larrFt which hatch from 
th<?m an? infortive. 

Till' fnfUini whirl] Piinhlr Hn inB<<'t.-bi^mo dieease 
1o be maintained froiji year to vcnr \ttry a good 
deal in difTerent ca^o^. ChronicStv. in eUher the 
animal or iratrct ho&t, or In htith; inherituncE^ nf 
tlif diecttdc in tlic iusix't* und a rjipid altercation 
ijf ihv inrrrtifin hHwirn l.hp iiiwi'l on the one hand 
ond the animni host on the oth^^r — Uu^e AGtm to 
he the ininorlant eonditions whieb have a hennng 
OIL tnaiutcniuict; in unc? discd^e or amitlier, nnrl all 
of them £8eur( a more or leJ*j conetant eouren for 
th^ fresli iufoclion of the earrj^rg, 

Tejas fever of cattle and other pitoplijMrwtie 
iD/ectionSj mainrin. and sleeping-sickness are 
chronie infeeliot* in both ihe animnl and insect 
UoHts- Enoh 1-1 ict^ na n moTti or l^s prolrneted 
source of infection for tlie other. In addition. 
Te?<fl£ fevtr, and fiom« other piroplaemoeep, are 
heredjtarr infectione in the tiek-ca Triers, nnci in 
this way infeL^tion in rredily kept alive from one 

ifin-h\ MviwTAis rmtiie, 




t^lvk Vrwur. 

9m»a to tlie wxU It u not ye( known whellie^' 
■lecptti^r-eickEcfs ia irli^ritod in tlie Uclee fly. Mo- 
\ATiit if not BO triinnmi1li*(I in the mo5i|uito. 

There may bft varying grade* of chmnicity in juuHi *"' 
both Ihr animal and iiucct bcxtn- Thub South Af- 
rimn tifk frvpr of nmn (n Hpinllfjsifi) in spmi- 
diroi^L'. consiftiii^r of seveial raciirrencea fi>l]o^-er^ 
by rwoveii', and it u probable tliat tlie tiok ma> 
AC<]uinr the? diwa^c fivm thu patient ^urin^ any 
OM of Ibc rccurNn^iy. In the lick, hf>wcTcr. the 
tllH-ntp i« rhmnif nnrl lii^tpriitftrv. 

[n thrsi* cnrr* ^h* mrthofl nf innintenance is 
gImf, fl&d ia tbc proMrtioc of a Jtuflicio&t mimbor 
<rf iiu«rti; the coni^itionft are ffLVorable for a 
thoroQ^U infection of fbe inbfLbttsni^. Thos it b 
tl»at in mtny tmploal distrlou thc?rL- are noc* wlio 
do not fall riciiins to makria joonc^r or lalcr. 

Fn Kocky Monntnin ■jxitlcd tcvcr wc have nn 
oxHjnpIo of n c^onHiticiD tn which tho rli«pni;r \f 
aci^t^ in the various animal ho»t», including mtyn. 
bvt obronic in the curnor, the lick. In ordei th^t 
fn-»h lick* iimj Mcquirr- Uiv tli_-i'«-MP JL ih nw-vwary 
for them to feed on a nu^cptiblc ammut in com 
pany with inf^rtx^J lit^k*, or nhortly follnwinii n 
ff*Hi b\ the latlfr. Since Mvcrni hiitidrcl Inrvo; 
or ryniph« mav be fomid on oig of theso oniTnaU 
at i!uT ManiP Liim% it h n-mlily KfHk brnv thin may 
be accotnfUihcit. ^liiLc certain of ihc rnmlJ am 
malt (grcnnd «i|uirn;i], gronmUhog, rock-i;r^nirrel, 
and pcrhaiin olheT>') an: in hiWniition [\w 
TiriM rtill liven in the ogg*, larva- aoil nymphs; 
and whtn the nnitnaU '*C0TOe out*" in th? Apring 
lYdain of tVnt Womf inf«-tf<l thnJUKb tho bittt 
of the Urvaf or nyniphe anil tlien are in condition 
10 infect fn^h tick;. l[enf-« the db<afi« U kepi 

In Ilk *(]>»Mrta 


/.VWtT/0> ,iXD tM^ItXlTY. 

alive through inherifanf^e in the licit during Ih* 
luuctb^ of wbttrr. flod at other tim« UiraiiKli 
altornatioa from tick lo animtl ind ftntranl to ticlc. 
Mad jiliijrH little or na Mt in itR mnintf-nnntM*, Hiid 
hU occaeionoj infortion through the liok hit« iqqv 
be regarded, in n (leuHe, «« nn iine*w<'nT^«l incident- 

Yello* ft^fi. again, illii-lraU's lite rondit.ion of 
an ucutf,- iDf«ctioi: iii tbe aiiLnml Loat (maiit and 
a rhrnnit* In thp intMwt (^trtfomtfia raJijpvv). 
1-ike Rocky Mornitflin upotW fcvrr> the vini* of 
\ollaw' fevoT li 1 nirif mit1*(i in a herpdilary raaO' 
iit*r lo thi? iK'\i /I'liii ii(iini cjf rtKPHijuilueB (Mar- 
ohoux and Siim^nJ) m come insUuccs at lemt." 
nm^m*. "^'^* oondUioiu in pluffui? are fwt^uliar in that tho 
iliwjwi* nins an ru'iilr nini-Fc in hntfi Uip rtniinnl 
hofts (raU and man) and in the in/icot trans- 
inKter (floa). Rnts do indeed Fiiffer from *"bronic 
plapiR in 4otni* iiiHtancpH, but tbia h not a wpU- 
romi<? oondition, hi^noc it nlTonlH tittk or no nppor- 
tunit.v i**r the infection of n<>as, 

It may be qnwtioned Hhrthcr the pre*cnec of 
plague bacilli in the ^otnAoh nnd inteptin^A of tli« 
flea eoastttnlc* a Irne iiifectJoii, bat it '^et^iriB jontl- 
fiahk to tttko this view of thf: condition, since the 
bacilli apparently proliferate in this localily for a 
few diivs at b^jj^t (Verjhttsl<i), Wrjbitski fomid 
the! flcn& will trnn^mit plu^ic for three dayn after 
Iht-ir infection, the Indian plague eomiin&eion for 
frcim eigbt to twMity-tiiip ilayw depenHing on the 
tetu|>ei'atijre at vblcb ibe Lnspcte had bt-eii krpf — 
ier twenty-one dnyw at rc°'80° F.. for eight dsvf 

0, Tbp nvlrltili robiDlatlnn afm^ ntppoin fn hntp tt^ou itic- 
tMnfol 111 itri^vlnij tKIh htrt^'llTary i taii>Tl4flnTi, iilThou^h t^io 
attvDpl Imil l0tl<<r1 111 ttu' Ziriurln nf Uted. Cnrrol Hud A^jm- 

only fL tir>«lT pBrp(ihtHB<^ Df ^bf EnitFlm. 





at 90" F. Tbo6c findliif^ also c?<>rrefiporK! with the 
bai^tcriolojfjr exuminution of the intestinnT and 
sttomach conUnl*, VergbiUbi's work m n^lation 

to the bpdhtjg and pla^* wajj referred to abov^, 

AlLlimigh phigLce is ;if'iitf" in hnth thn fluiTTiBl 
dii4 insect hoEts. niaint«na[ice is facilitntcd 
through the Jarp« niitnltfre of both hosts wlilch 
arc j>Ti'Knt in pirjgiic CL-atert, Tho ctnclitioiis 
rpn<iT'r |>o«it)!r a moro ot Icm pormanont conroo 
nf fnfprtion fnr th*> flpflH thr**iigh (Tip cnntimipd 
iof^ctioD of fre^Ji rat«. Tlie jio^t^ibility also eitata 
Ihflt the chronic nodular plaf^ue of rnU may bo 
subject to t^xncrriiiktindn. iirix^miiiuiidl by r^nfiti- 
trvmic infwticn. a :*onf1ition which would afford 
ppportnnitr for ihe fiirfhpr infertlnn of fl&aa Tt 
haa recently bwn shown by th* vii>rk of Whetry 
and other* that the California ground-^qoirreU 
have pla^rd a pnrt in Ihr pi^rfiKtr^nce of jjlngue m 
Ihnt mgion, il discovery which mrtv have profound 
epiflrmioTngii' iiofKirtance for the HnUeil Static 

Tnhmtanc? in the iii«cct lina been mentioned aa 
a faolor in the maintenance of Taxaa fever. Af- 
rican ticV f^ver of inan, yellow fevei nnrl Rpjcky 
UcunUin *pottpd f*v*r, Sfhnvdinn also foiind 
Ihat the mosj^tiitocii whifh csirry Tiypanonfljna nOf~ 
twz (the *'hoitcTidinm*' of the etone otti) pass the 
ntioro-or^niemB to the neit generation throu^» 
the e|{ga. In Tciaa feri^r thtri ajifieaT^ Tii"tTiii!ly to 
be the tin* qua non for mnintcnnnre iri view of the 
[Hvniliar habit of thp lick of going ihroiipli its van- 
OBB tiagea of developmrnl on the host in whidi 
tiio Urrjc Rret become attacbecl.^ In order to mak« 

T. Uoat liikB t^BH E^toiiRh (br*^ mellvv ftlji£» Id ttirir 
■fi«r * iittioA at ml, Iftjv * crf«l n&nT •ok* Follftwlnff 


isracTios A-vn lunvsnr. 

thU point d^r, l«t m aecuni« thit the clUoat« is 
not hereiltlary in the tick. Let some nonnal larvn 
beoom« ottochcd to tn infected etMf. Thci tnifflit 
acquire the diBouve fruni this pjiini«]r but (>oliTJ 
plflv no part in the infection oi other*, since t)ir>" 
clo not Bbairlon thii- hofit until they have renrh^ 
|}ip niliilt Filagi' arkjl t1>e femfil^e ar(< prepared to 
lumiiBifx- lav epgj. The Utlt^r tficu drop and lav their egg9. 
and, in luronlnnci' witli unr Essumption. tJii* tarTH^ 
which emerge wouM not have the power of infect- 
ing fni'ther animal*, Tn thU cap* the tirk would 
be a fttotor iii niaJnt+'ijance only in the event that 
infeofpd iadidduala stjonid throtiph accident be- 
come dislodged from one ho^t and aubaixpiently 
become nttftched to n sn3cq>tzb[c animaU Thw 
may oeenr in (ome tnatance^- 

Tlie comlitJons iiie different in the ease of 
aj;othcr pjrop]Q?moaia of caltk. namolw the 
Rhodrfiiiin or Enflt Conttt fcive»r, whioli oeeura fa 
Africa. In tiiis case. a& determined by Lcnnsbtiry 
and by 'I'heilPr, the brood from an infected female 
iii nnl inrcftivp, but Inrvje. whnn fnl nn dispflse^ 
blood, art- infective after reaching the nympha! 
itagL*. and. likewise, when fnfeoted as nymphs the 
adults linvp the pnwer of trnnaniise^ion fRhipi' 
cephnJn^ app/^jifiicTihtuf). Thi? i* known a? atoge- 
to-stflgfr infe^ticn. and ih .important in this in- 
stance, inflfimuch ae the lai'va- and n.^inphB leave 
thfr ho*tt to moll. Following the molt they fre- 

laon bH<nm« Brriioh»d t*> linclB ThfD thi^j liivi^. pi» Uttit i 
quIcDCL-Di ■l4st. iDiJ LmtLov ■ w]i\tv iblfl, apiiFar ah AJegictHl 
D^nnpUi, Thi'to Aim fwd, botfoup ^ukicenl (or d £*i"ial. noA 
nttlnir ^1T n vtit* iltln ir« nnw idnru, vhlc^b nrv dllTi^r- 
MitliiCfid MJHUilIf. Id foOit lDfl1aaci!B. aa Ed the lick ttmufr^ 
altting T*iai fivtr. tolh toolia uccur un the best Moro frfr- 
qouiIlT, Bovvwrt mli*' npoflm Itnv^ riie host to motE. From 
MTvnt ivceka to *«Vfiral uoDitt «rc rft|alrtd far tb« wbat« 

n'ilEtUTASCB OF J7WJ/'L-i»if.itf, 


^oently r««di «iieceptible }t<nU, and tbua keop ths 

another «i>*€ics of tick { Rhi^k^pkiihijt df^olGTO' 
iut), found that her^itary trauBmi^eJon ot 

I^Toplfterooaif of iht dof? prf^nto still Another 
IstcTOfting condition in ro>znrd to inhcritiutoo in 
th* tick, Npilhcr the Unw ror the njmph* of 
an infeoled femnlo ore Mi^ to produce the i^iwniic, 
but nhon thoy reach the adult sta^ th^v becomo 
infrctivp, Tt httR hpen n»i^i)inp<l timt tlip jtenoil 
btftirceii Uk c^< and thi; iiUult j^ta^c is reqiiircfl by 
the micro- or^ianTsni for the completion of ite ees- 
nal ftvolution, th* Inttpr imng n^^Esaarv' before it 
coulii a^iu hirt^iimi^ in fiTUv<v* This tick also l«avei 
its hoet to molt, hent^e the fidult« are able to iiifect 
ntw hoaU. an^ from the latter freth tifrkfi mny 
again becomi! inf«U«!, Tlie iliwaM* h fwqm-ntly 
chrooic in tlic dog aa well as in the tick. Motoa 
fonad that the tick Rkipicepfmib^ burufi, hchavo* 
in a aimilar vftv in the trau=mi»]on of pircpUs- 
moaia of aWp. \u thin InstjLaL'e the tick Kinaiik^ 
w the host for the first molt, but leavp^ it for the 
■icoiid. An infected brood is able to transmit tho 
diieasc onl}' after h r^ach^ the ailult «tage, 

CUri&lo(i1ier6 lias lepitrliid aLiII tuoOier variHtioii 
in the inheritance of firorla^mtiA, in tho case of 
Piroplatma ccnit in India. T]ie titk conoerned in 
thie in&tance was Rhiplt^'^phahis siiit'jniii*'iis, whieh 
leavte its hoal for both mo)t^ The larra? of an 
lnfod«d brood are not virulent, hut bceome bo 
Lirhcn Ihey reach th« nmphal and adult ?tag^3. 

la |B»*M 


7« iSFlX'TiO^ JAi* t)iUUNlTr, 

Rocky Monntain spottM f^v^ notonlir i* JnW- 
ited in the tick, but both larvtt! and Djmpba maj 
aet^ahe th« disoiic l>y feeding; ou bifectod blood 

ATifl trannmit it hv hiling vhpn thpy iVAch thn Jtub- 
sequent stage. Hence both tiereditary infection 
and *taK* 'o Blagc infictbn occtji' id tJiis omo. 

It 14 C|iiegtionHble wliether any dinea^^ can he 
majutainod iu nr intwct indt^Jinitdy tTirou^h inher- 
itanco alone. Moll^rt* found thnt South Afriown 
tirk fevtr roidd l»e currie^I tnUi tbe tbJid ^Dera- 
tion of ti^kH (Orniikodoron imntbata), neither the 
HPTond nor third gGnerntion ft ticks Imviu^ had 
opportuuity to suck diaea^ed blood in the mean- 
tirie. Thtf expcrtrueDt wee not carried beyond thia 
point In relHlioii io Hitcky Muuiibiit) spotli*d 
fever not more than f»0 per t^cnt- of the iafcctcd 
femnles tmnflinit the infecn'cn to iheir otTspriiig, 
hcm-i' iiminknancT; through hiliprifHiict alone i» 
considered ob inipoaeible. 

Ctirtflin con^derBtion? relative to the ooune of 
infrrtinTi in iiisec^ the iomhiitirn ihtIwI wliidi 
may intervene helAvwn the moment of tbeir inocu- 
lation and tlic flppenroncc of infectivity, and, in 
addition^ the duration of tbeir infectivity, are of 
interest and importaiu'e. Tlwee points may be 
di^cuascd briefly nnd only in a general way. 

It in rtrikiDg that di^Ase^ which are trans^ 
[iiJltcd by irisei'ta nppenr to bnvi' little pathtigenic 
inflvitnce on the insecte themselree. The malarial 
plaeniodia pcoetrnto tliG wall of the stomfieh, rouch 
tho body cnvity and eventually the enlivary glands. 
nnd thi«, it wt^nld seeiu. without coTnpTx>iitiaEng 
M^riouely the health of t?ic mosquito. The ^ea 

FKJUODH OF i\rscTiyrTi\ 


harttOTS ID iU alimeDtftry traot fi^r eeT«ra! days 
nr wiMfkii lliL* incrril \irirltMii pUj^uc bacitll, but 
vfT«itiioliy they arc clr^rcd nway. In tlioae iri- 
stflnc«fl in which hereditary Irflnsniiesion occur*, 
<f ill [jirojilHSTEjopiiH, Soutli ATrkiiti ttL-k fever, and 
Uocky Moiintuin npottod fcvpr, the cgg^ may ijon- 
tftm JflTg« namben of tFi« «pocifir micro-orgnninas 
tnd Tct gire me to apparently healthy larvae, 
Kinch lire nblt to jF^aefl throui-h the suci^easive 
tlnp^i luUi tin* a\\u\i f«rm, *Lill nrtjimin^ th^' viru- 
lent micTo-or^nninmi; m their orgnns nnd oella, U 
is probably by virtue of this bland rdationiiliip 
that iuiiwt)! arr Mv lo %ure an Ihrt t-nrTi<tr!i of 
infection, if tho lottor were more vJmlent for 
the infieft bcwts it la fnir to iiiunime thnt their 
dcAth in \%ri[c numbers would mirjitnixc their role 
ifi iQDCuLatorfi of ether nnimal^. 

In thp eau? of the fl«i mid plague, tlie insect 
if inffctivc immediately or toon after it htm in- 
gaar^ blood, but the period of mferiivUy is Iim- 
ilcil to a tw ikyji (Vi?rjbii*lvi) or at the iiiuat a 
few vocka (the Indian INa^c Comnii$aion]. This 
hn4 b<«ti referred t> nbciT<> aK ooutB infection of 
the jnwvt, Min^huiiJutl ImiiHmUftBion h a term 
Trhich hnii boea itced to pi^ify llio jmtv inf>ehan- 
ieal eonveyaiiee of inicrcKjrgflnisTnK by iin iri*pH. 
from a diMUHcd to o healthy animal, llie rule of 
IWfl in carrying plague nmy be Aimply a me- 

initxl one, partieubujy wh^n it trfltiHfk'i's tlie 
di^a6« iiDinedJately aftt^r ite infeclion, But, ina^' 
mtic!h a« proHr(*rntJou cf ihv bncUluit m^iTm* to 
occur in the flea* abd <iDc« hi» infoctivtty may IsH 
for three weeks or more, proliferation may be rc- 
iponidblo for th^ InUr Infretivily tn thiH ei'ont 
the trau»mI»aiorL deprjids on biuIof;icaT as well aa 



t^'FECTJo^■ AXD lUMvyrrr, 


."^ rti*i'ii*aicfll factors. TraDemiKdi>ii of Uiie type 
pfubrtbly (Icmatid* u hi;(^| itegree of vimlenfe nnd 
:riftclivit.v <ni tlir purt of the micro-orgiaismF. 
HLves^itiitinq: the irtroriuction only of v^yy fimall 
aiirjliei's, Oiii* of IIih ('otic^Itision!* of Verjljitoki i* 
timt "animals ctrnlj nol be inf^rifd by t.he l»ik» of 
flpfls nnd bugs which had h<^n irfocted by AOimflla 
wboflc own mfaetion liad beeu ocL-aeioned bv a mil* 
lure of small virulence, nolttUhstandirg the fact 
that tlt(* iritiectii ifiRv bv founri to rontnin Abundant 
pliiyuc microbes.''" 

Another condition w roprcwutod in Rocky 
Votintflln fipotle<l fever, in which the inflocl^ aro 
infective not only immedifitch' or ■oon nfter suck- 
ing dmcWL^d blood, but aleo for an indefmite sub- 
sw^iient period. Tn tbis iri?lsrce the tick nnfW- 
goea genemhjicd infection, as prerioufily men- 
tioned. It tit pOHHihle that the cofivi^yaDco wbioh 
tAlcpa place imiTL^d lately flfter infection is of ihft 
rnecJmnicnl ty[>r-, but thin i-nnnoh be triie of thr 
UUr tranemiiflions. nor of thoae by the members 
of the following poncration. In the ktter vr& have 
to do with biolni^cftl trnnsmi'^sion, wbinh tn tliose 
two rfiies depends on prolif^atioo of the micro- 
or^nnidme and a general invasion of th? tis3\)08 of 
th<i iner^ts. Tbf t**rm '*biologkfll trflnsnii^?ion" 
svne oj'iginally applied lit llioec eii?es in wiiirh the 
micro-oreani&ms tpr'>t<*zo*^) nndergo a compli- 
eatcd (Dxunl cycle of development in the insoot, ft* 
la rialarJH, but the principle reniaiiiH ibe Hnmf 
witii the bnctcrial diaeaaesj aJthongli the method 
of prciliftratioD is a eimple one^ eonsiatin^ vnvToiy 
of iltoion. 

10. jQur flrBl«B». I1HJS, viii, SOB. 

I^CV§LiTtO\ i\ iSliKCrS. 


Wb«n t]i« rnosquitoQd of maUm and ydlnw 
fvfisT Slid disensnil blood a do^nit« incubation 
period must elapse boforo tlicy nrs abli? to convey 
infection to otlier mHiviflnals by tlirrr bi(j^«, Fnl- 
lowing llie ingtetion of majArial blood by thi? ra*>9- 
quito (Tarioua £pcc&<s of An&ph^tex), the pftranit^ 
undergoes a Miunl typi* of prnlifrnitian m tlic in- 
Beofa ftomacb, the product of which, tho ^ickk- 
itbaped bodw* reacli the salivary glands only affer 
dgbt or ten <laya- Tticse are tlin pathogenic forms 
of the pflrjuiU whicli ara inocLiUCed into ninn b^ 
the mosquito. Ir tW intermaliat? 'rlage* of thi* 
cycle tb(5 paraeit^ i* not infective. Tb<j Tin>'^<|U]to 
(Stf^omi/ia) whiob IrnntnitU >*illow fever U not 
mfectm uniil ot k-xwt tvekt i]A,vg after it bas 
tncked di^ea^ed bIcKid. And it cow appears also 
that a ■imilnr innihnlion period n^ciini in tbr 
iMtw fly in ita rGIe as t1i^ carrier of sleGping-aick- 
Bctt. After tho ia^ects are onoe infected, however, 
ihaj rontimin Tiriilnnt for a long time, TTrntr a 
pnmsiv Tion-inieclivc atoge is succeeded by ft pro- 
lOOffftd mfeetivc^ 4ta^i^ In thi« type of triLniTTdflaion. 

Od Ui« baais of tbc i^"iidition« in TitalnrU tbt* 
tomptation ha& been a ^troDg one to conelude that 
a pHmar^ non-Enfeetlve 4ta^;e — Jneiibafion period 
-^in tlie insert fairicr i* indicntivc of a »riTial 
cycle in tho ^e**lopment of tho p«raj*itG; hence 
■bo of tilt* prr>to3;o«i] cl^arjitfrr of the jiara^iti?. 
Thuf it in anticip^tcfl in mnny quartcrEi thnt the 
micro-orpinisra of yellow fov^r^ at prenffnt un* 
knmrii> will prove to he a protozoaiL. because of 
tht incnbation period in tho moM^uito. nicntionod 
abOT^. Koty, bnwpvpr, bna rrry npMy pnint^il mif 
that ao i&cirba^on period in tlie inject might vi^ll 
occur in tho i^rnv of ti }>acteriAl dif^oae ne <r«-l) an 



i\Ff!frrmx A\D iMtvnyiTY. 

in A pi'OtoEoon.'^ Given a fflu in vhich tTie di^ 
I'ABe id oaiued by a bacterium rather than a proto- 
£uou> we inn.^t auuiiit, i\nU that thr iiiri^ctidn in 
tito inflect ifi limits to it* aiimcntnn' tract; or, 
'H?ond, ibst ti generali/e*! infection of the mirfflr 
lakes plutc with n loadialum at tht micrO'organ- 
iem£ in itK »ntivary glands. In thir firat inatanee 
n 1nr|f<^ proportion of tli# organisms ingp*W witli 
lh« uiforrlcd l>lood rencli tlie j'tomflcli and into- 
tiriw, w}n2rt^s it ia probable Uint n rclativoly *mall 
number rcmaiti in the proboscis. Wlieu the ioHeL-t 
feeds ot once, or soon, on another {heaJthv) ani- 
n^fll the tiiiniher cf iiiEeru-organisnifi injc-t-tt'd from 
i\w prol>iMci3 mny he insnflicicnt to infect the new 
hfWfl, Som« (lays might be r«<]iiired for prolifera- 
titiii to re^uit in an infective quantity, uither in 
111? probo«ci€, storoach, intcflince^ or by conUguona 
riti^nxion, in the salivnTy dncta ntid glande. At 
the time of inoeulatif>n the micro-orgnnisuis might 
Blmply be washed frcm the prohoB<?i? into the cutis 
by rnpnns of the snlivnry Kepreliori, nr Hirectly in 
Ihe latter or alter a certain amount ot regiirgita- 
H lloti from tht; ^rtoznach had talcen place into the 

B prolinKf^ct. 

I In the feeofid caw, in which Ihe insect under- 

■ j?OM ft gei^emliTied inf<vtion, the prmmry uoo-in- 

I feetive period (incubation period) may well rep- 

^^K Tdttmi tlie time required for thij? gcncrnl invneioQ. 

^^H with the ci>n!4eqiient loeGli^atiun cf the bacteria 

^^H in the aalivarir^ glauda. We have a rery good 

^^^1 ann^logv iQ tyjibf^id fever in man^ in which a rery 

^^^P delinrU iucubatiou ponod pror^des generalized 

^F infiTc^tiOD. 


11. n» Rbl* of Pml«ios in I'tirtnTno* ; !*»& ot lUv nOi. 

MVDK fJJ^ liifKitVT rK4ys\tI/tiiltt\. 



Hcncc it ivcm» pOHribIc thdt erron mnj rR«itlt 
ia •eBuninp that a pruDary nou-infoctivc period 
in Um Inaect poinU» in an obligate mamiBr. to the 
pTotcscoD naUirt of a pnnubtc, 

St> far wo bare ooDsiderod three tjpee of imnE- Jrp^' 
inimimi bj ijiMV'b; iJir [ii'Ht, in wliicTi the inetH^t ii^ 
isfcctire imiDcdifttoly or sood after in^ttng di^ 
<«fltd blood but not for a prolonged period |t1ie 
fl«a in plAf^i*^) ■ t^i^ Mrconil,. lu uhich Uie carrier 
is inf^ivo almopt immcttijitcly atid for a proloti^ctl 
period lat*T (liirlcs in Rocky Mountain *pntW 
fever); third, iu which a humitefiA incubation 
p«Hor1 Id fotlouoil bv a proloa^ed virulent period 
(mnlnrin ami jpHi>w fcvrj). 

A fourili pcsfiiltility, which ia perhipa noi yet 
IhoTOughly cctiibliihcdf U that of aa immediate 
i&Jective period, followed bj a noD^iafectiver fol- 
h>ire<l afi^ain bv an tnfoctivc. The conditions ae a^- 
cvrtaiiiul wj far inJieatc ihal Uii* may he the c»ase 
in the traaamiMion ci trypfinonoDnca by t^eUc fliee. 
Until lately it woe the experience that the fliea 
eoiikl (xiinti rmfaiJi onlj fur ijii« or two days 
after Ibcir fcH on infected blood. Lately, how- 
♦T#», Kleine" han fo^ind that ufi incubation period 
4>{ about IttfTiiti datp, or a lltih- h^ ui^cut^ iit the 
Hf, and from Ihcii on, c^ce np t« cigbty-three 
days (Taiite), it in Mb lo trBinmit infection, 
Tliia work lias l^etu don*; with tlie fiiesn Glonsina 
mcnitang nnd 0. patpr^in, in oonnection tvith the 
trjpanoiome« of nagana (7\ hrurM), and sleeping 
Mckiwu (T. gapihKnsr), The rcsulU hiive been 
corroborated hy Bnirr^ 'Fh^ finit stage of infec- 
tivJty of the flie^ then reui^iiie fur i-A)>UiititJon. 



IX DPOtMtir onvd WebnwIiV.. M«rirli la. War 3T turn Juip 
»2, ltO»- 



at Inivecl 

It ifl {]OMil>Te tSmi tlii% ift purvljr a tiiM^aikicHl tntn*- 
miMioD. In rnftEj of the cxpcmncnts nithcr lari^ 
nuinb«rfi of llJM hav9 bMn mi^ on * single anTTunl, 

and b litis (^ase «Q iofecuvt quantilj of tit- j^ra- 
sitec mi^ht well be iairoduccd mechanically, n-hcrc- 
nf a. single i\y might htt mh\t^ to pnxliirif inf«r1i<in 
only aft«r the paruite had m^tipli^ m its tia- 
aue^ and, p<!r]iapft» had readied t)ie aalirarj.' p;!andft. 
It is wrl! knrjwn that nu intfrninHotj' "iiiwH 
»tnjrc" of the trypnnwoire U noi required for mfcc- 
livity^ Bs Appears tn be the ca&e vlth malaria, 
Trrpanosoniatjc difteaart may he (tarried din^K 
fi-om one aniniit] to another bj tho injoction of 
bbod for aiL indefinite period. A sexual rtage of 
the trypnnoflome haa not yet been shown to oocur 
In the iu4ee fly. 

A unique type of inaw^t traii»iintD^un waa de- 
scribed recently hy Millrr" in Die cn« of a di»- 
ease of rats whii*h it oniiB^ri by a protozoan organ- 
ism, Ilepatotoort ptrniciosum , a tii^w g?mun 41 wdl 
aa a new %pecim. T)w Iranaimtter iff a mjtc, 
I,rlaj>n rrtiuinintis. Tip luiter deriT^s fU infertion 
bv sucking tJie blood of diseased rat*, in which tlie 
iniCTO'Crf-anifiTOK, at a parlioular Rlage of their 
ilrvrTopnicnt> ocnir within large inoDoniide»r leu- 
c-ocyb^e, A »eiiia1 phase of the parasite lakea place 
In tlie ftlomarh of the mite, forming an oolcinet, 
Thft letter pcnetmlcn the stomach nall^ reache! the 
body cavity of the mite, and beconios encysted 
(oocyet Atage)- Within the eyat the parasite siih- 
divide* to form a number of sporohlasts, each of 
^hith eventually contains from fourteen to twenty 
^poroataite*, Millar readily pmrlticed th^ difiense 

U, Itiill. V(k 4A, HFrl'qk Ijiboritorr V B, Publlt HHllh 
nna MuId«H«i|i1uI aeiYkr, Vv^htnaios. D, c, 


ia iJUiDj raU br ftt^diiif: Elii^m bn-ad wtildi had 
been miicd vith cnuhcd itifc^cH mite*. Tlie in- 
t4«tkrui1 juiocd of the rat br«ak up th^ cporocyrt. 
mill hrt friw llii' uporomU-j, wlndi as "vermicuW 
pCDCtfltc to the vein? and Ivrnphntics and reaoii 
t)ie HWT, whore thev undergo an a^evnnl prolifera- 
tion witliin \ircT ccll^. From tli^^ the ^ouag 
ni«-fi>3i)ilc« tiTo libcrntrd nnd rciK^h the genial ctr- 
ruTatinitn again ms tfniiii'ule^ It i» the ]a*t i^tjige 
vhfch J« taken n^ afrmh by the milet^. Although 
Chit «porocyct« mar occur in tho »ilivan- gUnde of 
the mite as tvdl &» in other part« of the bixly> Mil- 
ler found no reaaoD to bdiov^* that i\\<^ parasite \a 
ino^latixl Into th« rat Ijv Ihn btt^' of tbf* mit*. 
The latter feeds only at ni^lit* Icavic^ the hoft 
ilk tlie iJAV, and at a inbe^qacDt K'cd may well 
micti a hmlUiy mt^ wliii<]i in him be<]i»m€s in- 
Jictcil by eating a ^efficient niimhcr <'f the niitw. 

Dler repro^U€«d the infeolion also by thie "nat- 
onil" mcthtK!. CtW moilu of infi?etiur, nrtilidal 
in oliarnctcrT prorcU to be nn!iurcCJi?fTil. 

That uucoctK may huvo n rvlnti'>n to tli« main- 
tenaoce and ett)>DBirin nf f^omt- fliAi?ai^8 t'airsei] by 
ntUtJcdlular paroaiben ia Ulualrutt^ by the trop- 
Iral ami vublropicnl di«raiL(^ of filarinich, of which 
dtphantiasif 1% one of the most proaouiiced clin- 
imJ fymptome. Ttio larval wormu often oxiet in 
lar^ iiuTnbeni iii lln; hhjTxI of inn", partic-ulwrly 
at niffht W'httx ceHflin iro&quitoca tuck infected 
blood at thU time od€ or mon! of tho vorraft is 
ingadvO. uiider^Ti fartlier iTevelopineiii, ind PTPiitn* 
allj Sere throucb the stonincli wnlJ nnfl reach the 
brmM miiwb* nf the innprt. The ei:art mannot 
ifi which the jwraBJlL'^ arc rrinocciUtird into mail 
ia nnlroowD, It Has bup|km{.-<j hy Man^on that 


Trh»a salaalo ■ - 

mtny of tbo female modquitoe^ die in i}it water 
aftor timy hiv« laid their egpa and tliAt tht wat^r 

nw) of fiich wat^Tf lyeulto in the infection of m>ii 
throng liU inti.^9tina1 tract Suspicion fal]« on 
oCTcral Jpwio" of mo»qTiitoc#: Culr^r pipUrtf, C. 
citiam, C. fcii^ant; An^fphel^i cesiaJU, A, r^m, 
A. maculipennU. 

A nnnibtr of worm^ which are para»itic in one 
animal or an^itht^r art Jfrivf.^ from injects, the 
intt^T uprvinK us ho»l* fcir thr liirvnl ntngw. Infpc- 
tion of the di^ef^tive ranal on^inatee after eating 
tlie mfieetH (Sm Nnttall. Hvffifniidie RimdiieWu 

«i»*<t««iir i4 There ii a certain At^n^* of specificity in the 
trail Bin iHijon of a di^ense by an inifoeL but Ihif i? 
by no mean? nbftclute. ]u yellow fever it appears 
to bo verv *fronp, inafimiich m only one epeeie? of 
moHfjHifo Jipfcnre lo he ('Hpahh' of fnrryinjj the 
dijcope (Strijomyia fiudnia). An opposite es- 
trcme i^ found in (he oaee of malaria, in vhjeh at 
leaBt Jwcnlv-rtve difTereLi sfM-i-iw* of AnapJtrlrx 
hare beeo shown to be capable of cither natural or 
experimental transmiflHioa.** Seveial ^pwie* of 
ticks lire nh\e t<i carry Tcmih fpvcr niiil probnhlr 
other piropUffmoece of cottle. At Icflet two ape- 
oies of tk^ks carry Rocky Mountain spoiled fffvcr 
t'Der/'itiCfntor vrTiusius. Bonk% and D. niodesfnn, 
Barhf). Two ape.^ica of tactFc rtiea iiiay carry the 
paraaitefl of either nagana or dleeping^t^ic-ktii'tis. 
The carrying power, however, is usually limits 
to different speciea nn^er n romn>on genus. As far 
aa observationB have gone i>iily Anophelrs carry 

14 iruR*: Kan* taa iranwrnanfi'i Handbiif^b fl. pifh- 



malaria, only Qlassina flieB appear to trausintt na- 
gana and sleeping aickneaSj and only Dermacentor 
ticka cany Kocky Mountain spotted fever. An 
esceptiou ie found to this in the case of a spiril- 
losia of fovls in South America. Naturally this 
disease is transmitted by a species of tick^ Argas 
miniatm, hut experimentally it may also be trans- 
mitted by Omithodortts moubata. The latter, in 
addition to transmitting the disease just men- 
tioned, may also carry the European relapeing 
fever, and is habitually concerned in the convey- 
ance of the South African tick fever of man. 

CHAin'Kli VIJ, 

1-14 1 hO- 

SrEClAL ^1 \n i::. -tv ISWZGTIOS. 

T1i« word paih^ffmicity, in iU relatioD to infcc 
tion, refers to ih* power nf an organiCTn to product 
disease, aud ofteu to the ciiaructcr of the changes 
which it ciiu«cik Viruhncc iu u3l oxcontiol reepeoU 
t» Hjiion^moiL^ wtth pethogcniciLy, Inii U u»ed 
more commoDiv in describing the degrcv of palli- 
ogenlc povor «'h!c-h a miero-organi^tii po««utitf. 
Thu« virulent an<i arirulcnt (or nou- virulent) 
drains of the cholera vibrio or dipJithtria Lacillut 
lilt sijHjki'a of. 
TsKiptir- To-xitUy refers to the poiaonouB properlic* of a 
microW or its aeeretions. As a property il m no! 
nrrrHKnnly JifAd'-intpcl viUi (lie living inK^ro-prpm- 
isiii«. The qucfltion '\& &ttll diKiLE^ed ae to whether 
toxicity and viruleut-o arc coexl«nsi\c. ev&n if thej- 
are net iilcmticti properti'.'s- Uiii^uublcdlv. toxicity 
ia one of the factor* on which vimlencc depends, 
and, from the «tandpoin1 of the niicro-f^rganipni, It 
mn> hv t)ic s^Ic property. Some orgaTii*me of littl* 
or no pnthoponic or infoctive jw«'cr ncvrrthcloat 
po66e84 a pnitnplaRm vhich h more or le«a poison- 
one, fl» certain aBj^ergilli, j)enicillin or liarinti^ 

lufvi'iit-ity^ or iiifectiotieD«&6, reliiLea tu Iht 
power of A micio-or^anifin to maintain itdclf and 
to mtiltiph in n living hod. On? which is ablt* tn 









obtain A fouUiuld fliiil 10 jftxHliice iliseam*. f-ven 
tt^ui ft vcrr minute qunnttty hoi been int rod nerd ; 
or onp «'hic:>i, nfUi introdm-tiorj, tc abfo to prolifcr- 
ile lo en enunuous d^git^ m u particular liost is 
•aid to be very infective, or infi^otiouE, for tlib bvet- 

IfLru'livitj' IK Mol tynciTi^vmoUE, iinr rs it ii(?tf!&- 
unly coexteiuivc, with tituIchcc or patho^enicitjr* 
Thtii Try^tifKosomQ Uitisi for the rat, ihe ma- 
Uriul parnKit» fnr tlir moEtqtnlo, ntirl the virui^ tif 
Hocky Mountun spotted fever for tlic ticlc nrc 
highl/ infective, hnt have n xery Ion gnid<! ot path- 
ogeoieitj for that; lioatt; T]w hptc^y bncilluA, tfie 
fpirocht^ of Eyphilti:, and the tubc^rHc bndllus 
luive iDaHcc<] inffclivity for m>in, but 1l)«ir vini- 
Itnce. aa indicated by t!w aJov progrM»iT« character 
of tbo discfltea, may be conaidorfid am mod«rHt4, 
although tUe Imal frvrrt inny be tnij^ic eooLi^h. On 
the otbcr hand, cerloin orj>:ani»Tiis poea^sfl crctit 
mf*cti»ily and jirwK virtili'rm* stt Ihp nflm? Hm<>, 
a« plflgoe^ ant^ni:t and the gluiidt-r* banlli (acute 
Sjandciv) for oiati, end the tn-]inno:icmc« of «Icc|v 
iDgaickMis, nagarta and douhnc fui- u-hito mice. 

TTie irirutence of aome niifro-orgniiflirfr is often 
tpedalixM with regard to parhcntoi apccics of aci- 
vala, Thufc nifjulff, warlct f«v«r und Iftpr-twy lu^m 
to atiack riian odIy, and do aDiinat eon be infected 
with their viruic«. StimllpoK ami gyphilia arc \ee> 
tfpecialiu^. ^matlpcix vnu \w mni^LiluLvd inln the 
03t aad to n oerUin degree into ibe rabbit, and si-ph- 
ilis inU monkevfi^ and pcrbopa also into the rabbit* 
allliotigh tin* latU-r mu)' luit yet be deriiiilrlv di-ler- 
nunod. HaJarin and yril'>w fever mfcct only man 
ind Ihe mosqnitcefl wbii^h onrry the^ dUeaseH. 
Uany other pathogenic 0f;ijuii!iin5 are in conirait to 
tboBo mentioned, in thai tbey arc Able to enu^ 

|t»n III 


/^JwrrroA' asd iumumtv. 

di«0a»e in wide rang* of sninialt^ Snoh microbw 
Rfe ihv pjogeDit^ cooci, tlie Lacitli of tiiberculoaCi, 
giaiider*, t.viJJioid fever, cholera, paratyphoid fcTcr, 
tctaniiM, dipbthoriiiT plngiir, c^riHtn of the tr\^iiO' 
»rimi!f, and iiiou^v ot]ii>r«. There mv v\\>\v^ vi 
iiumuQilv. howovt-r, even to Xh^ac mif-ro or^flommf 
of mtliT-r j^hiK^nil virijlL*rin.% KUt-h n* Ihnt nf th* «lli- 
Kntor And the fowl to ictiinu4, and of the nil I0 

Tn rrtnliRGt to (h« 9ianiple« m^otioned fibovo, 
Are the tiou^patliogcnic paraBitcA, vhich expfin- 
mentntion Imn thown to have no, or iiutigniliciint 
vinilnit^p fcir anv iinlmal whateoever H. a^uhtU'j^ 
fljid ij. mtgaUn^riitm arc cited 06 reprcaoutinf^ tmch 
organisnii. Tlie fomiaif, liowever, ii not tb»olut#l>- 
B-ithont pnthop?i>ic powcr.aiiicc it haa been ob««rTed 
Its tlic c-aua« of psQophtiialiniiie in a number of 
caam, and hy previously lowtrtiLg Intrji peritoneal 
rcsintnncc (iiy ihe injoction of ^'nggnssins"} Weil 
cflii*?d fatal peritonitis in giiineA-pijfs with this 
organ j urn. 

StAudinj: somewhat abu>e thew more or Iqm 
hAnnleBB microbes irt pntho^onic power arc the bo- 
oal1«d add-fant grisn bacilli aiid ^irTiilai' organisiua. 
vhich are able to produce on]^' alight local chao^ 
in aniniaK and whidi arc 90on dttftroycd bj the 
nntitinrtprial a^pnrips (if Hip hn*I. 

Vinilence » a variable factor even with regard 
to dillerenl Btraijna of a giveo micro-organiem. 
Dfphthoria hadlH nultivaled from rjirfou« caa«a 
allow a rather wide range of virulence, find siiniiar 
obBeivfltioua haw bec'U niado with regard to tvphoid 
hftdfli, slrMptoi-m-i.-L. ptnmMiororei, tuhert^Ii? I)«t illi, 
plague bacilli and othor or^ni^ms. With few <tx- 
ceptioDi. pathogenir micro^organiamn tend to Inue 

PA88AGS rUltUV*lH AyiMlh^. 



Wdtocc vhcn thcjr art ciiltivntci for aD>' Jcngtij 
of lime on th^ orrlinun; ciiltare m^diJi. 

A comrmm dj^vice for ttie mftintesaitce or locreAat: 
of T>rulcDC« is iHat of piie^agt? through EOitic ^t- 
nlflr nriiniMl- Tlip pnx^L'sa cunsiste ckf Mie inociiTu- 
tioti of tiie animal viih a pure culture, (r4^rtiiittiii£[ 
th* infection lo nin ita courio or to pro*?eed for a 
Qiunber i)f ^Ajr», uod nt Ihra Lrii^f reccveiin^ the 
nneffO-orjE&ninn on culture mcdiA from the tissue? 
fif th^ ftnimftl. Goujt and MetdinikolT modilie(5 this 
Ccchnic by ptacinn a cultun: of the orgjiuiam in a 
tcttkd collodion (oc, uhicb is th-'^a imbedded in iha 
pfTitoneal cavitj' of a tiria^ animaL Aff^i a But^- 
citDt liTj^tL of time the 5jlo le removed and the 
pnM«i« rvpcntod- By re^ieoting th^ [>iu»a;>4- at stiit- 
ibk iutci^alfl Tiruleoce maj tre LiaiataJiied at a 
rttHer conataot lii^h point (cho3«re vibrio, etn-ptft- 
00^. ftc-J. All pfr<*f^tivtf nubwtiluti* fur piivHiig<' \% 
Kuctiniet found io tlic i:Ft of o culture mcdiLim» 
vliicb in iu constitution afpro^inisles that of ihe 
tionm of nu nmina]. Thus llir vinilc^ni^e uf jiui-u- 
nocccci and 0tTq>tococci k rdnined b>' cultivation 
on blood SfzAr cir in rabbit or human Acrum or in 
■icitir lluid, 

Amniitl piunaiTc iDCTeaeeit virulaice in tl;e moat 
marked manner for (lie flpacieg of nnimsi] wliich i^ 
nwl in tIli* evjwrimrnlT iiltbnu^h inme ircreaee U 
Uftiallj nianifcitccl lu^nrd other susceptible spi^aie*. 
la ft number of ^nslanccfl paaeage through one ani- 
mfti r«ciilt« ID decr«tM cf virul^c^ for nun 
<p«clt* imcl #in infTciiw* fir linolhrT- Tliu* P/mtftiir 
fottod that pfl»acc of tlic rirut of wwinc ct^Jiipclao 
{S€hw^\ntrf>iUt^f) through pigoons increaied 
Ttmlenci^ for tliv^ frwine, but it v'a» decrcaMd for 
t)ii« ftnim«l «hen panicd from rvbbit to mbbil. 

r ■■■>■:«. 


lyFFcrmy ako i.^tti;yiTi\ 

The vim* of hydroplkubia, wh«n poxee^ throu^ 
•several cont^K-ulive rnlibiU. un^] lliat uf 4mall|io)L 
vhtm pflSKd through ihc calf, ]qh in rirulcncc for 

Tlie incrirattf of vinilence wbicli results fr<>m 
pnsMgc Ii4* IwTcn cApEoincd l>y Bssiimirg ihflt all 
the weaker and Jrte vimlefflit individnaU of tli* 
eiiltiijv are killeil b_v the ^nim and ]tMcoryi^6 of 
the nnimnU IcarjD^ the more rceUlant and mor« 
vinilfnt- Thitf process of tdociion i* prububly un 
impoi'tatit rui-tur in the cbaage, bat it would hardly 
explain tlic increase whicli oceura when an OTfitmsm 
it, grown on bontiH] noriim. 11 «tf[*ni« probpiblc. ii« 
^nggefted by Ei^cnbtrr^ ond others, that aa a conAe- 
qii«DC<.' ot ro^idtiDc^o in the body of the animal t^e 
{-iilliirr bL>t'Dnit'» iiriTiiuni/t*;l dj^^iiiiAt. ihv. autibar- 
iGTit] factors (boctericidal amboircptom and opson- 
ins) of the host, vhich wonUl naturally render the 
organiBm a more dangin^JUH orif* foi iulMir^juml 
iinimalfl into whToh it niny be injodcd. It in flven 
possible. a« 8ugge*ted by Welch and olheni, thai 
certain elements in the body iluida may nttmulate 
the micro-nr^^HniFme to a more abundant focrntion 
of toxijiH jirid oilier ^i»b8tanceit (ambix'^'plors) , and 
Ihnt the mrrraacd virulence t^ouwd by pasaa^ may 
d^p^nd on the rvtontJon of this power after Uaving 
tli^ tii^3ue» o[ the host- 
It if probable that all or^ani^m^ whkiL arc able 
to livv for a shorter or longer time within the tl^ 
Klicff of fin animal enu^ nnatomit^ changes and 
flbnormal 5yriptoin& sooner or later. ThiSn of r^onr^c, 
does not apply to those which live hnhitiifllly on the 
ciJtaneous or mucoup ^urfare^ Those which live 
on tbo skin do not rtiueh ttie intEinor becauee of 
meehanical obstacles, and re^uarding thow whidi 


tM^di't: Oy UttltOOifOAMHitS. 113 

{lumt the iQUMaa surfai?i^ constantly, it viuiilil 
eeem that an adaptntion has taltm p\a.ce . betn-cco 
mdi KnTitKUK and the raicro-orgftuidir^^ so thHt th^ 
llUer, althou^L oftcu patlitr^emt, are iii^l able to 
■Mfcdetfpcr tio^uus. The ku&t Imrmfcil infvction 
Vmich cne cmiid rontwivt- would tie ont» in whidi 
tbe micro-o^anifiiii di&tijtb«^ tUv ho»t id no vay, 
txoopt in >o f ftT aa it ii^ed a certain amount of its 
»ibiitjinre for nutriliaii. TJiis uoitld b(: ii time of 
Uipkk compantiTQly haiTaicse, panuitism^ whicli 
JD man, U beet illuetratod by tliQ ori^^BuiB nliich 
JiTc liAbiliulJy on the mucauj^ siirfuccs. 

It is poMibTc tliDt harmlc^ tissue inva^iou tindf 
namplw in f-atciQ of the insect^ nlthdu^li this innv 
not be lualuUlntfd positively. The ajjjjaieuL liann- 
Jonctt ol tbc urKHiii&iiia of nialaria, yoUcw fever. 
South Afrintn lif-k frvr-rNinl Hr>rkv M on nlni ii tt pot- 
ted fever for tiic in^ecta nliich harbor tbeni, wo« 
ujcntioned in the ptr<*C'*ding cbapttr. Curtain infeo- 
tionn do, imlriHJ, nin n vrr^- chrcimc ririrl birnij^i 
coorec, ae the ordinary trypanosomiaBis of rats, bni 
tbey au^ not without diBf^)TerabU. or ev^n falal^ 
el!ix-t^ pvmtn*iHy, 

Tbc quantity or clo^n^e of inicro-orgiiQiBm^ re- 
quired for infection depends on tbeir viruIeDc* 
and Ul*" detpcNT of their pjiruflilic potfec (infet^Lir- 
itr) ; tbif vancg with ditTerent species and also 
with diffvrfnt strains of t}^e Pflme orpni^TU. The 
antbiasi baciUm i» veiy inf^ctivt- and may reach a 
hi^ d«gTM of virulvnf>?, mo that a fingk orgtmitm 
bwn knonn to prmtiitv fatiil diueji^e in eTperi- 
ta] animalt. Extremely lubutf^ quantitica of 
fOQto of the more vjnilont trypAnoNom«G are 
wqnired. 'J*he tubercle hiicillus, even wlien most 
rirul^t. i« bardly to infcctirc; it i» Maid that t'tzht 


'J 4 


.%0tl*ii Altai 

ma^ prtxluce inf<H:ttoii when gxrtn intrnptnto' 
uonlly into tbo iniiiitf«-pi^i ond t^ccnly to tJiiTti- 
when inlo the lablrit (M'vMokowic^). Mnny bun- 
liredii of the moat finileiit tbolcra vibrio* nnd 
hpiioij budUi arr wquirod lo pr<Hltio<> fiital infec- 
tion in llio g\iiaea-pig. In L^ontrrtBt tti the cooiii- 
tionfi mentioned arc varioua aaprophytic organism* 
M-iiif*h, r*;jafiili*fc of tJn? cjnuntitv irtrcidui^ii. Htlior 
do not prodncc infection tti alln or *Jo po onlv after 
tii<? ro^i&tance '>f the animal hoa b^n ]owar«d Arti' 

Among UiOAc -who are c^qually expo«ci] ro infec- 
tion m an epitlomic of typhoid fevor, tlic escape of 
rnnny pHjlmhly in ituo ic thn iiigpsHor of q rnnflll 
i)uantit^ of buL^iiU wljidi la inatillicietit iv pioOitLV 
dmwifcc, Iiidivwiuul ruticeplibllityr "nd tcmpcran' 
low j'lisinUnrr, »i-f' otiipr fut-triTs 

(^) Ttfpcs of Infection. 

There arc «id« vBrSnticms in the- physical rela- 
tiozuhips which difFfrcnt pathogenic micro-organ^ 
i«ms boM to tho tluves of the body. TIilk hae 
nlmuly b^'ii hiij^>^phleii iii tlie disciisaian cf infec- 
tion atria, in which it was ^hown that certain 
organism* h«v& a specific preference for point* of 
prjimirj iiivafioii. 

This tendency of a specific rclatioofiinp to pm"- 
tici^lur tieauua u kept up in many inatance^ nft^r 
the inirrt>I"y* hiivn rt'acht'd tlir inti^iitr at the bod). 

TUo niftlJiDal plasmodirt enter and doutrov the 
cryihrocytos and caiife enlsrgpTnenr of thi? splepn 
and livtr, while othpi' orjiontt urn affected to n 
m«oh loes d^igrw a* n nila, ITio pneumococctii 
h«» a great aflinity for the pulinoTinn' ti»«^ue siid 
for cndothclinl !itmttiir«; it frcquttitiy cauei** 

VL^Td7fJSOV8 tyFBcTtoyg. 


in^iUfl nnd in pi^esent in Ihe blood in \-irtualiy 
til fA>4fl of pn^mmonift. The gottocooczis, aside 
from it* pwdilectiou for ihv ureOira. readily 
liMoxnM lot^aliMit ill the joints, and occii^ormllv on 
xhf YBlvr* cjf the benft Tin* TniiTO-orgiinism which 
anft«S acute eiticular rlifitimatipm ho^ o spcciifc 
iffinity for tlu^ joinU and eDdocarduim. It wmild 
tcttn thai till; viiUH cf hjdrophiibia nLUck? thv ccn- 
ml nervous 4v*tem aEmoFt to thr c:tchi>^ion of 
otW lifiati^. The apirDchete nf ^}phiiU, slthongh 
it maj CAUM dmnifi^si itj «uy wgan of the body, is 
|«nicii1aTly proaii to produf^n pro] if oration of the 
raamlar eDdotheliimi and suhrWolhftial rormfct- 

The fiiDCi whidl coue© pitynnfli* versii^rjlor. ^ajmnenw 
rtoguunti, bjidrHrM itcli^ rTrytlu'urttna rmd favutt 
attack only the cutancou* Kurfaccv. Uirf^n'om in 
IM child i« f r<ine to bo litntl^d to t1i? ^calp, vherwc 
in tbe aduU it occurs more comuiijulv un tht 
niKkoUi akin^ In i'in;;A'c-nn nnd pityrinittK wrn- 
color only tlip ^upprtTcijil skin h involved, and in 9Kla> 
tiie fonner the bair folliciee and tbe hain* I& 
ftvoa and barbcrV itch the ciitii rrra it often 
invftdtdp niid in thr rnrtni:-r hrnling irjiunlly tnkcvt 
plaoe with &car formfltion. Tho oriranieme ftppar- 
eatiy nerer bocorae genernlly distHbutt^d in thv 
body, and ncT«, or rarely, cau^c Fjniptom* of ajen- 
tt%] ititoxir^otion, 

Thcn^ 0rp miny othtr nrgnniitmi: of moro general 
pathogenic powcn whbii frequently cnnxr inf«o 
ttoiu in the i^kin nnd other inpcrfiHot tiaenca. 
although tliey haw no upecifie rtlnlioufihip to the 
cddii. llicT crc fouDd now ia one tissue and now 
in aDotl)«r, and may in fact inrado any orfcan of 
the body. Sveh organUm* nr^ the rtri'ptof'ncci 


isrBcrros a2>d tstMusiry- 

Infppf I'm 11 nd 

InlAvlimf Ion 

(eryeipclae) . eUph_v)ococoi (acsic, furuaculoaifl), 

tlie bai*illu» cf untfinii ( ii^uligiiHiit <:arhu[v?Ti!)« tbo 
tubercle bacillus (lupus, a&ntomic tnberck), blotto- 
niycGt^, lutd otben. It is a rather poouliar 
feuturv of tuliKfi^ulosi* niul lilustomji^osiit UiaK 
Eprcn D primary infccti<}n of tlic r-kin, Uinr<: is. not 
n markecl fHspnsitton to the m^trtfitfttic invufiior of 
iieejivr and remote tiaaui-e, Thia docif occur occa- 
«iona)lvT it it true, but it Mcn^niA that n primary 
liicflli^fltiim in llin fkiu hHs » tPHrlonrj In immuTi]/* 
Uw rest of the bddv against kavAfiiaii by thc#t 

I3i[j|ilhi-ria and tetnntu, nf Msted elsewhere^ rqi' 
nyi(:nt ojiotlicr type of lofcil tufcction, the fonii*r 
involvin;* muc-ous ftiirfacoe, the latter hiding a wound 
infrt'tiijti. In thi?m>r the nr^]ii]i>mfl dti not hp^-tkrii^ 
gciiernlly dis^tnbuttd in tht^ body, or. at Jiny n\e. 
not to a mnrki^cl and ««flontial drrgroo, but tbc gon- 
tral into:ilcatiriD resulU from Hie ai:-tJou of »ipeoific 
•olublo toxins ^hifh arc uhaorbvd and distributed 
through thp body by th^ eirculitioii. The orgen- 
isiiui are largely limited to the point of primary 
jnvaaion or im|)liiDtuiion. Their toiine may be 
obtnincrl frtf from lb** |ja<?lM-iftl n.'\U tn arlifi^^Eftl 
ctiUure media, and biicIi toitirt^ when injected art 
able lo cause the aymptome of tho di»^aj?e, 

The biHIliis nf bntitliMiri hplnng* l<> tJiP fcamsi 
i:roup oji the tetanuB and diptitheria baciMue, in 
that it prudiiC(?g a ep^ifiL' soluble loxtti In culture 
niv^diu uhiih is able to cnLisi^ the syniptoTn^ of tb« 
disease. The mcchnnism of pothogcncais ie differ^ 
cut, ho^i-ever The toxin which produces tho dis- 
ease hftj" already been formed in the di^cnaed meat 
by the bocillue boforo the meat ia oat^n. and the 
puirionin^ TCflult^ from the absoqitton of this toxin 



WSt)^ Uie vail or tJie intttitiDeK The bii(;il1u9 
itwlt k hehevtd not to i^rolifcratc in the ictcfl- 
tiniv. The coTulitioQ ii onn of intoKu^tion with' 
out tnic iufectign. 

In some of the iatofttilial di^^oaca the cavity of 
tiic intotinet appcan to ft?t u a tort cf rvAurvotr 
in wliich the organiMmB proliferate to aii unliTtiJtircl 
dttSTM, and from wtiicli thc^ rcuch the circulation 
nnore or l«« oontinoouely in torg« numbem^ cither 
in a lirlug ur thud r-uiiiliLiori. Tliin rr^luleH pi^itlcu- 
Mf to tyjihoid, paratyphoid, cliolcra and ilyJCD- 
lcr}\ They Ar« priinarily surface inflations. In 
Lbe two totmrTf honnci, the orgnDitm.^ during 
tte early d5>* of infccticiE, roaoh the cimjbtion in 
i living coR^hloff) \n large number, anH may even 
proliferate in this silnation. In cIioIctji, the vibrios 
iltoiT A dixpcititioii to ^^^norni invafticnj hnt npprnr 
U h& killeil olT before they have nolually ]wiw- 
tn1«cl UvG ibteatinal valL 1'hc fiAinc condition 
jirobably proratU in bnctllnry dynntory. It In tlio 
£tnier«] belief thai the iDtoxIcitioQ in the«c 
iartsiCM c«[D«e about through the diaintei^vation 
of thp iritL^rn-orgjiiiiiiriiSr ua a ouriHc>i|Lki^i:iC(< of ivhii'li 
apoiK^noiiv protopUam in set free. Thi» conception 
hJU iti origin from (bo facts that it hfl« been diffi- 
cult or iinpohbtbltf III iibtjin ptjlejil Miluble toxins 
in culture mcdm. nad that the bcHhca of tho kxUt'.d 
aTfonUxus are ^iifflciontly toxic <«* evplnin the 
inioilcatioD. R«ccnt wurk^ bowei«i, indicate* that 
4 c«rUiD quantity of toxin nifty ha produced in arli- 
fldal ciiHivjttJon, »nd il U ptwjiiMc thiit Jlw trinili- 
tions in the body are much ninrc favoi^nblf' tfft 
loiin produf'tton than ure artideUl itirroiiadEDjT'. 

Certain clironicitifn'Uons r;i'rn when IIjcv involve 
deeper tiuii«c and internal orgsnB. thow from the 

rrikn n 



i\FKCTio\ ixfi tMMiTjitrr. 


AUrt fl dispoaittOD to reuiaici localijted. dUiongb ii 
liie ^nd ttipy tnav lovolvt rftricvv orpiuit, b>* tuMffii 
or inctftjilnfars. nnd in Mfm« of tljcni a more or \f^ 
continuous blood iDfcv^tion mty nhftc. Sudi dJ4- 
enses are tob^rculosiit, a^rtinoinyooila, blt*Uimjeo- 
sid (oidiomj-cMii)^ rKiso«c1craini, sporctncho«u, 
and porbope Jcprot}. llicj &r« cboractoriMd by 
tlie foniiution of a ^'ood dejil of fihranA tiHne, 
which iti\da to limit rapid cxtuiEiioa by the forma- 
tion of m^U^lnso^, nnd b^ n diGpoAttion to iuvade 
cont'^ouij tis&Lic5. Now foci ma^ be ^td up tn 
dJ^Dt organs by iiifiana of motafitseU, tbe blood- 
stream itt the meantiiTit' bt*lii;i yOTiipuniliTely frc? 
from living micro-orgenj^ms, A true septicemic 
condition may he pfoducod in tubercti]o«ig by tlic 
iikddm poumjf of \atgc (luititliCica of bacilli in(j> 
the piroulatLDTi from a chccij focus ^vhich h«fl 
niptiirdd into a v^stcL Thin ngain r^gnltt in tbo 
fLinuatioa of m&ny minute foci in varioiu iittit* 
of the body I'dilTuwc miliary lubtreuloti*). The 
umditicinri nrr ^iniihir in blHKlmiiynjKiK^ TppnoHv 
and glanders Hardy mctflBtatic infection with 
actinomycea is found, 

Tliew dii'oiik infections are not the only ones, 
boverer. id nbich ncv foci may orisintt« bj 
rarifliftfi*je. A etix^pt&ooeeiw infecticn of the boart 
\;ilvt<i4, or an infected ihrombna in Hninr vein, tniiw 
"pvrmi<:'' abnajfiacs in I'flnuufl orgaufl vibi?n infected 
c\f}U from the original eile are ^*fl free in the circu- 
lation. The foci of infection found in tbp kitlney in 
typhoid fever, and tlie in\olvement of the joints 
in gonorrheHj are fui-Uic-c examples of luetastatie 

As already indioited. syetemic infection may 
lake plai>e in a feconrlan- nnd jie^^id^nul way to 


gYatEMSC i^t'£CTlOh'g. 


mtay cn^s wbni a pre-CTisling locnl diac^ji^ exists 
at iOOM point In o ^tiiaII gr»>^ip of dUenf^a 

Ary general iDTasion occurs wjth ^rcat cranataQc^', 
and the organicnis rsn nlways be nillivnt^ fwm 
the blood if this U underUken at the proper tim«* 
In sjpliilic gcn«i'il mva^ion ooeur* only aftJ^r a 
certflin '*incubHtioii iiciJcxP hue b<vn pnML'ti in 
the prinary core, and after tJiie time it exieta a^ a 
protracted blood Inf^otlon. 

Others appear to b« priiuarllj and oseaDtialJj Jl^^^l^ 
blood uifeciioiiB, UMh or no n>action taking plan ibi«ciIo«4. 
at the potDt of invjiikicjn, ThU is true of lyMtJemic 
plagiic, anthrai, Itocky Mountain spotted fever, 
nunc TtTj viTnltTtt mfectiona with tho Mtcptoccc- 
ru*, n-lnpnin^f frvio-, niiil in rminy [if thi? i>rotuKoau 
infections ^ in mnlanAn ptrDplA^Tnofin. ntLd in 
tlMpin; aick&ecs. In eome of th»« th« organiHine 
ntajr paM m portlun vf Uic iucubuUoTi period 
in the iynaph gtjiitd», where they prultfcratc 
lo <uch an eilent that they gTBdnally over- 
ttbeltn the circulation iti lur^j^e numbcn. Tlic 
organinm of inaiaria and ptropIu^moBift prcjh finite 
iu tin blood*0tr«ani. i. c, witliJn the erytiiroiyteH. 
U also accoia probable that the otUcv orgam^rn^ 
mcnUoned ntt able to proliferate in tfi« plairna^ 
aK)d that tlicir pr^Knce in t!ie bbod- stream is not 
du« entirely to their continuoua escape from such 
wlid ufgana m the lymph ^land-i nnd uplcm, or 
frotfn Iho point of primary inta^ion* They arc true 
or full partfit^B in the ftemo of Bail. 

From th* ^tandprnnl of ™ntiTi«rty there are wt- 
cra) CypcA of ayittcmic infection. 

We mav, in the first plfloc, reeo^niie the coTitinu- TriMi»i«B4.Bi 


l\fSCTlO\ ASD jUiiVXttY. 

iho itifoctioD tcrmiDat^e either in death or iworeij, 
in till* lalt*r ease being 9xL«nnUi«t«i1 bv flie pro- 
Wtivc agencies of tlic blootl Typhoiit ond |?nio- 
typhoid fflver, plngue, Itockj Mouiii«in epcitte^ 
fever, Malta f*ver, auO jji^jbabh the acioU- i-\)intbi-- 
maU, are af thie type. Hccvvery and the Mcrilixa* 
tmn of the MoucI, howovei*, do^ not rnenn thnt the 
whole boiJy f* neceeaarJK lid of llie micro-oi'gan- 
isnie; lie latt<;]' aljll mav poniKt for n Ricflli^ or 
\v!w jH^riul on tjtin or mmv ijf tli? boily siirfncec, nfi 
ta the can of typhoid fe«r, in which the bacilli 
may peroiet in tbe intestine* or the bladder for a 
luiit; puriuci. or m phiKUc in whii^li Uic or^aiii^tiii^ 
inuy be found in the epiitiiin for sonic time. 
Through Ktime acHdent tj^ihoid may vary from its 
usual habit, a point which is illustrated hy the 
oeoa^ionaJ orcupmneu of rirlnpecp, or by the locNili- 
nutioji of tie bni^illi in ^wav Nolid organ of Uiu 
body. QB ill the ^'ertebi* or the muaclea, resulting 
in poit- typhoid a! t^mplii^alioni'. 

Ill (illit-r inatAiuii*Ji IJie sytitf*mic invqHEon i* of 
[verlodic rhar^cter, and of tbb tht-re ar? a niimbcT 
of variotieE. The itreplococous, wheo it ♦lists &i 
the eaitee of Ohrinou^ endoeanliti^ or of tbi^mbo- 
pblnKil]>, oflrn invades the circulation ia a fluctu- 
ating manner. JVriods when there are very fow 
vaue'i ill the bltHfcl *ill be fulfowei.i by olliPi^ in 
which Uicy arc \-cry numerous, and the cimtcal 
Avrnptomn nstmlly corn»K|X)nc1 nitb theKv finetun* 
Uou*. A similar i^iir^e probably is followed by 
tabcrenluwi* imd b I u^'lo mycosis in Iheir invaeion of 
tb(? blnod Mrrliiminil frn't^tm sumctimr'* pro^tipi- 
Mr. a «\0temtc distribution, euch an the nipturc of 
a ca^t^uf nodule into i r^^^cl or lymph rhanncl in 



tuiMirc»losi«, or tlitf fepBtHlian of iniuute frD^iuenU 
<4 tlirofnbiw iDfci:tcd with »1teptcc€c«i. 

ExtmpJot of P mote or less reeulAr wfiaJloitv nesaUF 
Mtv foiiBil in Ihr Tnnoiis relipsmg fever.^ avIiicIi 
an c«t]|«d by 0pinlla» The first attack of the 
European retapcizig f«\«r laata for *ix or ^ven 
dan, Tliia h followetl by a perimt of n|>>rt'xl& of 
Rt« or fix daye, followed by anothor fcbiile poriwl, 
Kvcovery E!I uaualt} established afl^i tlire<^ or four 
fddi tttick«. In ihs relaiising fever of .South 
IfricA the Urat flttack han a shorter duratioti 
{atKiiK ihr^ days), and tIro»v whic^h huoc^ may 
\aai only one or two d&\&, orcordinj; to Koch. 
PnriQg tlL« ffljril^ attsrW Th^ blood Rwarms with 
spLrilla. whert^Ai m tl>e iIlt1?^^'ala it ia t^omparft' 
tlrdy free from orKanianm. IncxpIcnatioD of thifi 
it hjiE ()n>n ftutinipd thnt th^ fnhrilp alta^-lv^ are nu 
ibort by the devcloi-ment of a certain degfce of 
inunanktr. I'bia r«sul1a \n a moro or le^e eomplote 
vtvrilijtfltion of Ww Mnod^ nitlmngh spirilln uhich 
reraftin to the lymphoid organa. particularly the 
iplwo, >ooai to be protected. At the time of a 
rdspn^ either Ihe iEnmnnity hnn drrrefi^eri hiiEH- 
danflr, or the remaining or^gani^ma have ^ined in 
flrulencv ro tMoh an extent that a j^neral reinTS- 
men takes place^ In the end t])« immune forces 
iram the upper hand and the body becomes com- 
pleldy (terilised. 

Sdnie of the chnjnle infectioua are subject to 
irrc^Jar recnidcsccncca. Syphiliji nnd Irypanoso* 
miaaU of man begin aa nculo infMtion^. After 
tJiv Bcnte tMxiiidary atn^e lian aj}pNrvat1y paHH-d, 
ejphihtics frcqtiPnUy mlfer reerudcjcencej*, with 
gnwral mnnif«<?tation«p and it is probable that th« 
nntislKt of ujicxo-oTganianiA in the bloorl int^TeaHca 

Dn#«* In 


/.vracnav AAD IMVUSlTf, 

ItLrjmlan In 

fit iti-icb timce. In Ihc iirfet eto^ of ^eeprng «ic 
Ti«BS. Iha so-(«lled trypanoMmfttic tever. th« f^ver 
U of a rcmiltcnt tyjir, nod during the altscke of 
fever the number of trypautMomc^ in Uic blood 
inrvpRse*". In tlit ftflg* 0/ slwpiiig Melrnp*,i: tlipv 
appeur lo be limiti^d vtry largely lo the lyaiplialie 
^londs niid the mcningi«. Thc^ can readily be 
oblaJDed froio tiieso fite» bjr punetiife, liot their 
pie*cnc« in the blood ie much more inconfllant. It 
hut been tbc exporit'noe that on *omo days pro* 
longed examination of the blood will dUcToM no 
trt^ieti^oniee ; on other days two or three per field 
mav be found; (in<! on •till otlers as nmny a» fteveii 
or eight per field. 

The ttTrbnn nnd qunpton inferlioiw witii the 
mslaml parjiRiteP, nt le«=t in tlifir p«rly *tjig**, 
illustrate a ftpecUI type of recurrent geaemliicri 
iDf<H^tion, whirl] it pyclle in nature, Oic period of 
intijiT-e geiierni inv*ifiinri criiicHlinj: wjth a irerlain 
fita^c of tht^ hE^_\iia[ fnuItiplicDtir^D of the paraeilcfi. 
{Sw ehapter ca molarEa,) 

(.t) Nat'ure-- and Mf-rhanista of inferiloft, 

iVpi><rttHi>ii Uf ^* ** t** ^* nndcretood tbnt infsetion prcauppose* 
nict'ri' ;i penetration of the bodv surfaces to a creator or 
Ic^ dtgree. Even \n pityniiais versicolor, the 
mo*t auperdcrtal of ipfe^rlioas. the (iim^iis peiie- 
tvntiTTi thi? Iiomy ]nyvv of the skiii. Hence, in a 
coneideration of the nature and inccbaniem of 
inftct&on, it \rould he di*»imhhs firjit of all, to eou< 
fjdcr the manrer in vrhicli ]nkTO-or)zant£m?= and 
their poifona rony reaeh the deeper tjesues. In 
tiome Iii^taiit'e-i tliii it ivndily l1tlde^^lol]|]. vli^ii^s 
in manv othora >ve inu«t iu the nmiu be eontent 
with m?re deduct wu*- 







jiyjtr, penetrate the mjrfocij through mcchnnicnl 
dpf&yu of their own inflkitig. 

In ppHptrnting wmitiHs Jthnwionii And triinsinjiii- f'**^!^^'*,' 
«oo by im«ct8 ihe jnlroduction of microor^niiTn^ 
U a quortion of mcehank-a] Inoc^iUatioUp or aiibfip- 
rjijunt J£rD^vUl into iht^ ilrfinit. In Uii^ ciuie Uicrfi la 
DO barrier to thoir entrnnoc into fho cireuUtion, 
unlii aUvt tlie hppfiirao** of nn irirnniintti'>rv 
itactiou; and if tlie organism bapiteue to h& ont 
vhidi fttcratoA a wlubU nnd ouilr ditTuftlblo toxlD 
<e. g,, l^ttn^s bacilh]»), goneml inti):cication may 
itddlt GTm iritliout furtlicr dieeomi nation of tho 
Urin^ aeU», Thc^ d«grp& ^f tlvf^^i iicL-ewuiy fuv 
tnfcctioii TUiM with the character and rimUncc of 
tbe orjuaniftDi. Ilie baoiUi of plagii^', anthrat, 
ghoden, and Ihv ^plrodivte of s^pliilis iimjt tauter 
throv^fh If^Aicns vrhith are almoBt microdcopic in 
»iip, TliM^ organism* pfK««si groat inf<»ftivitj', 
exceedingly email nnjul>ere producing infection. 

Orfcantimv, audi ttt virulent eituphy lot? »<:<■], which 
r^eh th^ hair folliHes anri flchnrficnis gfanilti. nrr 
able to grow tlirciigb the snt-culent cpitWiuiri into 
Ibe tmrrouodinf- tia»ijc«, and to cauje a. furuncli.*, 
nrtmndtf or cclhilitiK- ThU inny UtiUm or bt 
aocompeiLied by a primarv necrosis of the opi- 
tbcliam. Ocvafiionaliv vhen fiiriLncl^Q are iitiijit«d 
at favornblc vpob. aa ncbr tlie angle of tlic moiitli 
or no««, th« DwrofiiE may ctt4nd to adjacent voini, 
mulling in a flooding of tlie circnletiou urith the 

Tn>« eoliible lotin* arc eeldom ab«orbad through 
tbe nnbrokm skin, H vsr i-Mtpl llu? va*e at poUon- 
ing with poiAon itv- ir Mnrd"* tcrt for tuherc^do- 
tia th* ti)bercti]in. inrc^rpnrnted in a pa^t^. i« 


l*iriivirHildii ItT 

Cflll |I|C<IVUB 


/iVyjTcr/o.v a\'v iv^vsnv, 



rubUctI into llicr skin. Tliu :» aI^o true of n)(»t 
chcmioal poi^ume which do ii<4 have o corrosive 
yffw:?, jilftmu^b hy pmloniw'd [Contact (Wd) or 
rulbiiiy (nicrcui'j) n ctrtoin oiiiount of ebforp- 
don nmv be mducod. 

In infectiont of the iuui^ovia iiiembranee. with 
tlieir loft epithelid cotcilug nud moist Aurfaco, 
niicrO'or^nniciiiR aro ofttm nbto to groAV throti^h 
iniit tb« untTiT Idling tiwue, ve^itltiog lu clllipr ;i 
local inflaiiinitftioo, a ^tierat iufectiim throvigh 
the medium of Ulo lymfilifltiod or eapiltani**, or n 
^jlctaI lEitaiLiratiori throug^i Ukt> shaoiption of 
toxinn. A meclianiont defect in the siirfdcc nuiy 
iioi hv tivcva-iiii-y for 1liir^ jieiu-lrjilion^ i\\t i?ittii- 
Mfiti Inking plmc hy (onttguous growth, which, 
liowevor, la snroly Invoied bj anj toxic and d©ii<[iia- 
mating effect whidi Ui* orgHuiaui or it* loiin luaj 
hare on tht^ epithelium. Streptococci which reach 
Uio rtj'pts of fhfl toD*il* r^idily canto nccrrwU of 
the surface epithHiuut, and this defect irould Bei*iii 
to facihtatc tlocpcr invaeiou. 

Tlie growth of the diphtheria bflci3his ia limited 
In thr main lo lli*^ *Lipern<ial Iflvera of the tmiiea 
which it nttnckf, Ae the or;;iin]sm penetrate* tho 
epitheTiHl layer. |;i068ibly by direct gnifltli, the toxin 
which it Mcretes causes necroeia of the adjacent 
cdl«. This pT^C9U continuc'H until the vuioulur 
fi**n*^ii t\tf* renclied, I'psuitir;; in the formntion of a 
ffllec membrane. However, the oneet of fovor 
before the formation of the membrane, and the 
occiirrencc of dipbthrrin "nithont membrane formA- 
liOD, thow Ihflt the injse membrsne, i, G„ tho necro- 
eid of (he buifm-f. ift ijy iiu JiieHiiH a |iL'erei|itinilti for 
Ihc ahtorption of the toxin. A ncvcru mvuion of 
1h« body by the baHllite Hoea nol ot^ir, although 

lEVCOCVTiSS AS CAIti:it:tftt. 


oacuiooal iQiIividoals, without ilotibi, rv«c1i the cit- 
cubtioa; thif, harw&r, M ftot Deoett»ary for th* 
general in toxica tioD. 

J^eiicocvlt^s art ooDtJauuubl)' pdAsiug frpni lUt- 
lOMla, iDlrttmca and other nupcTfitMnl or;*uDs 
vhtcb am rich In ljFin£kliAiics« thrciiigh th^ riiir«]ii8 
nMal>raDe to the surface. Th«M «3crvt«d leiic^ 
e]Flt0 nay otXta be c«e& eofl^n^ villi larfjc num- 
brr» ol bnctcrift whirh thrv mi^oiirtiT or tli** »iir- 
focc, and it has htxn aiiggcatcd thai the €icre1ed 
leucocytes luay r^ent«r tho adjaceut tiseiue. carr}'' 
inf; iMctrxia with tlitm. Thr wixi6y of Jii^^tiona of 
the intaatincf, toiuiU and pt^nbronchial lympl^ 
ghrada haa ahown tliat liai-t^rj^ are contimiouih 
^nterinK the body, even in health, it&d their fr«* 
qnptnt occurrence within Ivuc^oc^yt^j; which iir« neat 
the trurface ati^^ftila that iJte lattti ait? tlie ugvnU 
tl)rouj;h ^hich thev are intr1^duccd (ItulTer. Bix- 
tmcn and oth^rw). ThiK finding, how^r^r, cniilf! 
not be acc^tetl ab jiioof of the hypothesis aiiice 
the pbogoc^toBts may hav« tak«ii pluco ufler the 
orgMn'vm* had pniWralnl thi- vurfiicr in'1{-|>pnd< 
,Tlirou^ th^ work of Xoeard, Uavcnol, Boluing 
oih«r». It haa been iliowii that tubercle haeilli 

It pats into tlie l^mphaticf from the intcstinas, 
in the abMncc of mcohanioal defcet^. 

That the Icucccytcfl may perform thia function 
U also BU^eftf^rl tiv A> D, MitmHinn*!! :<lu(lv of ttir 
nbeorpliovi of uon. When the nlhuminat*? and pcp- 
toMtc of iron were fed to f^tarved lizards, the mic- 
eraL eight hour* later, m\% dcnkon^^tratecl in large 
quantities in the leiic>ocyt^ contained in the lum^n 
of Ua^ iDti>>lin4*^, alao witliiQ Wcocvlet which lny 
bt^ttn tbr qiithdinl oclU of the rilji (rc-cnlrring 


isfTci'wy aS'D jM^v^n'Y, 



leucoc^iei (!),flnd vilhin eimUarMlU whioh wen 
found In Uie li^et and ajiWn (Ad4iui*« PrmdpleA 
of rutliolofTjr', Vo). J, p. :E9I). Inaimuch qa nu 

poAvrr nf ii[iontnnp(ii)H [wrrlrBtiiin van bp jiJfrLlirjl 
to the par^cJee of u'on. ^t i» held ihnt tJiey licre 
cArHed Int3 iJio liiwutfa b}' inwaod^rEDg teuocM^ytcA. 

It tnnv he ntutrd, then, ni< n rrMjaoiiahh'. prubnlvil' 
ity timt mioro-organiiitiifi ore toisetim^ carriod into 
tlie (levjier tiK^iie^ hy leucoojt** which r^nsnter ihv 

PhAgocytoei^ at bacteria by epithelial ceJIfli par- 
tifTiiUrlv li^ Oil' ijulinoriary c^pitlieliuiti, h known to 
occur, but it i* not known that the procc** u ttn 
t?f«?iitiFi1 on$ for invasion. 

Snmr lusinu urn Tiot rpjiilily almoHind hy ihc nor- 
mal miieoufl racnibrflne^, w[icrD4» othme fie«m to be 
taken u|> rondily. In the abs(!T]('i< of ivoundi. Ut- 
nn\i^ ItAiii, wlirti tnjci4tril> uiiiiwn no vyiu\fioxiw. 
It ifi destroyed larucSy by tlic goptric otid paa- 
crcatic JaioM, and th5» If tU« ca«« also vith dij^V 
th^iTift toxin ir tc^t-tiibc experiment*- The latter 
haA the powor of oauein^ recropi» of the imicoea. 
and mity he abiwrbul tlirtjii^li (lie injirreil mirfan^- 
Thc toxin of liny ff^vcr ia readily abj»ort>cil t^iroufh 
th« conjunctiva and the miicoua mcmhriin^ of t}i« 
iioAv. KKftt^ri[tLtntalI.Vr lidu. n plaxii to\Jn. t» 
ab£orb<?d thruit^U the inlcHmc!, oltbou^-Ii the 
nmniiTit n>^U]rtd for Uin] [ntoxieation by thU 
ronie greatly exceed* that of the ^abciitaneoua 
injection, Thj> toxia of the bJieilltxA of botuliFm 
in miulJIy iil)Kr>rh<il Oimn^h tJii! iiitt'jiiinpM of hnih 
man and imixnaiB. 

VTben a niicro-orgnni«ci confte»= a primary 3ea- 
quuiiiAtion of thi^ miicaim epitheljiitn, it falTowa 
that further ppnctrnlion nf the nrgflnism, ait tt'cH 


tyCUB,iTlQy I'EitlttD. 


H ttbeorptioD of toiind, itr« focititotod. This woliIH 
*wm 10 find iptielal ik{jplicfittoti in r^holera and 
bftciiJniy difKiitrrf, [ji rhoEcrn gcni^rAl mvfuion 
&f the Iko^y bv the living H>i-gniiismE doi^j^ not tak9 
pj<c*, Kltljuiiyh thf iute^tJua] eurfaou za deimJei] 
to a gr«nt«r or icp^ degree. The vibnos |x;Dctroto 
lo II eortflin mth^r stipe rflf^in! d^ptli, wh^9 th^y 
ippear to become dlsolvecli adi! vviUi their disfolu- 
Ikin, pcieontt, in adJJticu lo tlicic wlritb wcro ptc 
vionjilv H'cn'twl, rare »et free. Tlif? ['undititiriK am 
similar in dtsenterj'. 

To pmniii-)firi^ TincTo-orgfitiiem£ urnin (^ntraucc t^ ««iiiBi«»r> 
ih* »iilbjacenL lissuep t hrough w quhIs, b> irn'-nnc nf 
tktlt owa power of injuring iJic eurfocc and ^tow- 
tag into end through it; ond |ir6fjab!y~v1«o through 
ihti agency of inwonJcring leucncylcf. Phn^ooj-tic 
eijitli<^3ifl) celJa id ;onii? inalaiice^ imy f^Ia^ a part, 
Uol tlif» is li_v[)utlM*tieKJ. To^iiK arv iih?torhi*'l foi- 
the mcdt piirt throiifh »uriiirra which hnrc been 
pTVVfrouslj injarett, but «ome of them are able to 
poes through previously b^lth^ inuroud mt^iu- 

The terra in<3abatioo period ^ipiitier tlie lou^r- 
Ttl betwecEt tiic first ititraduction of n pnUio^i^ru: 
micTo-OT^ninn, or its tonn, until tlic develop- 
m^t of the flr«l ff^ptcms which charaMori^i^ tho 
ovwet of the dilute. En jnany mUtiwnji, n« in 
typhoid fever, a feelln;; of maliiTsc, hpuclfldio rwI 
ttttiMen^ freijUfrTilly appear a fev dav« lefoi^ riiar-k^] 
symptomi develop, acd tbu period it cnllrrl the 
pTodrornnl i^nije. It nmy bo conRi<?ered titlior n^ 
tho Uttrr rnd uf Ihr^ irii-nihHtion pi'tinil, ur nn tin? 
begimung of fictual "onset," 

The leDirth of the nicub«t30D period variofl nnMii*« 
^Ptttly In difTt^n^nt inr^ciLCiu. lit cholera It may 




he ai *hort is a tevr houre cnl;, in hydrophoSia it 
b on r*re orrrn^inDs as loDg a» six mnntlks, but 
moru commonly two to four v«ek0. )a o tstbcr 
largi> group of diwflie* the oiwcl follow* io from 
oae to two ir«ek« after ei^pofure, lO tliat tljcK 
would Bocm to be ii tcndcnoy to come j;«iicral la^r, 
tho baeJB of which h not kDown. 

It hn* twcn *ii^ip*U'(l l^lnt it iimy linvc u relation 
to flio &napliyUctic reaction (Hokdou and Aiidcr- 
•on) ; namely, ihftt tlie fim micro-organisms intro- 
duccd "scnaiitiw" the bocly in sotn^ wny not yH 
undorftood, ftrd whmi «aifiih7fltion hoe taken placo 
(wven xo imiH€£ii dayn) tlie boily tlien liu d 
greater &nw?cptibihiy to tJic organism ami yielda 
rearlity lo infedlion (floe '^Anjiphylnxis'^). 

Oivasioniil inilividoRlii ulicw h miiruptiliility to ii 
iSr&t injection of liorae fcrum fc, g., diphtlimo 
antitoxin) in that Ihey develop an urticarial rflfih, 
ddcuopAthy, (-ITusions into Llie jnint?, atid pLThnpA 
fever, in from eight to twtlvc Hnvfl nftor the intio- 
^tiction of tlip senim. Von Vir^jiift noted tlific 
when n second injection of the serum vas given 
aftor All intcrvnl of two wccke or mors eimJlor 
siymptorus woirld rlevelop within a few lioiini rather 
than artt-T Hovcral day^i and there is a gToat deal 
of con»taroy m this whti: susceptible indinJuale 
ara concerned. lie arrived at the conclusion thot the 
hor^o aenim aa nKh is not to\ic for man, but tliat 
aa a conver^iienc^ ot the inj^^lion antibodk^'i to the 
icrnm are formed and that the intcxicntion comea 
about aa a r«su]t of lomc kind cf oh^mical reaction 
which take* place between the antibodies and thL- 
»orum. Tlie ecdiditioua in immuniaation render 
thJN osplanafion evln*mely prr»ti»blt-\ Aftor tho 
first injeclion of ionmi antilodica to lbs aeram 




'^^iKdpUatiDg and perhnps other AuiibiyWas) are 
found 111 couudernble ci>iictQtnition m the blood 
only ofUr tfcc Lapw of t^omit daye. If the iojectioD 
of serum ^vcn in the flrjit pliu'i^ was of FAiii«f site, 
wme of th« ori|£:iM] Borain protmds would still be 
pndont Id the t>ody vlien the antibod)' foTniation 
hid Toadied a high |ic>Int, nii'l the coDditione for 
tbo toxicogoDio rcactJon (xstwccn the tno would be 
proaent. Tl^ia wottld aroouDt for the d^Iavcd reac- 
tioa ve^ in firdit iiij«ctiotia. If ftome smaller (]\jaii- 
U^ wvra given in the Hrst pla^c tbo delnyod r^MC' 
tion might not occijr, bccaii*ie tlir scmin proti^id* 
w^uid all have been modified or excreted. If a 
lacood fiiJffctioiL i* gii'en, howtver, the tmh nenim 
at once com«i in contftct with the antibodic!^ whidi 
have alreadj bwn fonn«d| and tlia toxic conilina' 
tion Of huh-ttaDL-fi can be produced at vin:v. 

On the boflifl of tLeee conai derations von Tiiquot 
belierea that the ordinary iDtarpretationi of Uie 
ttatare oi Lhc luculinliun period nw im^irrix't, 
Aa iio itty<: "I pre^nted the thcorv tliat the dis- 
■VMi>-prndTirir!g ag:ent only ntlU forth pathological 
BjinptonuA Jn llio body when it ia changed by means 
of Xhi antibodica; the iucubalion penod ta tli4 
period rcquirvd for thr ronnetion of iheae auti- 
bodicf.'* Tbi* po^ibility cannot be o\erlooked 
in a pr^4eTit-day conaidfrratioti of thU subject^ 
although it itf atilJ on a theoreticnl foundation. 

The Dtioibcr of raicn^^or^Aniam^ introduced has 
an inilu^ce on the incubalion period. Uuin^n- 
pi^ may be icilkM] vJthin a frw hdiirH hy th« in^w- 
lioD of a Jarg« quantity of typhoid baciUi, but with 
tbo adminirtnition of t^malUr rjtiantitip^ a tniich 
loDger incubation |*i?rlo<i nuiy be frblAiiiHl. The 
affect cf qtiantity ni**> ji «Jiovn very dearly by the 



injectioji of diphtberifl or tetanui tojitf)*, by ttUidi 
tht incubAtion period Cfta be ahoiicncd from k^- 
<im] (lft}ii ^ovn tn Fevpnl hour, dep«ndbg on lh« 
^uantiQr injected. 

rh« £o-caJioil tni4 tcxiD« cf bactoTiA, L «., tho^ 
which are Me to cBOse th« formauon ol imlitoiiiu. 
a? a rule are iiUtu]j:ai»Jieil from oLIicr {^oiiioiiotif 
€ubEtaiioG*^ of bflk^terial or ctlicr origin, bv the occur- 
fmce of an inc-ubBtJoQ j^eriod wheu they ai-e B^niin* 
Utcrcd. Hoircvcr, at least two toxina, rcnom ontl 
that n'C'Tclvd by th« I'T'brii? A'fUTjt aiit^ p«diftp« 
ot^ci vibrof, act »o (|nLcl;ly that an iacubtttioii 
period ifl hardly to bo r«>2ogniM]d. 
Pn>iif*»<i»ii. The number of mtcro-organianka originaUy eater* 
hig the liodv i? EiHuiitly quid' Kraall; hrniM- ihr timr 
retjUJixd far Ibi^tii l*> rmcih en infective or to\ic 
qnantiTv pohnbly repreeenU a pan of the irjcuba* 
tioti perW, 

In hydropiiobia tind ti'toiiu* ■ m^horitoal fac- 
tor plH>» h part in thi? kiigth of Ihie dag^. In 
liiCBO Cflflc* the micro-organiana [bvdrophobia) and 
toxic (tctauut) appear to reach the (^entrol nerr. 
ons i^yjitcm by way of the pcmpbcrol ncrvrv, and 
eyinptom^ an? ddayod until thU occurs, Wounds 
cf llio fdL-e and neck nr^ f^jJIowed by *yfnprom*i 
more quickly IJjan vhta tliey an; situated on part^ 
mora remote from the central norrouH ayvtcrni. 

Tt ti; not tmtikr*ly Oiul »nii[bi--r factor coujsiftt* of 
a certain relation bctvccn the protective power* of 
the ho«t and the iiiva«ve f>r ng^r«»iiv@ ability of 
fhe orff*ini*mj nf. Icjist In ftnne in^aDcc0. Lcmaire 
and also Bu.^cton found that after the injocticu of 
pathogenie iiiicro-orgftniFmB rlinictly mjIu thr rir* 
culalion, tlii'i'c is ai fir*t a redvctirtn in their nnni- 
ber, followed 1^ renewed prolifernlion, which 




itaa^j. Suppoiioclly, tltc natural luti- 
hscivriil foTcei of t1i« %emm &n^ l^ut^ocyiee tixtk 
ap die destruction of the bjiOm uutil tlie formei 
vcr« eih4i;itt«ii, aud from tbi^ tinie proUfcrnlioii 
couUl tflk^ pW(i uiLh litltj* hin^lrAiiri^ [n itxtw- 
tionfl whicJi occur DatDrally. aa in typhoid fever or 
ictrlet itr^Tf tlie first organiame whi(?h reat-li the 
uadcrljifig tiiHUca und circiilulio:] iim^v bi* 
dottrciyod, icrolrtDg sucL a lo^ of bnctcricida] 
•gCDCiee tlint continue! pro] i fern t ion fln^l invA^imn 
finally tt^alU in sencroi iiiffction. 

In epealcin^ of p&K&gt, it lias filreadv bcx'ii 
tliilod Ihiil virtilencr m[iy Iw tncrcJUiHl hy piTiiiit- 
ling uh orgaotfiii to grow iii tbe tiesues of a liviug 
BfumaL Virulent GTf^tautmsi arc not tul^cn ufi by 
ieilcocytee fct> rendily o* avimlentf an*I in Hie prpi- 
eoce of hi^ virulence there may be no plia^ocytoais 
at ftIL Tliii hns d bcnrin^ on the incubatiou pi?nod 
in lliat the inicro-organismH wliich Uni come in 
contA^t wiUi tho ti^aue^ of the tiout may have low 
timleccc, but ofter ^-jtpo^tire to tlii^ gvrniieiilal 
ntbitaiicef for a sufficient Icn^li of timo. their 
ptthogeaioitv and re^tiaEice nia; be 00 raised that 
fhty «aeape dc^trut-tion in tire tiaiiued. On thU 
bui*, tlicrcfon;. the iDCtibAtion pcnot) may. m x^iL 
Kprsfetit the tune ri^qtiired for ihn urgnnUni« to 
bMxriijt r«r villi- rutitiUnt- 

l^cj^ardin;; the auhjoet under diaeuwjon, there i> 
irtill Biiothr^r fmior whiHi Cinil* jip|iHealton, piir- 
lieuUrly where toiina haring an tni&yiDe-like 
nature^ ore involved. Toxin* have been likened to 
Kafmm, bocanw of iticit at^tion in ooerdin^lj 
fntlJ doM«, their common tnu^ccrptihilit^' to hcnl, 
and finally Die «ii;bihiC:on of an innibntion period. 
No ma!trr Low much diphlheria or letannn toxin 




ii mtroduic«d loto in animal, the incubatido peii^ 
eannot be climiiutcd aliio!utd>; anJ ftome of tbo 
licnioljtic loiin*, a* tcUnolvsin, can he sd<1eil to 
r«d blood cclU in ket-ti^^^ ia any d««iTvd quaii^ 
lity wiUiout cauntn^ ihi-ir krtmodiatc ffoluUou. 
Tii**rc ia, tiierefure, >tuEUFlliJiig uilieieut lu tile 
naium of tlicin; «ub»tiincc«p or in tbc tintiirc of the 
action which thev ?vert on the celli of the bodj» 
which dcmaudt^ tTiift latent pcri«Kl Wforc an aff«ct 
l)(^ooinc£ mnnifcftt. 

It itvemt proballi% thcrvforv, that tlierc nre many 
factors vrhich rr>ntrihiitt tr> thr ciirtciKv of tbc 
mcTibntion period, and tbat Ibc factor« v)iieh 
deteniitEiu itit lerif^^Th tn ont* irmtanev may not be 
idcntirn] with ihiMv; which arc found in dinoth«T. 
Thp limo rvf|uirpd for proliferation of tb© micro- 
orgauitiu lu an iufu.'iivr ijuauLiLv jinibiLlil)' i.* t'nni- 
mon to uU lufccttoiid. Thi: infective quantity muat 
vary with iliJTpr^iH (JinptRpj:, and with dllf^rcnl 
»traiii0 cf the: fame uiicro-or-^aQiflm d^p^urling on 
ihcJt virulence. A MHilent rtraiii l\ae a shorfor 
incntmtinn [n-iitHl limn n \m izrulont. In aimn 
inAUtio(3 a certain Amount of tiine may be 
required lor lh« miero-organiem to undergo an 
intreaw in viritlriif<- *Hlliri(-nt ia m-i-'o«npH*h infec- 
tion. Or, o^in, th»B time may b* rc^juirod for ihc 
ox}iaii!it]on (al^^rpllon cr chemLoal binding) of 
the protoctivc nubatanci^ lo 5uch « dr^rcc tliat fur- 
ther proliferation and invasion take place vith 
greater rapidily, this latter it^p minciiliny n\[h 
Uk onset of marked jj-inplom*. The limo required 
for dijtti'ibution of the poiconji to vital orgnne would 
Kfein to be of minor ihipoilant'e «]Lci^pt in hydro- 
phobia and totunuf, v>'Hi(<h ilIiUkc the f>oriphem1 
norvM as a route to th^ o»Rtm] nf^rvoun syttcm. 

AyHyirtt:s of jvjr/A-a 


In tho r»M of lomfl of tlie tr>\inR (us of dfphthpnn 
and teCaniu) a certain tiuie for tlit mfinifci^btioii 
of 1 toxic efltct U rtqiiirtd, cv^u whuo they aro 
pUced ia direct coiilflet witli the c#<lls fr»r which 
ihvy haic A BpcL-ific aflinit}'. Ac slaUd^ U^c fcle of 
aiiaph\]ii:iiti k i[|]i?»rtaiii. 

I>i)viug out of cuTinkki'irtiou dit iw 'iniiiAitOfiA 
m which preformed icains ore ingeslwl oiid 
flWrb«d (fli in botutiain), lh« production of tlh- 
F«BC in n miiiiMfjjtible liojsl would Hctin tij de()eijd oa 
hro factor*: K:rM, prrwnpc in the micro-orgmiisin, 
or wcrvtioti by ix, ^if a iitxjn which is Jihle t» t^utiw 
t dirvct injury of the tiMU^e of ttio liost; and sec- 
ond, ibility of Uio microorKoaitni to r^rnnin aVifB 
Jind to prolifpratn in th« bod/ of tlin hosl. 

Different toiinA nry grcflUy in the cells wHicIi 
ttiAT ittAcic. 9on)A destroy the rod blood l^IIi; to n 
nr>iirVe<l d«';^rtft> (staphyloenccuK and flti'eptocoM.-un) ; 
otlicrc have n apei^iQ] athnitv for the neiTotid ti^iiiK? 
(t^tnnut, diphth^in. tKittilum) ; komc atlitck pnr- 
licularljr tht vDiJothelimn of the vesAeU^ cdiuing 
mmay minute Jicniorrhiifiee (eoinc of the cnsptive 
fmn, rattli-fiiakc vpiioni). U\ niutiy blhiyr iri- 
«t<noM the toxiDs hnv« a ntder langtt of fictton, 
and many difTerent tiaauot iu0f^r to u ^reuter or 
teu dt^E^!. An'flK of iiivToiiiH in Utr lymphoid nnd 
fMTcnchyniatoiifl or^nmi, «rd grannlBr and fatty 
di^eiwntion of the Intt^r. and of the muic*[ca, 
i&cladinj; the heart, aiv wirll known in difTiTnit 
dboiicK. The alhnmin and cnttn which npposr in 
th? nrine in vaHoitb Acote febrile diBe£.eea arv s 
rcflclt of a toxic acticn on tlie opiLhelium atid endo* 
thcHum of the kidni]yii. 

In addition lt> defraying life by Ihair diiwt 
aetion on th« cclliu pathogenic micro-orgnniHin* 

Pan tar ft 





jjfoduci* pn>fuu]kd Oibiui^uicn in oietabolisin and 
nutritioo hy ioWferencc vitb the fui:ctioE]5 of 
orgins. It ii nut l!ii* intentioii, howovi^r, lo «ntor 
into a (])fLCiii»ioii of thv^c obecure mAucmco* 

The mcH^AnicAl injitnc^ whiclt mtcro-f>rj{auidaiB 
v»\\sfi Hr^, nt IpHBt in mtisi rft^«, the re»»3t nf n 
prerioiu t<>xic action, i, e., they ar* ftecoadan 
cflf«cU. Thii i« true of tlie emboli, coDsi^in^ of a 
luWtiirc at Abria, cdU nrid micra-orgiun»m». nlikb 
omc in a rAlmlnr crndoc6rdi1i^« and of thrombi 
whiL^h nre forni*d in reitels an s cunwqiience of 

hi loUr pat-umoDiu wc have a Kood«3tanip!« of* 
itni'hnnical di^iturbHutc ct importaun?. 'i%v wlveoH 
tpccoiDo filled with a ^brinouR and purulent exudate 
vliiob mak&4 a lar^ area of puLmonarv ti^ite 
Mimvailnljlt for rcjtpifwliijn. Yet, t-wu here, llie 
nicchcnicnt diHturburcc hni oripcn oiily m a i-ctfidt 
of th& tp^'ic action of ihir prniTnococcui on T]i« 
capillary \ia\l& and the alveolar epitlietium, per- 
mtttiuj; Ute o^Uj^c of thv b[ood and t^ram. 
Csnii«ciiv« Some chronic infecliopfc »te chnracteriied by the 
dcvdopmcnt of n^w connective ti^ae and veesclft: 
thU h men cvpcciolly m gyphitiE, htbn'culoftU and 
At'linomyfo^iB. The i[n[wn't of the new counwiivt* 
iiflfliic Jci^cTidft on ila location, A Urgfj amount of 
it may fonn in pr»-«xitftin^ liLiroi^g tifsufn with no 
coQsetjaenl harm: but evcD a finioU scar, gitmma 
or tuborcJc in the bpaiii. or dcforniitiee cf llie iiearl 
vulvrfi whif'h follow inilamniatioDr mny 
K'Tious reeulti^ 

A pniuinc direct mo^linisical duttirl.iu ii 
10 be csined hy the innTHrial nr>tfltii*"i* in t-tnt 
Ihry cxT-'osionally accurnulate in the capillarJM of 
lh« i&titFtinf« and brum in tnoh numbers as to 




ii''ir - 


vnoinit lo virtual tbrctnlo«]». FiUrln*. vhiHi atf 
xniiltJceUukr orgimifcjii», caoM grave coaditioa» bv 
occliuion of thg lymphatic*. 

Ill disicuaiBg tli# M^ojiU coutlitiou ior th« oc^nr- 
reace of infcctiou. namely, iht obilHy ©f Uic 
inicro-orga&ifici to r^iufDa alive snd to prolifcrnU 
in Uie IioJt of tlic bo*l, Ihii fii«*t be clone with 
regard to ccrUin protective ogcncieti whidi the heat 
poflwafO t^itisi i&valing micro-or^aDtami. 

As will nppmr lal«r in more detail, Ihwe agpriHpB Ann- 
may be directed either a^inst iltt lo^c^ixs of the pnXViiii'ir.iu 
micto-OT^niniw, or ogalnrt tho paroiitie coUk 
theiiiHlve& The fcirnier re»t» in th? antitoxins 
vbicb may be pre^cpl iia the plfunia and l>mpb, 
tTKl the pover of lh« tttfuea td binO tind destroy 
tl>e toiiiu; the latt^ to Uk germicidal si^stancef 
of the body fluids (the uxelled hactcriolTeina], 
tod m thi' |»bu^ijejtif? iiml iJ<-»trLu-tiTe iitrlion of 
variooft ec!l5 of the hodv. fiftrticnUrlir liie leucocyte* 
n&d endothelial wIU. Mnnife^lh, in ArVsa] inf*e- 
tiou the mii!rii-oi{jaiLi?md arc able tu pioliferatL' in 
ipite of the preaencT of ihe%t anta^oniatie aErencie*, 
and th« condition* uhieh render thi« [xw^ibTe prnh- 
ably vafy a greet deal in diJTer«nt mft-cliow. 

Thiif, in relation lo tubc^uloeia, either the JJjJf.r^' 
Mniin of UMU and anhikala poBie^es no gefmteidnl on 
mbatnncca fur thia parlioilar organism- oi th« lat- 
ter ia roaUlant to their action, Alto^ Etncf* the 
bvcilli Hr^ frequent! V foun^ witiitr jilingocytic 
DcLU in a 5;ood state of preferTation. it wouW 
•ccm that tbay hava a ccrtaia decree of ru«ii1ane« 
to intrikceliulai di^ecticHk. Staphylococci, strepto* 
«acd and ecrtain other organidin« rt^iat de«truoiion 
br the Mrraiti, altlioufch thi^y an- nMdiJy taki-n up 
■ftrl do«tro>'«d by pliajcocvtn. ■ 

llr«4*iB««rv vf 


lie iyfMcTioy a^d tBiMVXiTY. 

Thtfl iiuufooptibiliij of tli« tuborelo baeUIu tod 
'****BrBi*m"' *'^* *^***^' menlioDwl lo the g^fiuiculnl nctioD i>f 
ttie scrum iii a nA(vr«l and conttant propert)'. Qd 
tli« olhar hand, c^ertatu urguuiimH wlijcb arc nat- 
uially aueceptiUe to th? gernkicid«1 pwcr cf tbc 
«nitn and leucocjlw appear to ac4i\ijr« a hjftirtntuv 
a^amirt tluvr h^iipIim i]urE&£ the couree of iaf«c- 
tion, and it >» n^ at all uDlikc1> that tJiiB ia a 
pTOjwrlj which U common t> all pnthouwnic micro- 
urjfttuibjiia. We nmy louk mi tliln change aa a 
plicnumctioii of adnptation. In t di&tinet Mnse it 
Sppirs tliiit ib^ mirrn-orgnniiciiifi Timv hrromc 
iinmunueil tc the bacterldtia] aubttances of the 
ftoruiD, und lo ili* opftouina on which d«ttuclion 
hy pliN^Eiiryduiiii dpprijLV 

The incTnifc of virulence in a micro-organiftm 
b> repeated pasaagt through a euilablo animal may 
ba Ttgarded 8s sn adnjitntion en thc^ port of (bo 
OTgsnicm for the ilf&m axuI Hdiiift of tJie animal. 
and in thii aditptolioxi an Lncr^^a^pd r{?*i£Uiicc to 
the gfirmit^idii} fiubritauc^ prdinhly h itn important 
factor. SiniiJar Pecnciea donbtlc^e are at work it) 
the maintcnanco of virulonoe by growing cullurep 
on miMiin which rnntAin the ^en^i of [iuijnn]». 

Typhoid bacilli which have been culttrati^ from 
the body of a patient recently are moro resistant 
to Aggiuiinaliui] than those wljioh have Iwen on 
artitkiol media for some time. Th<? snme hoe boeii 
ffiiEiii) tntp nf thfl oholeri iiibrio (PfeifTcr ami 
Kolle), aa vre!] as of eome other organisms. AIm 
the cultivation of Lacteria ftyphoid bacilli) in 
mr*i1ia whtvh iKminhi an ngglulinating serum brin^ 
about on incrtn^xi rtfliatflnoe to iip:g:lutination 
(finuBOin atLd Kilaahima, Walkoi*. Steinhardt and 
others) ; and it haft been fthown tliat »nch nioditled 

l»l«l*b«-f 14 




bficiJI) ntforb or bind Ices njr^lutioin than "nor- 
mjtr* AUHirx (Aliillt-r. Cole. Eiiivrtlji^rg). KKiitnlried 
En temifl of >^rlich's thcotj, it is a&iuined tlml 
thcT contsiti a decr^f«d numbor of i>tnding 
iiiiOi|t;cu]i!a t)T nH-f-pluri fur Utt qj:^] ll liuiii. lit-uiij an 
t^tciivc qnanlil) of Ujo luttcr i:* not boiLinI. 

B;q>«rim«nti by manj obaerveri indieatft tbst «»»u«np* 
Wfrria tnny al*Q noquirr ro«i:»tniicr to IIht bnc' i^bIub- 
Icricidfil nctiOQ cf Iho tcrum, anri tliot this pr^p- 
*Tty goes hand in hand, at kest lo fi certain evtentn 
iritli tht vinilcnc:i: of the micro-orjiuiiiam. In wmv 
of thfiw cxpcrimonU tli« rcei^tiinirc huA boon 
SfiqniTcd by growing the organisms in the corre^ 
BpendinK anti&eruiD, for a Kr«atcr ut \va» 1cn<£th 
of tirao. ThuK Colin, by growing tbtf typlioid 
bantliu on antitTpboid ^enun, conferred qd it an 
mcrcaae^ reaietoncc lo bacteriolysisr vhioh was 
retainer^ for iovoni] KubRoquont g«rtf>mtion« on agar. 
Dfly alio, in a ainiilar way, caused increased aenuu 
miiUncQ in H. proditjiotwt, B. viilganx nnd B. 
fiuorrttrriM, and cT^n rnrrEtreil %om^ piitbrrg«nir 
poivrs on th»« organiAuia, which nuturaUy are 
rath«r hinnloiB upropbyU*.* Siuh mult^ have 
bfftt cibtntflvd with the vrgSDiAaif of typlmid 
<Wiil)cer, HafTkinc and o1h«r£), cholera (S:cekely. 
Kanmra. Kila^hirua and others), dveentm' (Mar- 
shilh Knoi, Md«oo). antlirax (S!inv>', Dimyf and 
oibetiS), Ihe colon bacillufl (Hambur(^r), Vibrio 
Mftt^^niloii (MetdintkolT. Bordet and others). Tl 
h»* frequently btcn found oiso that bacteria whon 
Swtily cu1iivat(^d froir inf^^tiond have an 
miusoully hi^b n^i^Utiifi to thv barltfiddal Hi-liun 
ai fcnunn. Bctftrm ntid ^lafti ttQM thnt a Ftmin 

In lb« Ccorrfllbl, f, 3«lt1rrlv1.. He., (It. X<>. 3 



i\r^TiOX J.vr> IliMlMTY. 

<ti tlic tvflioid bttcjllne lAolatod from a "c^frier*' 

It i» Hti old t«Dr( of MdchnikofT tJiAt vinrlcnt 
micro-orffimlflma arc lc» Efudcvftible to phogocvlo- 
sU ihflD aiirul^nt. Hiid wu suppoeed to he due 
ti> ttii' ivtJiMnLhmrtit nf n nr^iLtivr cVmoliiK]*, 
uliidi coiuiatcd eillicr in ■ rej>dlijig of tbe letico- 
cytdft or ia tbeir fiilnro to be a1tradt:d to tlie bae- 
lerla. la 18SS Maaurt r«portc^ tlmt Ipiicofylps 
were ncfiKtirc chcrnoUcticaU/ to vimleot iitraitiA of 
th9 orgoniena of untJirui, chtckon c^hobri^ swiiu 
pjagui^^ and to fi. pjroc^Gnru^ and Ti^nn Tnrf<;AHt* 
l-ovi, nnd tltnt tbcv ^\'cn: tak&Q up by l«ucocytc» ia 
thu snlmjil «:tpc>-rimrtit to n much Irnc «Ttj*nt t1i4ii 
avimltnt. liUainB of thv same organisms. The tome 
condition waa noted in relation <o etaphvlococci 
(viiTi (Tcr Vdclr, KorW, Tavnl). Since phagijcv- 
tO«U lioB bem studied more erteniively nndcT nrti- 
fidfll conditions, the ume phenomenon baa beoQ 
noted iu rcluUon (o otbcr orgnniFms, as the Btrtpto* 
C0MU3 {Hcktocn nnd Ittiediger^ Bordct, ctcO* 
pneumococcus (Hosenov), typhoiil nnd parflly- 
plioid linciili (Neuft'ld njid Iliinc. Hekloen), the 
polon bacilhis (Bentlic), :hk? meningococcus (Flex- 
tier), and oilier^. In African liek ferer, Tivvadltl 
and Roch^ noted tlie presence of spinlUcidil and 
opaonic «ubEtnnoe£ (lho€? fsvoring ;»hngocTtot;i9) 
following the firM. nttuck of fever, bnl lliev 
appeared to be effeclive oci> on iJie ipirilla vhidi 
wtre present in the blood during the flr«t attnek. 
Bv tbe time tbe second attack occurred the organ- 
ifcmB had acquired n rt^^i^tanco to thc^e gubBtnncc? 
ttbich they n-tiMiu-d during wvernt pnPSJiKt^s 
through rata Piib«<^nently. It n^oiild Bcem that 
thla fteqnfr«d r«fiifitance cit the part of the or^nn- 

j^sjsTAxcis to nuins. 


thai thU mig^t go Jndefinit«1\ n^rc it nol that Uiif 
ho»l evrjilually rcsponJd ly llie ^roductloQ of 
BU<^ 4 quantity of ^Ecnnic^diil subfituiKt* tlmt ihc 

that the con<litioi30 are not v<!ry diiFertnt in &.vph 
Ui« aod in nomc of the ehrctio prota^coic infcctioaa. 
BC ttypsaoMiniinFii' 8ni1 jiirpplrunioKi* ; in sll thcM? 
dieaaea tpecillc entibodic^ av^e pr^^iuccd dunnc tho 
ccuna ol iiif«ctioii, niid tlitre is good reason lo 
Mieve that eomc of these arc germicidal ia charac- 
ter. Thia i« certaJDiy tnic in r«^rd to pimpliumo- 
fcU and lT}'panci4r>n]i«!iiB, }'et Hie orgnniMiis p^r^iat 
in the blood nnd tisjttc^ uf the ho»t lor a lunjc 
|>oHod. It eeema that they miifit hnv^ bnromn 
adapted to die jir«»enctf of the^ ^ennlddul «ub- 
atflnccf. That virul{^ncc it not toat aa a C!ODaui]iicii«c 
of tMt adaptdtinn U «hoarn by the fnrt thnt tho 
fclood when it is injected into a fre«h animal repro- 
diieci a tTpi(!al ucutc uttuck. 

It ia Dotcirorlhy that n similar re*itlanre to I'pr- a«4«Ip«4 
lain drugs can be induced in trypano^omcji when riTD"""' 
iiifKt«1 animnla arc ^\nn repeated injection* of 
tJiwe (ireparatonif. If a Biifncient *^«iintity of one 
of t^Qfe drugs (tlox^l, furhsin, try|)an-red. etc.) 
ia j^\tn lo aa infected tinimal, a complete cure, 
*ith ilmli^tlon of thtr bodv, may be obtained, In 
(he eient, however, thai an iiiM;ffinnnt (lunutity 
o( the druf- ia adminiatered, the or^jantema when 
injcdej into a fti]h«c>r[itcnt antnifil may be entirely 
ifidiiTercnt to the picsoni'c of the druit, which^ con- 
teqnencly, has lost it^ therapeutic value against 
this Btrain. It ntiiy In- rirttiamnr iv rej>e4t lliU 
proccfS through many pAMn^ea before a hi^h decree 
of drag reitBtanoe is ohtain^l, hut when once ^Uh- 



liibod it U ot lODg durotiuD. Such Btraiiu «ro 
cnll«d 'VhcmofBftistaiit/' It lins bI»o b&an fhown 
that trypanoKiniea ftcquirc a reeifitAncc to tli« 
gerniicidal pmptrtivK of servm, as io Wk cai^ of 


in view of tiie fact tbst some micro<or£«nijm« 
|jro(lii4^ it vii^8\i]t wlrHii gro^vn tn ihe animal bodv, 
trhcr'NiA it is nlj»cnt iti ordtnor^ culture media, it 
has b^n Kiippc«e<1 bv vonit that fb« cnp«n1e in an 
uxpit^sruu uf aJaptalioik on the pari of tbe or^un- 
Uia 10 tbp ;;cmitL'idnl a^'cuc-io^ of tlic boet, that U 
lA |>«rbupg p'olrt'tivR m iU i^lmrachfr. Sut^ 
DbaervatioiiA have bccD made in rdation to tht 
antbrax tiactlLua (DciitBOh and otbera), the itrep* 
tnc'ot'iim (BiHvlrt^ MBrHmnd Jiud oUn-r's), anil Uitf 
pia^c bocillas (Ijcbkin)-' Thin Mahonf^bip, how- 
over. Is not general, and can hardly be considered 
ns UiorciUgUly usiablialied. 

In addition to thit more or lou pauivc adapta- 
tiurt oil tbv part of niino-nrgnni^infl. tliem i* ri^n- 
.lon to be[]eve tEjat tlicy may actually antagonis^t 
llie prol(?Ptive ageades of tbn body. partWIarly 
the |irooeai* of phflgopvtoais- Arloing and Oonr- 
moiit. and Hogor believed that baHena Bporoto eiib- 
sluncra which fiivia- llioir grottlh in the body, 
Kogcr obBWTTrd that iin extract of iUft bacillua of 
pymptornatic iinthrax when injeciGri into ihn rabbit 
favored infection with tlii& orgfinltm. Bouchard 
apokt <tt euch cicnicnta as substaiufs favcmatitcs, 
Knwt* (KrifjJi'r'tt Brjtmyt, kii, il39) wUo ht^lievtid 
tliot such mbstaiicw oxint and cnlifd them collect- 
ively ItitMie SuAtaniPn, Ant^nffRtoffe^ fidsrLy$infi. 
He supposed that their effect was chiefly to rmu- 
tniliio Ibe alcsine, Uio name vhicK at Ihat lime. 

3. CUta bj ^liertbfir^. [ «. 





lA-jt^ applM to tbe bnctericida] siibstanceii cf the 
rarum. T}ieir o\i»teiicv had uu iatisfncttjrjr nip- 
port at that limo. 

A UttJe later van d»r V«1(lc dii«ovca<<l that L*Ba4>«iiiiii. 
rtaphyJocooci tecrrit a &uljAtaiii\^ wEiioli la to\ic for 
l«tiM)cyte«, tbc so-CDltctl ^rur<j<-ii/irf. It appcavc^l to 
he |>roduced by strains of both high and low viru- 
lence. Still mort' iix^ntly il was clif<(^vcrcil that 
tbo atroptococ^tta producer a toKin which in 
dtstractlve for leuooevti>^ (Pue^iger, Bearedlca). 
Tliew rvsuIU Augge^t that a Ioaig action on the 
lnuoCTt» inaj be a factor for Uie progrtM of 
mfection, and mur ctpUin, at kii«t in fmrt. the 
mutance whldi virulent organiftiiia thov t^wanl 
phajfoeytoritd. A ponioulorly fif-uilionut obeorva- 
tion ia Ihjit hj Kitf^niow, tn tlir rfTivl thril v^rulejit 
pwaiuococci accrete a anb&tance which has the 
power of inhibiting; ])haj;ocytciia, a aubataneo to 
which the njimc of riiuliu va* jfivitn. Viniltn cnii vimiiik, 
b« oitracti^ from nmlent oiiltiiri.** by m^nn? of 
isit aoInCion^ and after ihi^ haa taken pljice xhe 
€OCd have become »ii»ccptiblc to phnj^ntcai:!- Alao 
after avirnknt Rtrninfi hare boon tr^t^td with the 
»tracte<1 vinilin. and lat^r eeparflfed from it hj 
vubiiifr^ i\ity are found t« liavc acqiiir^l rc^iat- * 

BIIC4 lo pliagooytosin, Kia^nbcrg also obiEcrved that 
leDCOtoaic fiib«tanc&s are produced by the bacilli of 
ayraptcmatic anth^a^ and n)flli;;naEt edema. He 
furthermore bellev^^ tluit It \h a rn4>re or le«a ironi- 
mon property of bodfria to produce mch anb- 
atanoea id the conne of infection, although they 
fo^y not be obtain*^ uudf^r artifu-iat trcMiditiurid. 
and that they arc idenltml with the '^ftiyrrcwiinpt'' 
of Bail. The corrpome** of ihts Wi^f, howev^, 
ii Dot fullr deuionii traced. 


ixFKvriojt xnB luvvyjry. 



ddfll ftubAt<nc«3 of the eenim for Diitufal immnn- 
ity, OJuigniE lo phagocytosis iho OMfiitinl tMp, and 
believes tltat the iiruJL'UL'C of Uji? };!i(abLl4^ d^p^mls 
on tbeir jxiwer to j^roduce ^abstancctf, the nggrcs- 
iiiris, wliirti fiiitH^u[ii;ce the prtH'CJUi nf pbji^t-ytoHl^ 
The A^r«aaiDfl were euppo^d to be Qon-toxic snb- 
itfincoii whieh were proclu<i:'d only in the body of 
lht< iiifiTtM onimnL VIlch llir or^nnisma of 
typhoid, c^holcra, tubcrculo«ie bud other diaeace^ 
nre injected intmperltorieally into the guinea-^lg, 
tlie a^igrewtiift appear hi the inHanimataiy <±xadat«r 
»nd are ohtnined free from M'rxng micro-gr^niMTW 
liv centrJfugnlion ant] siihse^jueiit cheinical pterili- 
Xdtion of the o^crlyinff fluid. Tliin fluid, when 
mixofl with tli^ homoiogOLifl culttirn^ ha^ th« powor 
of rendering fatal a quantity of tie culture vMcb 
otborwifle wvuld be unc^lo to produce infcctioD, 
und ihti mtvtitri' may cnrsc n v^ry aeiite dcuith of 
the Gxpcrimtnt animal. Dai] found all the more 
justifies tion for aeeumin]^ the existonoo of this new 
(?) subatimce iwtn ihv fa<.'t that irutn[ini/-rttiim 
witli the affgni^sina gir^ rise to a pcmm which 
hoB llio power of neutralizing the effect of the 

* IggriT^aive rxudnt^; hence eucli a ?ct\iin wuvlrnnrd 

an aniiacgr^isin. 

OM»vUrtihm. The FttidiQ« of othors^ howorar (WnA^rmAnn and 
Citron, Docn'. Sniieiberk atid others) iiidii-Mtv Miat 
the nggrenins of Hail do not represent a new entity. 
Wuiermann And Citron found that the ''a^gres- 
e^nii" as prepared hy Hail are tovip, nnd thnt they 
may he obtAinci^ in nrtifiniDl cnUnres an well as in 
the body of an animoh They probably represent 
notlun^f more tliari the ryloplasm of dissolved bsC' 
teno which may exert nn inliibitinj; ctTect on phi- 

AD^PT-iTioy OP omsM^^is. 



goc)~tc»f in jtiovt! thxct mir vmy. The iniic 
pohrioncee mft; injure tlie Icucoci-tcs to nich an 
extent that they do not readily talze up the livJog 
OTginwiM; nncn Ibvj rf:pr(«i^iii diEiiilFgratcEl 
orgtoians. they mftv, like the latter, Abaorb or 
*n>illd'' tJ]« opfioniiiB cf tbe plains, on nhieli 
|'!»gocJt<ls]^ i3('pO-ii{l:(, nm] ilum frrcvcril Itit nclion 
of ttiG opeonins on th& bnctorial celU; similarly, 
l))«y hi&d tlie bact^olvsiiiK of the tifnmi. ntii3 
hence dircrt their action from thr 1ivin£ cclU; 
a]«io, ffiDCO the dt<»oh«d orgiinUms atp toxic, when 
Uie "aggreftsine'^ art* added ti> Itvitig L'uUtir^, the 
total toxicity for the antmnl 19 incrvjHpd by ju«t 
tliat tntich, Th«r^ ia sIbo evUiencB fo nhov that the 
mwt indifTfrftil pTufvld auhtlaijrcH \tlit'ii lujecti^Ll 
into ID juiima! nmy ilt'cieoee its ri>s?stui]Cc to infeo- 
tion nr iiif/Jtioatinn for lb* tnompnt Thus tfirk 
etta and Kirk found that a irnoW i^uantity of egg 
ftlbumb, broth, or ocimal serumi (^At, guinea- 
pig) when injorl^'r! into white mioe, i^crrrnse \hv 
twifttflDCe of the latter to a concoriiitflnt inocula- 
tion vith t«tanua toiin. Tho foreign gub§taiiotH 
were ■upposni lo pre-engage the absorplivc auii 
dtgoetivo powcra of varioLis eeJIa (l^ucocyteg. etc.). 
BO tlutl t}ie lo\in ikDB rl[F4|iLj4e(] rf lets rt^Hdlty^ anri 
more remained avaifnlile for the highly RU^ccptihlc 
Dttrvova tiwnw. 

Ttie ramnrkft Jtict made ttTfi not rrtprrfiH! to eart 
doubt on the pn^Uililitj thul putfioj^rrtia rnlirro* 
crf^aDifiins produce aubstancoE ^4iidi aro antaj;o- 
nietic to phagooyto«J*. That tho latter action 
really occuw baa already been lntlicat«d. 

Id previous para^rrapb} fitti?ntioii vtib callcc) to Hr«i>uiiir 
Ibe fact ihnt niierO'urf^oiamp at1yin|]t to adapt tVeSSIiT"*' 
tbrmwirn* to thHr Wt*, to thp md thai the latter 


nrBcT^os A%'D tMMvyny. 

A 4m 



fiMf be a mora ftiwcrMe modiiiBi f^r tiMtr exist- 
ence. Thnf> they iscrMM in virulentv, aiul dlstnn 
tbe bMt by bccomiti;; reaidUnt to tu protective 
^endci, ind cfcit icrtivoly anUgODiEo tha UU«r, 
jMirtJcnlarlv at rvgirdi plis^ot\to«»» and by vudi 
meana Ibe lutnral iiumuTiity of tlic ho«t la r«fldered 
inrflV-ifnt. The hout, howtvtp, u not without iU 
ovm revcrre forces, and. in faron^e t$»ah tfter 
infection is once ffilabUilied. h rcsponda to tke piw- 
ciiiv uf Uic i[iiL*ru-ur^ai]iMii9i by tlie jiniduclian of 
A IK^ supply of protcctiTe "anhbodic? " Umj cfftc* 
of vlijcb H to d«Gtroy larger Dunoberfl of tbe invad- 
iu;; orKaiiiBiiiitr or rvrfiii to bCerilixc tbe bodj com- 
plrt*^W, In Iho Iflit«r caao fwovwy ie tho pwb- 
nbl« Pivnt Thi«, flg«in> may be look^ on as a 
process of ad&ptatioit ou the i>art of tbc Hori, in 
wbioh It «Mk« to d«ltroy or r«n^er lest iifitiou* th« 

Jn ixrtQJn chronic infections it pccma that a 
mutual adaplatioD tak«« place, to that there la a 
ti^ndrni'y U*t ttip htwl nni) purasitif to ]]\e in a half- 
way ntate of Iianiiony. Tbue, in the acute stage 
of FVphili*, tbo "combat" botween the hort and the 
«pirot*)i('t<*a if nil nflivi* ont*- EvMituallj, however, 
it ^voHld wcm that the hort reacts by the produc- 
tion of prolectM't ontibotjiee^ a condition which 
i-raulu in an Hrndioratiuii uf ihv nyrnpl^tHs. Stoce 
the micro- orj(annm« n\ny rcmnm nhrc ond virtx- 
lent in the host for s long time nft^r this he? 
occurred, it appear* thai Ihty bwume habituated 
to the prceC'm'O oi tJic ontibodicn, while the hort 
at the wiTiie time lipcrimp*, hnbitiiateil to tlie tnvirity 
of the »pirocht1c0. After tiie lapac of ttill further 
tiroc tlic adaptaticn on the p^rt of the patient 
appears to Incrcair, and tlio micro-organism also 




loses Jn virulcnc^r if vrc imr juJ^c from the lonr 
iDfectitity ttfuull^' accredit^ to UHiary Ic^ion^ 
in ipilc of ll)e fact tliat Ihey conluiii the splra- 
dieCO^ Tbu mutual adaptation^ bowcrer, docs not 
lOOtD Ifatt tiift liCBt c«cxp«« iDJury w a con«9t|uiincc 
of tbe infection- Siutilar coD^Jittoiu probablj pre- 
Tatl in piropls^moiis and tlTpano&ontinaitf. or o^c^ 
in relaiwiiig f*-T^, oa cuggMtAd pn-vjoitKlr. 

Wliat Jiaa conie to In* knova as the liypotlasi^ of 
Welch mtv be meutioned in tliia <x)mtectioii. It 
may bp put in iUv fL>tTn of t1i« follnwitig f|Ui>itiDii: 
If bacterial toxina and tbc coDfititnent^ of bflctorial 
odli 00 a«t en the tiwuc celJs that the latter pro- 
due* bodies (antiboilifs) nhinli iin^ iuiminjl to Ibc 
bttct«ria, why mav not tbc bodj tluid« in turn so 
act on the bacteria that the latter produce bodiea 
(■ntibodin) which arc iniinifal to the tie«u« cclb? 
"Lookad at from Hie point of ri^w of tl^a hac?- 
lerium^ aa woTI Ji3 from thjil of the ai^iinal }io^t. 
ac«ofdinjc to lie hypotUefli^ advanced^ the stru^cle 
bcttfoen tlf« bacteria and tlie bodj ecUa in infoc- 
iicaiA nio) he conceived as an immunizing coDtest 
in which each participant is etimulated by lU 
oppoTiefit to the firoduHion of C}1r>to»Snii hodtiln 
to the other, and thcTcb.^ cndearor* to make itself 
joimune nj^amtt iu aniagontct" (Wdeh). 

T7«Ht ba^'teria ninv af<]«ire incrent^l rp^icinupp 
io the distructire *£cnci« of the ho*t vim rrfcrrcil JJ*,'"^^ 
to abore: but Ihc liTp>tlici')g of Welch iticanr a 
$ttMl deul more llutn tlio imnnmiuition i>f tl\c bac- 
tcna n^inrt tJie dcfcni^vc povrent of the animal 
body. Xol ooty may a bact^rinTn dtirinj^ an infeC' 
tioii U-outne mon^ reiiatujil to ihv hui-d^Eicidal 
ootion of the body by producicx antibodies to thocc 
bacteriri<lal i^encj^fi. or by iit ability t'> ab4nrb 




tyi'^ECTJOX A^•D ill^VSlTY. 

and difipase of ft greater quantity of bact^riolv^iit 
or opsonin; nud uot oiily uiay a bacterium be able 
to rctpond to ihts pr»c:)t;o of naluml an1itoxiti« In 
th? boHy hy the prDEliirtind of mure toxin, llie 
isecurrrnce of wliich under artiGcioJ conditioni voe 
ffiown bj Woehsb^Tg In relation to tiie diphtheria 
bndllui; but, in addition, certoin conUitnt.'itlff of 
mir hody fluids ma_v^ by oorabiaing with auiUblc 
baclt^rjal reteptcTs, stfmnlate (he bafterium to tlio 
pro<luctiOD of n whole shower of c.vtotoiiiw, whidi 
ntta^^k tho Jm]CD<^3'(c«, ^tjthrocytPE, nftrvo caIIc, 
liver, liidoej, etc. Tlif nature nf tht* Animal tiih- 
dtancis whidi mikv combtnt with the hactcrial 
rPEM-fiti^n: mid thus cniisr^ llur foririiilion of thr hwi'- 
tcriogenic cytotoxint is Jefl an open <iiie.*tion and 
ifl not of ^aeential importanco to tho theory; it la 
uol ui all liLveMnrv Ibat tbev hi- iux'n: lo tho baC' 
terium, anil thrr iriny rv«j bo inkc.n np oa food 
Biibrtnncfs. I.ik*?wi8e the powible nature of the 
c^vtotDxlm* proditcfd by the bacterium la of et^ond- 
Qiy imporUDce. It eo liappurcd that AVdcli 
n wn mccl thnt ttipj' might he of ihe nutore nf nmbo* 
ceptOTs v'hich umy be complemented bv bacterial 
compIcmcTit, hv th« ciruulatjng complement of tho 
body or by endocomplementa of the tissue cpMr. 
One rould with cqiial rcHflonabJeneas nssiime that 
thev mny be complete toxinf, receptura i>f tho e?c- 
uiiiT onli^Fj wUh BL hdpLopboToii» and a toxophoiiiu!* 

In Bomo support of this general hypothoeje is the 
observation that the gtrongeat leucocJdin (a toxin 
for leucocytes) can be oHninird from the jtaphylo- 
coccuft by moculating thifi organiMn into a GerxniB 
cavity of animals, tlie toxin being obtaiued snbee- 
lucntly from the inixtLire of cocci and leucaryte*' 

AVKKf^tc t^strxtrr. 



jJlAvc not AdvaDccd far toward thu 
inAtioti or tliij coir«ct£i«w of the 

In EJirlkli's conception of "ntrcptio" inmiunily, 
th« poMibilit^' h eateruiiied tbul mitrn'tirgjiiiiRnui 
«omcti£D«« mny not be able to jEraw lb e, Iioat 
b«eanM the nntntivtf conditions an; not tullftble^ 
It probably wou\t\ be grauled dint proper niitritivi; 
rabaUnccji arc |>ro*cnt in Uic host, but it is afeumod 
that tli^ raay be fi<y iritimittvly uud Unnly Uouiid 
to olliex tia«ue ctmfltitu^nts tbat they nrc ngt Atail* 
able to tbo micro-organifims aa fooii. Virulent 
inicro-orgautLiinia find Uie nutriiiv« stibsUnces 
already nmlahSc. or^ li thiit is not the couditiou, 
tiM injury vrhirh tht?y eflK^t on ihv iUm^fi in tlio 
firei uutance tteults in a spUtlinfe' of tlit coa- 
Mitucnta >o that lit^ food lubetaoco (rather a ape 
c'tdc fond tLubsctiinci') b^vnmiTK nvnibiblE*, Avindi-nt 
or^nni^nas not having the power to produce ihi* 
splitting refctilt do not proliferate^ to any groat 
ilqgm ftud Kcon liecoiiie tbi- ptEv of t1it protective 
ajcencicfl, mirh at the leucon-te^ and ba fieri olyains. 
With this theory m mind, one refurfi tn i\w 
^^exbftiution" Uieory of iuimiinitx at oue time 
QOlertal&«d by I'biteur, and oitod in n piL-vjoui; 
ciMpter. Thin diffrn'ruc nppvflr*. however, thnt in 
Fisteir'a theory nn entire Absence of suitable food 
v«A aaaumed, whereas in ilic atreprie theory Iho 
food rabalano!^ may be prei^cnt hut not avniljihir for 
tlw vm of the DTgam»ni'. The atreptic theory is 
put fornard a« being n possible factor In reAUtanev 
to wme infections by *ome liofta. not, of courw, a^ 
n theory lnti>Tided lo iu]»pbnt otiior gieneral 
tlrtone« of ininianity. 




By itnmnitity we understniit) that conditio in 
vhich iin iniHvtilvifll or n ^pf^cs of AniniQE tT^lub' 
ila tiDiiBual or complete resistance to an mfectioc 
for winch other indiviiuals or other ap€cies show 
a gTflfltor or loes dogTCO of susc^tibilitv. Immune 
i'j from the Latin tmMtjjiij, which originally ap- 
plied to one who vas cscmpt frotn h j>ublir aervice. 
fixempt from tribute, or free. Although the word 
i^tilined thi* ci^il mt^aning for fentiiries, and still 
retains it in certain connections, it al»o had, even 
in anai^nt timee, a limited application lo the pro- 
tection which HB individual might posses?; ugalnst 
poieona. It le seen, for eiampla. in dcacriptiona 
ol a tribe inhabiting Nortliern Africa, tho Paylll, 
whrj rtcrc said \i\ jjo^tip^ a ijiii.urnl immunity to tht 
bitcfl of poisctuous snokev, AlUiouf-h we may be 
pertain from Ihis oitd ulUi>r i-(*fer«DCi>« Uiat o con- 
dition of immiuiitj- ivna recognised in Tcry ancieot 
timo«, thfl present tignificanoe of the term has 
develnpeil hrrgely from a bt-ller iniderstflnrling of 
the nature of infectious diten^^ and of the condi- 
iroTj* upon ivliich the rcsietnnco of the body de- 
i»i>pa«*« Aa tlie dafinitioa pu*:ffests. \Ye <lo not think of 
tmiininiir^ itTtmuntty to such procesBea t^ Bnghts dideasSj 
artevinsclorcffiw or f.h? inMaholic difleaaes h^"i '^nlv 



to lh<k«p wbirh we bave Jearneii ta tecoguiEe aa 
iDfootiooA, Th« fact tlifit ao indiTidiial id fre« 
huRi gout, ctmbcrUji or any other rnrUbultc diAliirb- 
tLikoCt cooaot he UkcD £f indiciiting ah ^mniunitj 
from tfaev disoae«e. Inaemucl as the mctal>o]ic 
dueaaee appear lo depend uu Uje i^im* i>f ctirLiuii 
ovguu to pCTform Uieir lonctiona nonnaliy, for 
aome one <ir more rcjirt^riH, wt («d onlv Jtifrr that 
in ihote ^Jlo ak ficc from »ucb diccatcs the cj>rrC' 
fpondiag orgaitE fir« in b etaU of normal activity. 
Similarly au judiviiluaL or tnttt ^hLdi is free froui 
All mferiioua diivaflfi bcciiuBc of lack of opportun- 
1^ to rontriit^t it wonld not Si? clns^d &$ immune, 

Imtnunliy has no necdttttry reUtion^hip to tha 
d«sr«c of coot&gioiiniCM of an infcclioiis disease. 
although aajuQ of the moat itrikiog iLnd certainly 
the rootft cxinimoQ e^iuutples of imwuiuty are socn 
in relation to eueh inftfctions (as gcarlot f^ver and 
smallpox). TctttnuF, on the ottiei- Imiid, wlucli is 
ab^oTnuly noB-contagione, can lik«wiflo ^vo rise 
to a high degree of imciiiiiity, 

No mt^lJcal fact k more widely known amfing Aflanir^a 
i&teUigeat peopio than that an attack of certain i"a»>«BitF- 
of ottr iiLf«ctiou» diseases brings about lomc kind 
of chaiigs in Uk; piili.cut*s tissues vrhicli proti*GtjL 
bin, or rendcTS him immnne, against further at- 
tackt of the aame disease. rnnamncT^ a* ho van 
prenonalj snsceptibie, the new property ia nn ac- 
quirad one. sod bo is nov nid to posfict* an ai> 
qoir^ immuQitj agaii»t thie infrctton. 

Tt in aNri wdl known tftul. many diKL^nft^^ vh'tcU xmi^wx 
attack man con rot be inoculated into nnimale» immBntiT. 
anH htologwtn are familiar with many examples 
of unmnnity trhkh are coaHnet] lo particular spe- 
cfoa. The lover animals apparently can rot bo in- 




feeted with Actrlei fever i>r tii«u1«. nor man with 
diEekcn cholera. The nvj^Q U Ion nuoeptibic 
tJiui th« vliito naaji to jellow fcrer. The rGmfit- 
aiice vUich tl]«^ eiample^ Ulu&trati^ e^LJsU itotur- 
oity, DCft throngh bnrir^ die disease ; it is a nntuml 

Natural immunity iia, for th« moft |>artr an In- 
licritcd condition; Uiis ceitaioly is the c«w vbcre 
ft vholo ckcja of aDimoli; is im^olvod. Similarljr, 
thu Kusce|jtibiliiy wliioli i» peculiar U> a species 
muat be horcditai^-. It ia often aaid of some dJs- 
efl»«a that Ihey "niE in familiM;'* e. g., oan-naoma, 
£out, tn»anit}\ ThU appears to be ja£t ae true of 
aomc infectious cSisco^os. 1I:o icoet tiot«worUiy ex- 
nmple flT wliich iH probjihly tuhcrfuiosis. In con' 
IraAt Lo Uiia inherit^ vusceptibilit^ is on iiihcriicd 
Immunity, which may also "run in fainilieH." Ji ia 
not *o <<Ji>y to ndiJucL! eiamplee of Unx We are m 
tho habit of tlunkinf^ of the individual vha can 
resist nil infiWintjH ns repi-p*enting; a sfanjiard. 
He. 'however, ia above the average in reaietance, 
and tlie averairn i« out proper itandard for «li- 
matiug the rcyiiftUnt-c of a «pccic» or riu*B of ani* 
mala. It ia iindonbto>it)y tmo that ^mo fomUies 
poeseM an irnusual reaUlanoe to tub^rculoais- 
Piirthermore, expcrimcntnl vrork with iuiimaU ha* 
proved thaf^ vitliin limit*, an immunilr to cer- 
tain infcciionM (t, £., tatanna) ncquiit^ by a fe- 
mfllo may bo tronemitted to lier offapnng. Sitch 
im)tnii)ity, houever, h very 1ranfti<*Dt in cTiametoTr 
tin*} ifi "pftwive" in ita type; it dopefj*!* on the 
Irnnbier of prolcf^tive ctibMcncvfi from tljo circula- 
tion of the female parent Eo that of \he eirihrjo 
irt utero, and ^ome w&eks after the birlb of the lat- 
ter tliet* aijbi^laneeA aie eTimiiinti^d and th? immim- 




ily dtfAp|Mtn- Tlmt of tho parent, lioHcvor, [wr- 
mis for & xaxKh longer period; it it *'actiT«" in 
titrtcc^p *« explained Utor, Even in a g|«on 
funiljr, ItoitrvrT, Ihen arr cirieii tiurki^l vaiiatiouA 
ia snaoeptibiUty and rcf^ijitAncc, One fbtld m ft 
ttmllj may coittTACt vcnrlet fer^r, wMn anotberr 
living uDiier cjiadly the Mme conditiom, mty 
•scflpo it. 

SuMcptibitity mlno ijc ofUtu OL^uired iei a more 
^ Jan etincscc^t nny. The rc^irtancc of an indi- 
vidual Ezkdy VftTj gTiatly at diSerent timoe And 
under difT^rent t^omlitioin, Tlie^^ ere acnd^DUl, 
acquired «bi(cft ^cli iu> may bu (xrcasioned by 
BXiMiattion, hting^r, ^vpotwre to cc\t\ nnd oth»-r 
unhj^ienlc coiiUitiona, 

Bcocntlya Uic cxifltcncc of n Tt;>oeiIic acquired Acasiref *■ 
fOiceptiljilitj to vanouft prcteid cnbRtsme^ sm) 
bicierial [jioducte \\At Wii determined by ^jiperl- 
nicniaijon. An injci^ticiL of icrum or vurioua pro* 
Indc into tlip prni^pc nniiiin] rfrmtf^n it utTrmnly 
tiuoeptibb to a accc^nd iujocLion; and a person 
»bo U ftilTering (rom a parUeiiUr fnfet^tioQ bIcow* 
nmmiAl wn>Mti\vnc»« to thv prodncte of the orgtu- ' 
lem Qiucitig Ue infoction, u iLown by tho tubcr- 
evltn reurtlon of Kocb. 3uc)i anlmali^ and indi- 
ridnalt arc Mid to TtaTc been <i£nji/i;^'/. Tliia sub- 
|*<i will b« ii^«ciiep(^d lator iindur ^'Anaphylaxis'* 

Mitnj of these tacU were familiar long before 
■tnjllitnf; wait knovn regarding the principle on 
nhicfa tlwy depend. SubAoqueut to tho diaoovery 
of iome of th«B pHnriplra (to bo rrtmidRrwl 
laticr), tt became convenient and neccwary to rec- 
otptam otJiOT jtpcdo] typci of immunity, although 
any typ« which coc hv conceived mint utill Rnd a 
place under tither Datura! or ncqnirod immunity. 


tsFKvrwy Asit i^uuMtrit, 



AhlioLigh fiut^h (IJ^Mfs as typbmd And choleni 
arc accotnpnnicd by pronouDced toiio bTmptonis* 
ttie poiionoua subfitnnc** mwm to ho inU^grilly ae- 
sooijihHl with tlie bjicteridl protopla^zn and not 
lecreted In a eolublc or diffimiblc forn) by Uio U»- 
ing coll; they nre spoken of aa iatracellulflr toxin* 
or endotoxins. CHiteivationa point tJj tlie Wief 
tliat the ondotoTciru are ]ii>crntcd only after tbe 
boctATiA ctre killed and difsolvcd. When <me, 
throngTi inf^tion, bu* urquirt'd immuoity to ty- 
phoid or cholera, his fresh f^rum ia able to kill Uie 
rospoctive bacterium, but apparently is not ablo to 
neutraUw its loiic snbetance. Hence, on the ha'iU 
of the nature of the sfrum, iEumnnity to such dla- 
cuAOa la 6pok«n of &^ Antibactonai rather than 
nnti toxic. 

Although the 6ub]«ot h siH] in a derelopmenfal 
*tnl(\ the cotidftinns Jiidicatf thni th*jrc nic two 
faetom m aritihactoi-iul immututv one in which 
tho plaama or serum hae .a mafb^d power of kill- 
ing thf- mirfni'iir^uniKins, t!ii' uHiP]" in which llie 
destruction ia largely by means of phagocytic cells, 
Tho former wn^ jn^t wffirred to. Both og^n<?ief 
o[>eralo in many infections, as in typhoid, dioWu 
and other*; whcrcM in other iripitftnces (»trcpto- 
coeci, tstaphylot'occj ) phapacytoeL- is the only dc- 
t«Giabl« prot«ctivfl sg^iicy. In mo^t oa*efi pbngo- 
cyto»ifi runnot take plncfr until crrtain conititucntl 
(opsonins) in tlic plfL^ma or eorum have ''aonsi- 
tiifod" the bncterln. In ctto of recovery ihc power 
of phagocytic destruction is Tiauallv enhnnccd. We 
hove, tliorefort'. to rccopnistc phagoc^'tie iiumunily 
ru lypfl, '^r at lea*t as an importflut factor, in 
both II itiirnl nnd acquired rui^Unce. 

AXTSTOXW fifjjr.v/Tr. 


In conlnil to inffdiona of the tvpc rcfcncd to 
AbOT6 art olh«» in %'hich tlic f^mptome arc pro- 
duced hf M>liiM(7 toKJiLi, the ctjtntoxinfr which nre 
wcr«ied by Hw nijcio-orgftnum«. 

The *rmptom* which aTfl so charnc-loriGlic oi 
UtauvH an- jiKiduceil, not lij conlacl of the bactt^ria 
vith the ntrroud »j«1einf but ra^«r Ihroujfh lh« 
•p^cifJ^ foltibT« twn which U iM-rcInl by t-ho liadUi 
m tl* wound wh*-re ihcv retide. 'VhU poisoiif cr 
U>xujf Id oamc^ from Uio wound l<* the nervous 
«t«trni through (hr lymjihntir of bloijfi < iri-Llatiun^ 
Ibe bacterlDm itself not being trnnnportcd. Thcr^ 
fore, alUiotigh tctAttit is & bAdoTisl dia^ago, it it 
at fhc Mine timr aud in d p^tujlmr tttmt a loxic 
dkSGlMC. The pcram of nn nnimfll ivhich hnn 
3ic<5tifr*d kinmiinifjr to iliphtheria or tetaniiH npu- 
tmlino tii« corrc-0ponf]inj; eolt^ble toxin, but (l<>t» 
not ncccsMrilj tnjuro tlio miero-or^fiiniifm iU«ir. 
Tliat i> to tav. the imnnmily Is antitoxic. 

Eipcnence ha* diouu that OiIh diHtindjon 
b«tw«r>o untibnoloHal otid nntUoxic iTnirumty in 
an im|>ortsnr Qnt^^ an*! th*» iliJT^^rpntijition i* »ery 
^harp in tfntic InHtanccft, pai-tlculuily lu acquired 
ImnitmUy. In many oamiilt.'* of nnturn! immiin- 
i^, tUp rcjfttnnre cotinol ho nttribiifocl sa spcciflc- 
•liy to an|ibfl^ti?nfil or ojititoiic acnim properties. 
This ii r«ferrod 1o later. 

In tlie ijijet of iamuinily nft-rrwl to, ihi* fuC' 
ton oa vhich the mivtancc <ippc^ars to dcpeni;!. 
1. 9y the germicidal cr antitoric adion of the 
fenun or the gennifidBl |jorter of lit IfutiH'vti?*- 
trt ntecptiblo to experimental dcmoi;!: I ration. We 
■r* faiTtilinr with »nnt}iw tjpp r\t rpui*fiince. how- 
«ver. ffitich find* no eiprcsAion in Uw form of 
antitoitm or other antiltudlec. Thii: roUtei par- 



jxfuvTioy ASD tykuyiTT. 




ticulwly tc b&bituatiOEi to various ^rugr, ob mor- 
phin, cochin or urscric, to vhich a high miatmicr 
mtiy bo bcqiiirod. Tho Inie explanation of fudi 
rpuEtJtnf^r^ i< nnt knovn. but tt troiild appear la 
depend on fioutc acqui«d property bj tlie cell* 
whioli wei'e ori^allj more susceptible; in other 
worc1:ir it woLih) Qppcar to be aa iinmiinity which 
16 lb«d LD thd o»)l]«> a etatio immtiDit^-, eo to eay. 
if the eipresiinii insy be coined. II may i3?pend on 
habituation alont-, on an incrcAMt^d power of dc- 
itroying tlin poison by the edlc, or oti a decrvsReJ 
sfllnily t]( tlie cells fortlie |)oi»oD. 

A similar proceu may cxi«t in ftcquired reaiH- 
nnce to somo of 1h« moi^e o.hrontc inf^^ctioTv^ a* 
luherculgsib, kproey aiid oilmn, altliou^h vornr JJI- 
Uo ii I^Dcn^n definiiely Mneeramg it, 

Immtmily vblch re^iUta from an infection de* 
jH^ndi^ nn ii specific reduction on Qie part of tiie 
tiaanc coll* in rosponeo to the chemicnl injnry pry- 
dnc«d by lie bacteria or tlieir toxins. The indicn* 
tiona of the occurrcnL-e of anch a reaction Hd, first* 
in ihii rctov^ry of tlip patient, and, second, in the 
new antitoxic or antibacterial poner vhirh may be 
demonat rated in the nenini or tha incicascd pha^ 
eytle power of hi* iuntoojlee. In r\ew of the BctlTe 
part pl^^ by the body in eetflblishing tliis new 
raaistaflCQ^ tho condition i& referred to as an active 
immunity- In tic preparHtlon of various Anti- 
toxic and antibacterial scrums fur therapeutic par- 
poaeft, a conditjon of active iminimity is deliberate- 
ly produced in the nnimah (the horac, for eiam- 
pM by the injof'tion of the toxin^ or of the boc- 

Contrahviae, ihc r«i*taoce which is esUbliBbcf) 
in an fndfvidital throu|f>i the injection of on ira- 



.^ . ^ {*uct a» diphHieria atiUlr;iiii) m d 

pdnmlminuiuty. eincc it dcpcndv on tho iatT«> 
Auction of TPadf-iDfi<l& imm;ini:ting «i]b«tA£ic«a 
rather thAQ on their prodadicn ihrougfi an active 
prooeaa cm the part of tho one iojootdd. Active 
ami jiaHsJve imrTmuii_VT Uien, are vnrtelies (if ac- 
qtiircti immunity. L)c]>(nidin^ od the d if case 
which C9"6ed tho immunily. cr on the oharact^ 
of ttie Benim iinjtcIoiJr tiiin' tuny be ^n U bar tc rial 
Of antitoxic, or, to certain extent, op^anic {itha- 

Any one ot Uie lypea nieuUonei] may l>« either 
rtlatiTc (parliel) or nbiolut": (corHj>Jcte), II' (Itf 
inimtinity i( absolute, hjffflion is impcK^ibl*', If 
rmly relative* dilTcicnt con<t]tJ0D3 may be mode 
to pt^T^il which would render infection possible; 
foe cunijilti, a lurge RtiniW o! Iru^lerm will often 
CflUM on infection where :i smaJJcr numbt^r fdiU 
to do to^ Thiiro nAv also 1>? a tcmporAry decrease 
in one'« reatsUince through ovemoric, hiJDE:or or ei- 
pomrc. Immunity in ueua^ly r&lativc. 

By proper *v^nibinatinn& of the l^rms whirh 
Imve been enuinoratod. cnt may tiojcribu Jbrn^wliat 
Monmtdy the different form* of immunity. Thna^ 
s child which hms received a prophjlnctic injec- 
tion of dipbthcria antitoxin is in a AtAte of ac- 
quired paulve antitoxic immunity lo diphtheria. 
If immunity to typhoid had developed .-t-t a rct^M 
of the diRcuce, the coniiition is thfit of an acquired 
nctire antihaderia! irnmunity, etr. Accordingly, 
although the tcmw may be «omewhat oonfnain^t 
it i$ wwn that tbey nro in no isenat? irjootradif^tory. 

The foHotdngclawifirnt^on of tli^ ngvnriw* which 
may contrihnie to Immunity in one diae&ae or 
anotlicr may b« giien, althoufih vt mnit recoffalsc 




jyyscfiw j.\D jAtuuKiTr, 

timt it firohttlily Haai uul iiicltittc all Doncoiriblt 


villi ftp*Ob\rui I vrt'pArQtt far ptiAtc^rtdult]. 
Jl. Anilmvlr proiifiUrm ti( thr ftntu nr plBiiinii, rT^uHliit 
ku a iJuitil*- liludlu); ur uciif mlltiiifoii uf I'Jilus. 
HrrKi[ liprli'iillj, ten, ii-rit\n Tprmi'nEi tt Ilia tirHty 

<^ Totul IrijiuKpftprlblllrjr of tho biHlf fo DEutaifiilai cp Bcto- 
lAilniTr 'I'h^rp l« rmAnn 1i-i hl■T1r*^ nlu fhur ruin- 

IlAlftti*!^ lUakUUfr tUU1«l]UJL-« nL^[|4-||||l uu L|]« tqi;;t 

ihut K (oittp tan* n ■(ranprr qltlblfj Tnt orftiou at limt 
Tlla] imiiorlancr lor lAc Ilfi> i\r \tv tudlvlduil rhin U 
Ud' fcr inufo ImpuiiAtir ui-kaua, Th* clilrk'u, for 
ptampio, ii vtfTy ^pilitunf in Tolanug, flEhmLfjh |ti 
tiTtiEn cuulaliiK III) BrlUttrilu. U y1rlil<i. Tiuwriir, 
vhM) liioriilpflviii irc caaili? dlrtioClj tnlo fhn BrLTOEii 
0, Tlirt "uLrnud^' ImJiniiilly uf Klirllcli. lu wlUirb mlcrii- 

Altl« form. In rh* rwir n' tb* lioni- TQii la iltnirftl' 
U IrkrtvQirfl BiillhiK-EfrLftI propprtiM of tbp ncrqae or 

n. IfLirfBiHit <L»tltnKk |<rT>jf fll't at Mit Mrcnio or vlnHmm. 

T'ndcr 3 and 4. fc may hov* nlso to consider sn 

incten&cd power of splitting o? digpttinp toxii: 9u)j- 
9lriri('eL-<. Of Llili^ hcwok'i^r, wa. kuuw uutliiug defi- 

One an(l ^ (powibly aha 2] mar be paaeive as 
well «8 active. These aubjecLs receive further coii- 
ftidcintion in i:iibccr|ii«nt chaptori. 


Th* H^itt. 

Nfttimil uumuuity lo inCectio:! dnpcndK^ firpt, on 
ccrtiim obHtsclcs Ic invMion which ait afTonW 
br the body ftirfacce and liia germicidal etfect of 
their B^retions; and, eecond. on nntibftctoriftl mid 
D&tJtoxic foroM which arc firtxtni in the cells ocd 
flnidf of the int«nor body. 

(J) ProUclion Affardnd hj/ (ht liodi/ Surfaces 

Virulent orKUniunn (c. jc-» slnphjlooooci nod 
iitn^phir-t)(<oi ) nipt imrmilty on thf Mn or \n> 
IwocQ the eupcrfickl homy ccIU. some ciccptioQ/iI 
circuniBtaDcc being recwsary, o, g., woundi, to on- 
abltt therm tr; peiietniU< dwpor nml to cuii^e lii^MuiM. 
It 10 cvi(}cnt. thon, that the physiologic shoddin; 
of tlip fiMppi-flcisl homy cells antl their oontinuRl 
Tcforrnation nt n deeper level in a procP** calcii* 
loled lo nd tho fiiirfaeo of Uie body of many micro- 

Th* qupttirn wh^flipr mirm-orgnnidmn rnn nvnr 
penMrAtc the imhroken aUiti has been much diB- 
cuswd. Althougli expcrimeuU have ithovm that 
travmsUnn U not nbiir>liitcly noccNsary, cliiiital 
«qNri(nc4 indi^^atoA that th«o M^caltod crypto- 
gtmvilc inTccliorj^ ar? not of ready occnrrenL^. 
When they dr> fx^trur. the infection Btrium i> prob- 
ably one of tho glandular orificot, 

lt)o ewoat Inlands with th^r duet*, and Wit hair JJttB-fc 
frOlides with iht'tr appended Mhoceons gloadfl, 


lyFBClifjy XHD tUMUyiTY. 

Ar« vulnerflblo point* m the dafenee whicli ihc 
cntaiicoun surfjicc reprv&cnte. Although tbey arc 
protected toniQwhftt by tha flow of their eicretionfi, 
eipeoinlly in wnrm wenther, atirl Blthougli the eii- 
tiwice of germs ia made more difficult by tho con- 
irftclioQ of the tlcm Mii consequent narrowing r>f 
the oriric^Tfi in rold wentlier, yet vurioiis inctdeaU 
may load to tho introduction and retention of 
virulent micrr-orgsnisms in these filrucfurcj^, 
Wlieu tliifl occurs there la b'ttle difficulty in the 
wAy ^f tlieir pmitueEng neerosia of the epitheiium* 
invaJing the EUTinumliag tiastic ancl causing a 
pustuTo, boil, :jiirb«iiolCt <^elluliti£, or even a (^n- 
evHlizal infection. Tlie sfcnction of th? "^ebaceoiiB 
glands appeate to be not grermici^kl, On the crthor 
hand, tlie acid nature ami certain saks found in 
perepiration r«:ndcr thta fluid ^DtaironieUc to the 
da^olopmont and vintlfTico of certain micro-or^an- 

Tho Aeroua csiudAte, nnd the cruat whii:h fortTis 
■nbaoqucnt to an abnuion, antagonise infection. 
The semni itself contain* g^rmicitlBl STths1ftncTO» 
\vhile the cruat mecliamcally prcveuls rnicrohic 
mvflsi on- 
Soluble poisoQS such HS eoonile ami bacterial 
toxins are not aheorbe^ through the uabrohen skin. 
Even after germs peni-'trftte the epidarmie. thfi 
subciitaoeou* connective tissje is often fln obstacle 
to their further eitenfiicu. The subcTitanoous iD- 
jection of some micro-orgjiniema (e. g., eholera) 
i» loleratod better by Finimals than one pren into 
th^ nhdominal entity or btood ve^e!*, We are 
abo familiar with the benign cnur^ of lupua 
Gcmpared with vise^ral mberculosie ; tho fiamc is 
true of cutantfliu* and risceral glanders. This re- 

MVCOL'S VKitUitS\l!:S. 


n«UDc« is GxpIainablOi at l«a«t in port, by tho 
r«piiditj with vhich now conneotlTe tJBsae iormi 
in the subcuUDoous ti^uo, ofTeritig A tncchiuiiciil 
limitation to the mfrction, uiil by the rich lymph 
rap|)!y which mok» posaible t)i« rapid ftcciimula- 
Lkm of bac-lerkiilttl hriiiTh ntnl of plia,gocjLic cells 
On the other hAcd, it mn«t bo mcntioTicii that in 
fome dJvoatM the aubcat4Ui«oue liesue ofTers no 
perceptible rotUtancc to bacteria] Invasion 
(pUgne), and that toxins may be more virulent 
whaa introdiic«d into thie tinud than wh«n io- 
jftrteJ iulo tht" ahilotniiul uttrity ar iJie gentfritl 
circnialion (tctontu). 

Tho mo)*t condition of mucoiu meicbranQa bas nao««i» 
been fonna (o faTor the mulUpIScation of many "•"'"""""■ 
aUcTobc0t although mucua itscH ia sai>l Id hltttu- 
tulQ the viraloncQ of sonnc micro-orgnnisins, &a 
the pneumocDccn* ; mvciu^ however, is not actively 
germlciUal. A lajcr of munis, on the other hmid, 
U a mechoiuc&] protection, nnd iffi constaDt c:£crc- 
tloii h a meiuw of «ti3a<lily rooionng bacteria from 
mtiooufl eurfat^. 

The coLJuuctiva in protected a^i^^t infwlio^i coi*jih»«ih». 
by the mechimical interference of the o^-cbrowa, 
«>^A«he^ eyell^ im'^tjon of the conjiuictivflj 
ffurfdce by tewa whidj carry gcrnu through the 
laehrymai doct into th^ na»ol cavity, the ability 
of the conjunctival epithelium to repair itficlf 
ra|ud]y, and tho mild geraiiddal Action of the 
•aJta which aic preeent in the teara. I'hcK pro* 
tecttve flg«acu«, hoi^-ever* aro ofton gurmoTinl^ 
hy mitnMir^nniarTiH, civ-b n^ the ptiruTiiormvus, 
•laphylococcua and the iDilu^nsa b&cii3us. Many 
•o-lnble poiEona, aconite, diphtheria toxin and Uu 


tsr£V7Jos j.vD iMJtvKrrw 

toxLH of hgjr fever ara readily fiUorbod frotn the 
VftHii OATftr* Compared nith the autonoi* Qarm, tJu posterior 
aw poor in micro-or^iiuiliinw. ThU. in port, at 
least, is di;c to itm tortuoailj- of Uic clinnncls. rA;is- 
tug duEt aiiil bflol^ria tc strike tlio wslh where 
ther are li^lil ly a nioiat eurfaoe^ and the action 
of the ciliated i^rilhchum ii^ carryicj; them iinb«d- 
dad in mucufi* again towaH the anterior nares. 
Xcveitlielea^p LUe nsfia] mucoii! iitciiibranc ui a 
comuion tnfovlion utnum for fctrepfococci. aloph- 
jlociirti, diplitiir^nu nnd innti^nui imcSllI, ili* dip* 
lococcua of epidemic mcnin^itie. and, probably, for 
other infoctbufl a^'t-ou. 

Ala«fb> Wry many »:pctt'iri of miVrn-firgnTnHm»i Jlour- 
i&h m tbo oral cavity, some of them being path^- 
(?eni(*; ataphyloooooi. streptococci, pceunmcopri, 
Rj\\] oUi^n *3ipbtlitfri« hwilU. They are cousUutly 
romovod with tho laliva, iind through the exteii- 
eive ^ewjiininiitinTi of thfl epidrrrmia dcPttsiotietl by 
mwticatioDH Saliva is not pirmicidal. but in- 
liibfts the growth and ueakeiu the virulence of 
taints UifUxna. Tlic fetid brpntli and Ibc aor- 
diditi' ohuervcd in forcra whcro tht* mouth if dry 
are attributable at Ipaat in p^rt to the lack of 
aativa with its Anti -infections propertie». Tht 
great rnptdity with whic): voimd* of tho mouth 
beal ia a potent factor in prrvrnting eenoua tnfm- 

LiiD«4. Micro-organisms do not ren^liW roach tho ulti- 
mate ramifii:ationB of tbe bronthiolef, Tn cinlimiry 
retpiration the velocity of the inepircd air i« «o 
reducod us it ne*rs the alveoli thnt the fnrthor 
n:ovciccnt nf the ^afiee ia one of gratjHal dilTusi'iii 
more than of violent adrntnure, Con*equeatJy 



there are grwtcr opporlunitif^ for s^Ttn^ in come 
in contact with tho broochioJ wails wlicro tiioy 
become imb^diilec] in mucua with wliich they may 
be expeUcd hy cougliing aiid the actidc of ihs 
cilifitoil cpitbolium. Both Ihe n1vvv>Inr cpit^K^Iicl 
cells and tlie letirocjlea vhidi oDter tJie air sua 
and bronchiole^ bavc been thown !■> Ickc up hoc- 
thrift. Thf> ooTi'lEHons in the lun^t vvliLcb favor 
Ihf; development of infections, a4 bronchitis, pneu- 
monia, inltu^za, tuberfuloHfl, are by do meaoa 
dearly uiuli-iwlootl. VnriatidnK in imJiviilual 
r«a»tancc, bcrc^ as in otlicr parta of the body, anch 
ii naj bo cauflcd by upoeure to cold, ai'c certainly 
of great importance. It is probaiilo tbnt tbi^ tung 
la the infection atrium for & number ->f our acuto 
infactiove diatta»«. It haa been demoni^l rated tbat 
swtriDu-* tnf(«;tionH, aa ^ith anthrax bncilli, may 
be caaacd by the inlialntiou of the uiici-o-organi«mEi 
The gnatrfc juice, through tho hydrochloric 
add it r^<)Qtjitii\ in iihle to liill anlhrnx, typhoid, 
tubercle bacilli, cholcm ribrio and other orfroJi' 
iamA, Clinical and oxperimantal evidence *how« 
Ihnt thin powi^r i» oftrn ii^ndoquatc^ virulent 
micro-oTKanUmu reaching: the itit^ttinca in «pil€ 
of it (typhoid, cholf^ra^ dysentery, lijberculo*i«» 
etc.). It ia probable that bA::lena in the stomach 
are oflon protoctotl ngninH tha oction of the if"^- 
tric juice io norne extent hj being imbedded in 
wlid particle* of food. Certain acidophilic gorma, 
11 well aa yaaata and ronil«% wMfm t« floiiriNh in Ibe 
gatfrle aacretiov, these fire far^ly non-patbo- 
f^enic, but the re^^Iarily with which peritonitis 
follnwN []i!rfnnttiuff woimdM uf Uie MlDiaaf^li ludi- 
Mtas that it probabJjr always contains piilhoffcnic 
bacteria, tboitgb it may bo only their f<?mpnrnry 



J:^Fl%'TW^ -ixii i^t^tvsiry. 

habitut. The gwtric juici* mar render some boo 
t^rla harmleas by di^^Liug tbdr toxins; one 
(jrflm of tho gastric juice of a dog will neoiralii'! 
fifty ffltfll lioswi nf (liphLUt-ria tniin, or 10,00ft r>f 
tctJinuA toxin, ttaing the ^Ltioea-pig as the test 
Animal. On the other hand, the toxin of the baoiU 
lun of botulism (causing a form of meat poiaou* 
iDg) sccmB to be imipflncnccd by the stfjmach cots* 
(cntd, as the davolopmeiit of the iDtoxication indi- 
cftttu. Vontiting is ofien n nicaas of riilding the 
vtom&ch of toxic aubetanccd, icclnding bacteria. 
Th* stomach its&lf is exceptionally free from io- 
lav**!!***. The hilo is moderately bactericidal for sorue 
genua, but, on the whole^ the intestinal Becrctiona 
have lew germioidol powers; tlii* Is indicated by 
the fact that tit^ colon cootnina roany more bac- 
teria than ihe diiodcn^im, On the othor hand, 
the j^ncrcatic juice deatroya som» loiiuFi (dlph- 
theriu, tetanufl) niore I^o^^'e^fuUy evca than tho 
gaatiic jrtio^ Thf< ability of tlie pimrrentie juiije 
fo destroy toxic bacterial products may cKplaia tH« 
more fn^quem occurrence of cnteritiB in the ikum 
than in t}to duodenum. The bile aleo has a neii- 
trali^jng power for some tosiiu. AUiiougb a num- 
ber of paitog«itic bacteria inhabit tlLe intestinal 
tract (colon bacillus, streptococci^ etc.), they do 
not often vet up inflammatory prcccBeos in the 
adult, Thr tissuf^ become acciietomed to Uieir 
proeeBoo. Ilio pnthogcnic bacteria vhieh do net 
Bonriiilly piT=t in tlie intestine* are those whi[;b, 
on iatrofhictioo, arc roost^ likely to caase diaeAae 
{typhoid, cholera. d>'fi©ntery, ote.). The intosti- 
nal tract of the iufant, on the otTier hand, ia fro- 
gently nttaeVed by aomo mCcro-organiems (atrep- 



colon liutiildj- JiaclUta jstfvctiaitair*), 
in the Mjne localiLy in Ihc adult nppGir 
hmnnlcwL Tho fac't Uint mnn^ intltriJuiibt ura not 
stricken in an epidemic* in which all are equally 
«ipo6«J to iaTociion, pointa to the probabil% tbat 
pathogenic argaoiamfi (typhoiJ, t^iiolera and Jve- 
esdtry) ofttn trarer>c the iTi(<K^t[iiiil cunol without 
fndudiig dis^uc- Natiinilfyj miopoltes are dimi- 
natcd in cnonnou* qunntitics io the feoesn oin3 in 
mflammAtorr ^tat^ thia «limiaation is Incroaaed 
by diarrboa. It 19 alfio not to be forgotten thflt Uie 
inttttinol tract le^ to a coneidorabic csttcnt. a 
lyropliold or^niK nuJ thiit in thi^ presence of infec- 
tion cnoTmoim qiJiintitics of pliagocytea c*o be 
cftlW into action qnickhv 

The protective j>r[)[>ertieft of the grpnilo-urinary 
rarfocoi are not dilTcrcnt in priiiciplc from those 
almuly mrritinntil (vnifinnl nri<1ity, merharitcaT 
•ad perhap« ba^t^rici^lal (leanajog by the inen- 
itrval fiow, urioary inj^jatiou), 

(£) ItUemal Protective A^ndea. 
A. Injtammaiian, 

Allltough there aro many chemical aaci physical 
ftg^nfa wbkh muy caiuto ][i!lHmmution, we are in- 
t«rc«torl here only in those of an infections nn- 

TnflamnnadoD may be conaidered as a rcactivd nAtm 
condition on tlie part of tlie tinauea, which 4!erel* "■'"*! 
opa in rceponftft to the fictinn of name injiiriou* 
■g;pnt. The pnv«^ft* tnny bi> bftin>flcial in ftomp in- 
stances, while in othcra it xaay he pernicious from 
tho bo^nnin^ I0 tho endn Tha thickening of the 
eadotheliiiii) of the cerehnl vmselit hk one kcm it 
in •jphilin i^ ■ proirn»<iTe. rcactire chance which 



tyrtscrtoN AXD WMUyiTf. 


ID no ecneo con bo of benefit to the mdiTuiual, and 
wliic^h cfln ha« no ootio^iv&bW function in over- 
comm;^ tie syphilitic mkttiori. Liki;wi-e, tbe uew- 
fonned conoiK^tivo tisetie ecen in nlcolvoJic oirrho- 
fiis of the liver is of nn bcnt'flt (o the hppnlic liK^iu", 
thou;;b it mev ecrvc in soinc dc^roc to protoot the 
Jiver cells from the alcohol which continues to b« 
iD^etetl, Tn an ulcer of tJip coraea the preeeuce 
o( serum aD<I of loucooyt?^, ne we!! as the prolifor- 
nlitiri (it p(»MmH'lii-" fining may he Hic sitwt fjjm mm 
for the hojilinp of the (ilccr, .>ct the rc.^ultinjj acar 
mnv grently impair the vEeion. The inilsimmation 
in the iiialnncCA cited h iajmous Lecauae of the 
fimctionfll impnrtmice of tho tiasues involved. On 
Ihr nlht-r bnn<V iin Mftusive s<?ur which han 
filmed in tissues of I*s8 fonptlonnl importnufic, 
as in thf^ skin fln^ eubcutaneone ii^nt*, may be 

It ji, then, to Iw rwo^iiod that Ihore am cerUin 
conr^^uencert af the inHfUnmatory reaction, Ihft 
eenouftnesa <)r %vhich depends on ihe eituation. 
i^i-erity, dnrfltion nnd oxtent of tho proeo.ti:. and 
thflt theire L'[>niei:nieTi'va iire imiependcnt of nny 
protective function the iuflamrnation may hflve 

Thp umuuiil ivnd clmiticfw (if Un- rertctitm ai* 
Buhjccf to many Tariatiomt, depending on a num* 
ber of conilitionii : 

1. It variea with the nature of tha microbe 
Non-pntliogcmc orpanieina induce little more in- 
Summation Ihnn *o many mtauEe, inanimate, 
Don'toxJc partictcA. The tui)ercU bacilluH causes 
«e.pecUlIy the formafSon of connodive tisauo, 
giant oelU and the accucnulation of lymphoid 
wlla, aaido from tomo retrogre^ro changes char^ 



ftft^iitic of the c1iBRiiA(>-. Or^Hnisiiifi simikr to 
tlie streptococcus And pneinniococcUA lead to the 
formulion ot p^tf and Itbnn* lo th« ACCumuUtion 
of P4*rmTi nnd of iiolyruorphoiiucluvr letacocytos 
more tbon TnononiicTo«T«, whorcoii tlic ]>rolifera- 
lion of flsftd tl«fli)« elpmpnts is sornndnry. The 
tctnu bacillus alone causes alrtioat no local in- 

2* The traction is inflTiriirivi bv tlie lirnlunce 
of A particular fclraiu- A tlreplococciip v^hidi 
Im ]<ai ibi rJruleacc is tSispoa^ of by the anhnfll 
liasntt with n mbiintint tiwLe reaction, perhaps 
00 more than sU^ht oon^cstJon and edema and 
the wandering in of a few leiicocjtert; ont^ of higli- 
«r Tirul«nc« causes on intonae reaiction, tiaoni- 
fcKtod by conge»tJ(H), edema, hemorrhapea, necro- 
BJs and piifi formntbn; then atreptococcl of such 
(^rcat virulmwo that they ti«€tr>v lif« *a Iho cmira9 
of w few hours wre ocr^asronallv enconnterpd in 
vouid infectioa^ and itj ficntonitia, having in the 
niMntiino clieitol a mUiiTnum mflanimatory rcao- 

3. It has a relation to tlic rojiiatiuicc or the not' 
tiriil immunity of t,he tndividnnl. Moichnikoff. 
in partjcular* htm. tihoint that uaimuli of hif^h rc.^- 
aifftonce to 6 porticulor mi^^roba dt?fltroy tha (fcrni 
i|tilckly by phagoo)'lDflU, v)ii!c in iosooptitlL* nnU 
[uilfl tJie nccumulatioji nod aelivit\ t>f ^riia^jo^Alic 
konwYtea are deJident. 

The oocurrenc^d of louoocjlca in inllamrintory 
CDnditio7i4 \rt nn chtimcimsiic tluit one tmlurnlly 
aeoka to aMOcintc thdr prcacnco with somc^ in- 
f oenee vhlch is exerted by the toxic BuLetance or 
the hocteria which canae the inflammation. It la 
fl long-Jniovn fact tlint eomo microbw nttmct one 


146 tyF£CTrO^ AXD WWMTY. 

kiod of ImiDocjrier that otli^rs attnict anot}i«T 
lonili fln*3 that in «tiJI other instances tlie Icuco< 
c}i«s appOAr to b« either uninfluesic^d or ftctuallj 
jin.' lepelicJ bv iLe iixfcctiag agent. 
Ck«B4aii>Bifi> The iihcnomcnan of livinj^ celb moving tonikrcl 
or a\\»y finiTi c<>rlnin olhFtr ppHs or suhsinnrfs ik 
an eipreaeioii of uttluitj and tiiis afhiutj is known 
w diomoUxit ; tht? fotmoT is positive, the lat- 
ter np^ativc, cbcnmtnaijs. There is & sotnewhat 
gcrccral Iott, but one to which cxccpUonn cJtist, 
tlwit, wgartlloas of the microbe involvetl, tlw mon- 
ncutc? tlic rnllmuni&ton' proceM the more do poij* 
morp1ioiiudi.*iir kucocjrtot nccumQUte, vrWe io 
t2i« irioio clicviDi? infccHon*, witli much cxinnec- 
tire tis?uo formation, the mononuclear IcuoocytM 
pn^dominale. Thtis in tuberculosis on? finds 
[>tnphocytce nnd pluma ccIJa — niononncloara — 
prcdominAtin^ pwtly over the polymorphonii- 
He^rs- fn t>i(f iLcuti^ purulent infit^tons, on IJii' 
other hui^^ti^pioooccus, etaphylococcus. pneii* 
moooecue — the latter type of JoGcco>'tfl predomi- 
j^atiw:. thp mrtnrtnorlcjiT* In-mg fewur iu»l rwmiio" 
tag at a dibtflnce fnnn the center of action- There 
tfi reason to bolioro that the tnononnclear l«Qeo- 
eytot play an important, tbon^h perhaps inflin?ctr 
rdte in tiie formatioEi of th^ i^oDnrclire tissue- 
ri»«L«««i't**u. The ingoetion of particlca by living c^lts. pha^ 
cytoeia. i« a properly vhldi many c«U« poneas. 
Although micro-or^flideina am! imuiiiuate parti* 
elea ara aonMtiBMi found in epithelial e«!U, c«r- 
bun of the loeaoblaa^ edia hare thit fnnjetion 
pre^eTDLMDily: pofyniorphoAiuiear leaeoc^ te«, lar^ 
infUKiDi»clcv Itfoo^'ttt (lysipfio^p^K ntnehoid 
convcctire tUane and enlothelia] celU. Of Ihne 
the poh-morphoniiclwr leucocyte*, the micr^phagH 



of UctelunlofT. htt^t the grealeal jjlias^rylk jrow-r^r; 
the othcRi, Uku macrophaifM, Arc more exception- 
tUf phagocytic, but eomff of tliprn tnke tip «iicli 
c<ilft u eiTihrocytes and other tiMUO cclld roadilj. 
^ow, the inero iofsoetioti of the bacteria ly fucii 
edU iroTiM not \tw iif nifiTK^ity injiirmiiK to th« 
miofobCid; indcctj, oppon^^ntd of MctchniArotT's phu- 
lft>cyti« tJj«n' of imnivirity h^IJ that phagocTtoaia 
hf wnnilenng cvlU nm br, ntii] often iv, purnitioua. 
in tbfit tJio ccIU iR&y return to the oirculntion und 
ipr«a4 the Infection to other parts. Thin ia pixih- 
ablr true in many malaccfla. But when wc 
I earn UiAt after in|;cctm;; tho bai^t^ria tho phago- 
crtM arc often able In Vill incT tWgy^i thnii, it ia 
rcalbed that tlic proccaa ruiiy be a gcnnina pro- 
tectJTo factor. Thla bdng true, the importance of 
pcntiTe chcmotaxie in rccoTcry frorn an infcctioa 
becomea manifeat It U aUo repr^Mntof! that 
pha^ytic wll* lifti'i* the |xiw«r of f^iL-rdin;! Ih^ir 
germiddal eub^Uncea into the plaema ani sprura 
and lendinfT to the latter n bactericidal power. 
Furthermore, it h held that they inay abiorh Ifqtiiil 
poiatma* bact^tal toxins, £m] in vjuie mmuuT i]i?- 
etfoy their toildty. A* Hhovm Jotcr, th-^ae are e«* 
aentia) potnU in tho phagocytic theory of immun* 

Serum, ercn whrn entirely free of Icucorytf-^. 
luw boctericrdnl power* for many micro-orgsni&rns; 
it need not he diacuased at present vhetTier tbk 
power eiiattf pniranJy in the t^nim or id one con* 
ferrnl on U bv the leacoL^ytej. In \hw of it« prea- 
«iice> hoirever, it h evident that the serou* exw 
date whieh ia tuually present m inflammation*, 
etpedaUy the acute, may be of irifltic<tici: in c^nn- 
batin^ the infection. Seram mav contain natural 



txFEcrwy AXD wAiGstfy, 

antitoxilis, and, in addltioD, it may be of vuli^c 
10 Icttwain^ tli*; inAictO' of poiMcns by diluting 
thctn, aiding iv ihcir elJininatioQ, or doetroyititt: 
them by means of fennenli ( 1). 

riLriu. Xlie Abuodfint depoait of ninu taxn in «oinc in- 
naaiication« \a of mechoxucat valuo by hcmmiDg 
[u tlie Jrifi'tti'Jii «m! by offL'fing: u TmrritT tn Ihf 
rapid UiffiiAJon of toxin«. Wg arc nil fnmiliar 
with th« part pUyed by ftbritioua ard flt>roiiG Bd< 
Ite^ioDs in prwieoLiu^ Ji localized jwrilonitls from 
becoming genera lue^I. In prolonged inllammfl- 
iiftus fibrin ftimislies % grmmfl snlvstaccL* into 
vlucb nev connective tissiio aod vcjwJb grow (w 
isMftmibAiorr The rew-formcd ^nu^tt^,^v^? Ils>i)p *.et»n in man*' 

Tiunv. innHminaiJonft, efipeaally tht chrome, ai m tuber- 
<ulo»i* nnd notinoiiiycoftis, otr*r» an impoitHDt 
bftTricr to the evtenjion of an infcctioii. Porhaps 
no hotter ejaaiple of ihia could be cited than the 
denBC tiMUo vrhicli forma nronniB a tuberculoiw 
Pinu* OP abwe». 

To «uni npr the InilammatDry rcection nntngo* 
tihv.% inf«-tions» {I) ineclianirjillv, thnnigh tlie 
rormation of nev conneotive tiaeue around tiic 
focus, and denae acxrtimulatioju of leatwcytei and 
fibrin: fE) through the bactericidal and Hntito:iic 
uctioufi of the hmpb and serum; (3) tbroui^h the 
phagocytic actioi] of ameboid 4«1l«, 

The vahvi of hot appUcntionn. titkH B)ar« pa««ivc 
congestion Irealmtnt, in loml inflammationa, flnd4 
A tc^ical cjiplanation in view of Lhe facia mmj- 
tioned, in fhat lh<^y inorefl?« con^itiom, which 
haatens tbe Fnidation of pluMun itnd hmrwj-tes 
and tbc pioliferatiotn of c«)U. and accelerate the 
olbninitfAn of toxic atrbalanee*. 


The Epeciml festures of the phagocytic theorv' of 
immuiiitj «re considered in a laier chapter. For 
tnanj deuils id regard to inflammatioD. the reader 
18 referred lo the clonic article of Adami on thU 
fobjeci in the first Tolame of Allbntt'g ''Svstem of 

B. Properties of the Serum and Plasma. 

We hare seen that the protection afforded br 
the body surfaces may be effective against hotli 
microbefl and their toxins, and that local inflam- 
matorj processes^ although most certainly antago- 
nizing ihe bacteria, may at the Eame time have 
some antitoiic ralne. 

The terra "natnral immunit}'/' however, as indi- Jfam^n 
cated in the preceding chapter, has a peculiar appli- 
cation to the natural resistance of £ome speciea or 
races of animals to infections to which other spe- 
cies or races are susceptible; and to an unusual in- 
dividual resistance often seen in members of a 
given race or apecies. This condition depenrk on 
properties residing in the tissues or fluids of the 
body, and consequently is independent of any pro- 
tection which the body surfaces afford. Its pres- 
ence is demonstrated in the most striking man- 
ner by tlie esperimental method^ when micro-or- 
gani&ms or toxins are injected directly into the tis- 
sues or cireulation. At the same time everv-day 
observation provides many examples. 

In certain instances natural immunity or sus- Kftoi»t«Hi 
ceptibility shows a relation lo zoological affrnities. ■hip*,""" 
Thus only man and the higher apes are susceptible 
to syphilis; and only animals which are closely 
related to cattle, as sheep, goais and other rumi- 
nants, suffer from rinderpest. There ivre many 


isfficjios .i.\o ;j/j/r-virr. 

Fiholorfe lift 


exceptions lo thij^ tendcnc>\ hoiwcvcr; pcrUflpji Ihe 
meet ttrikiDg «iftmpl9 i^ found in the fact that 
rtlioriraa ^lieep onlin-irily nit- eitn'mrly suflwrptiblf 
to onthj'AXt Algerian sEi^ep aro r<'1auv-cly immune. 
Similarly the while rat lE imirune (r^lstiff^Iy) 
and iht vilJ vHt is Busceptible to nnthrctx. 

Natural iiamuiiity may de|Mii<j on a Inck of 
pHthog^nicity on the part of the cr^sninn for the 
htmt, which it eqiiiifiTent In iniiii_=<*eptihility on the 
part of the host; or^ on the prc!M!nc«i in the host 
of a euflloJont quantity of Qniibflclcria] and anti- 
toxic eubsliinoes; or, as aiiggested by Ehilit?h, on 
the indhility of tlie micro'orgiiniam to proliferate 
in tlie host because proper nutritive subrtancea are 
not prment* or^ if prtsert, are boimt! to odior sub- 
«tH.nrMK ill Aiidi n way that t>?ey are rii»t avuiljilile ta 
fuoil fur the organisms, 

Ai aUted in Uic prei^edin^ diaptcr^ immunity 
nifty be either anlibacrerial or antitoxiCf h e., the 
immunity may in utir la&v dep^nil on the powpr 
of tlie Animnla tificiuef^ And fluids to dcatroy tiie 
micro-orpiuiBmfl, or, in anoUjcr, on Ihcir power 
to nentrnliw or destroy zh& bacterial toxins. 

The dislinetion betAveen antibart«rial and anti- 
toxic immtinity i» demonstrated more readily in 
acquiriifd tiiau in natural Immunity. When one 
haH recovered from t.ypboid f*v*r, for example, Iiis 
lerum baj4 at^uii'cd nn inrrcnfrd pnucr of killing 
tlie typhoid becillufi^ whik at the same time it 
appears to bave little or no power of neutralizing 
Un- puiHuiis of Ibis organism, .\cquiriil immunity 
t« diphtberU, on the otl^r band, ie cliaracteriBod 
by tha pcw^r of the terum to n«utrali»f the toxin 
of lilt diphtheria bacillus iilibougb it hardly 

r¥psa OF mumnTY- 


uonual Mrom in iU bjict«Tidr1a) ^owcr for 
f!ii? Wllltis iUfllf. 

ilATins pKcrUined by obxcrvKtion or oxpcri- 
nmit thJit ft ccrtdiQ ep^cie'^ 1ifl£ a degree of immun- 
ity to an iulwibti. trerUiu line* of JjuvttftUguUciu 
mny be foJlirtwcil for U'rc purpoite of determining 
tlw chftract«r of the immunity. If thp animul 
fails to become infected Wlowing Uie injection 
of a living and rinilout culturv, it h fail- to u^uin« 
t)iitt Ibt^ <>r^ciiKni« hnvu Iilvq killcil wiOiin tlit 
bodir of tie animal. Tliat tiiia hii» bccD the result 
Tnay. inJet'J, bt^ iloterminod l>y mioroacoptc esam- 
iiuittoit of ihc di[Ten;nt tiAf uta liud by tbtr inocula- 
tion of culture media. It is oft^n dopirablo to 
dvterrulne iiw ext^ul to which micro-orgAii{»ms 
arc eliminated ihrougii the excretions (urine nnd 
fucoa) ; thie u best clon« by Llie (:ulture method. 
but it JM uftL-u a diflltrjitt ttchuicJil problem. 

The natural iinLibiLctt.-niil fonxa with which we 
are famitioi- eon»itt of the genniciilal actioti of 
till? «nim and plj^njs^ auj^ ihe phftgot^ytio aod 
daftnictive actioc of the Ic^ucoc^tcs, cndothcliol nritl 
Wfhipa other celtj- It i« diffjeuk to obUm taV 
{■factory raoIU b) a «totly of thes« fon^ witliin 
tlie body of tlie animal, poiticularlr ah rcinird^ the 
bacteHoJdal action of tlie lerum und pliujitn. h^ce 
such stndicf are usually i:arricd on outsitle the 
body. Soch o^erinueata are open to the criticitfmT 
hovei-er, that the artificial condilionft ar# fur 
ranOTCd from ttio^c of the body, and that the 
ntnlta do not altraya ju^ify ita in dravin^r con< 
dttMOQf regarrliu^ tht ixjui^e of t^vi^nla ivithin Uic 
body. Plia;:oeytmiia under natuTiil eonditionft ia 
iDon «u«c^tib1c to Ftitdy, nnd il is to be remem- 
bered tJiat Metchnikoff came to hta far-readiiag 





GOllc]t:flioTia TegArding the imponanoo of pliAgocV' 
loFU puvBlv from a aEulv of tlie proc«AH in rtrt>- En 
tfpite of this wc have co]»« io a better uii<I«r^ laud- 
ing of the mccbamgm of pJiitjcocvtom by studies 
of tho phF^oomf-non und«r artiffcial conditional ai 
will oppffar later. 

lu dt-lcirEnmaig Lhe germicidal action of cienitn. 
v'hit'li thriulil be fiTshlj 6htuiriwl, it mnj be 
mixed Willi a eospcHAJoD vf tlic tiiiciobea Id a 
numbor of t?»Miibc», vorjinfi ainoanle ol mjixat 
being iiEM^d wiUi ifiiiitlatit jimuiinU of thi- brif'teriii 
in the diffcixmt tube*. At n aubsequeci period, 
from Uiree lo iw&nty-four hoors Ister^ cultures on 
Petri platfti Hrn mude from Iheee niixtuiei. Tiie 
uunibcra cf ooloniCE» which nppoar jn the^e {■ulturon, 
CODtpiir^d with tbo nnmb^i' vih'ic'h Hppitjir vihvn 
serum i= not udded, ia an inJcj; of tlie bflctcricidal 
jHfWcr of tlii; icrum. if thi« pouor ift fouud to be 
high, it ]*, in the prpiciit slalt of our knowledge, 
confiideied at j^'f^^'^^ptJ^e evidence tliai Ihe Mt- 
oral immunity of thL' animal depends on it, at 
luft in part, Jt ia, nc\-crthclcHii, a fnct (hat the 
aAtll^Qctorial immunily of an qnimal daeii not 
alwuyfc ^0 li&iid iJi hand uitli iht^ baoivricidal power 
of its ncmm. A well-known illvrtration of thU i* 
fho lolloping: Both the dog antl Ih** rat burn n 
i'u[]iL'i' higli degree uf immuiilly ji>;dtfiM[. infectiutit 
w:th the amhmx banhuft; yet it baa been found 
timl the uprum of thi' dog Uiw almrttt no burtrri- 
cidal effect on tlii? microbe, while that of the rat 
hflB n v?n- strong: elTeotn At llie *ome lime we 
should reniL'mhi^r Ibat thr burtnricidHl [Miwwr of Ihe 
ftcnim dop* not nccpasftrily represent the entire 
antibacterial function of the borly. In the eemm 
we have none of Ihe body cells, and cipt-cinllj none 



of tlie ^httgocyttif the dcfitructiv* action of vhlch 
OD foiiie IjaclcrJa i* v«ll known. Uanj micro- 
»rf»ri^ma. indeed, which aro not destroyed bv 
wrttm Hi ull. an* rearlil^ Iiigealed nitd kilM by 
leucocytes (rtuphj-Iocow^ streptococci), 

As n consequence of fuudaroc&lal studios by J'MXi^'^*'*^^' 
iJpnys and l-« i.lpf, by lipiiiliinHn^ ljy A, T^, Wri^'ht 
«Rd oUien, it 18 now poBsible to Atud> phagocytosis 
in dtrc vith n degree of ■ccuraoy not to be approx- 
imitediti the lirin^bod^v. Ithasliecn leatitt-d tlint 
leucocyloe, ab t rulc^ are not able to take up boc- 
ICTU until the lalWr have been a-^teil on (fipn*U 
tixed) by >omc ^uhft/LOre whirfi U ci^nUiLDoil in thr 
AOTum, Wright pivq Uie nonie tif "opsonins" to 
tJtese Bubstances. Sonie- of them aie giifc^ptible lo 
heat (65 C). while oth^ra are luudi more noAt- 
Afit. 'J'o tliD kttc*r. uliich uro gently mcrooNed by 
infuctLoii or fiitificiai imnju nidation, NoufcM hac 
applied the lerm "baetetiotropiu*/' 

LeUhmai3*i( nietlioci U to mix a *UNp&t»taii of 
the hactcriii with dellhrinatod hlood (uoiiUining 
loucccvtca), incubate tho loivtmi? for ^ft^en or 
more minnte^, to maVe and stain spread prepara- 
lioiu on »hdcA. and then count the numbrr of buc- 
Icria which Imvc been mg^Ated by tho leucocyte*. 
The average rrjfniber Iwken up h} fifty or more leu- 
cocyte constimtee th* ''phagocytic index," Wnifht 
hat ¥Ancd thti l4]chni'c in f^rJfrr to *tudy the epfioC' 
ina quantitatively, on will be cle§cribe^ lattii. 

Expehnicute haTO aliowo that all tiornial seniins 
contain opsonina for a rarii^ty of nfiiciyi-OTgimiNnut, 
and all micTo-organicma are aufccplible to phagocy- 
toaia bj tl>e blood or one or mord animala, in case 
Ih^ir Tinjlmf'^ in not rxn*B<i\p. We have erery 
reason, iherrforc, to bclicro tb£t phagocytovia it 


i^TECTiOy .iXt> i3I3iUKlTl\ 


I m Ik lint I r' 

on iinportunt QiUril protoct^vg facb>r. and in 
*oni« instances it h Lhe only one whidi can \i^ 

af^tualEv dQmoiiatrate'J. at in tbc com of Atapbrto- 
o<>(:in and tliefttooocci. 

Tliat tjrgaiii&ms ai-e often cWtroye'l iifter Htring 
in;;c«ti^cl by the [cucccTtce le manifc^i from changoe 
in form wliich thflj undergo, and from tlie lots of 
their ateijung iio^er. Cuhivatjoii cxpenmcnU 
hiTt alao ahowu thnt the Eeucot^ytcj^ nre nblc to 
T(ii] rprtnin hnt-trn-ia, Tn tnch «xp^rim^te, the 
Icchnic wliicli vaa mentioned tn leating tJio l>ac« 
terioidal power of *urum may bo usad, in thi* ea«, 
iLOwcvi^r^ VLiU^t.ilutiiig di?rihn[mtj>^ i>!oiid, wbich 
contnjne louci^cyt^s. in ploco of tlie eerum, II the 
bfict^ricidflT power of the dci^bTinate^l blood ia 
greater than that of the senim alone, the effect of 
the Iftncocytrtfi Wo me* «p parent. 

At a time when ih$ antitoxic sction of fi«rum« 
WAG not nppredated, Budmer gave tlie name cf 
olcTtins (fiom the Greek, dw;n', to ward off) to 
the prfitectiva snbslanpci of Ihe s!*riim» u e,. to iha 
lacterit-jflal stibfilancee. niaking tlie obaervatioD 
that the>- were very labile subslanccB, losing Iheit 
powor apontsneoiTfllv in a feiir days when expf>Hed 
to tlie air and liglit, oi wlien ihty were heated at 
5C C\ for tliirly niinutean As u'ill be indioated 
later, till? "a]ej;ins'* are more complex Ifinn B^if-lnitr 
KUp posed. 

In dfltermining tb* preeenci? or absence ^f anti- 
lojtie immnnity, the toxin of the microbe, of 
ccurae, mufit first be in hand- The methods of ob- 
tiiining loiins will he referrrrfl ir\ later. Tf tbfl 
animal resieta a doa? of toxin which, in proportion 
to weight, producea diflen=i> in «oTno other suseepti- 
blr nnimnl, tlic tbnuea or fluids of tlic firfi anlinal 

AyTJToxw syvuA'iTV. 


tDty, or m^y not, cenlAin antiCoKlt). If the rui^t- 
anre i» rtfcrnble l» Uie pnj*<-[ic« of antitoxin, the 
UtXw m«v bo d*lect€d in llie foUowiOK mniiacr: 
Tli^ AnJniJil \* b\t^. ild *t*ruin rollwtwi from th* 
dot, Ui«o mixtijicf cf the ecrum and of the toxm 
aro injficted into £n;iDalB of known Auacoptibilily 
Sot ilw U)\[t\. If the tnt tiuiiiml U ill Uiia wuv 
protectctl from an oclicrwit^ f«to) dcvic of tlic toiin, 
It lit «Tid(<nce tbsl the Mrura eoaUios an antitoxic 
eubfifaiic«. Oil Uie other haud, if Hit M?tuni sImjwi 
no luch &ntitoiic effect, wc nntiat condudc Utat the 
iwwtMurR nf thp nnimnl ik i^hp to ollipr caue^; as, 
for e:Lfimplc. noQ-fluBceptibilitif of the tiMuea, 
]»ow«T of llt« llvinfif Milt or femicnlA ta dwtroy the 
tnxiit, nr nbM>rjition r>f tlip toiin by tiuniCH of fii?o 
Mi^ary importance to life. 

Follmring this niothod of oxperimoDtntioQ, if 
aotiWtvrial prapeitii«« are fi^uml lo (be eii^lnsion 
of fttttilOJEic, ihe immLmity is coaiidered to be au- 
tibBCtorial ; and with tUta i^oiivrnMi remit it is antE* 
toxic, or dtpendc&t on non-su^ccpiibilit^. It is. of 
COUTM, conceivabif.^ tbai in a ii^v^jt c^a^i? it raif^ht lie 
both aiilitoxjf^ bml utrUiiNdrrijiL Ux d«'uling wJtk 
ditCflMS of wbidi the vpccJfic microbe is known 
uid ctilHvatcd, the exi«t4ncQ of atitibflctenal or of 
AQliloiic Aubetatit*^ caik tuunllv lie tavml by th* 
incthAdf d««cTtbcd. If the etiology iB nnknovci* or 
th« miero^rgftnittn cannot be caltimtod, as in 
Bcarl^t ff Tcr, ineaftl««p «tc„ 1)mt ii^ if the vlnie and 
its t03un cannot be obtained in qaontities the 
nature of tho resistance is not at present op«n to 

It b sdiloin that nnturftt icaiditncc i^ absolute. 
PaetouT foTind that Uio ^oat ii&manity of the 
diJdDeii for anlhra^c could b? oTercome by iiti* 


i\yi-:L'Tios A.\ii ihiiLMTr. 



mersiDj* the niiinial in eolil whIgt^ th@ r^tictior 
in boily Icmpcnilurc nuppoMdly ciocreOfting Un^ ro- 
ftiitnnc*. It wftK ttufpri prfrvJoiitly (hut physiral 
e.OtaufttiuD, hunger aud ^loaure to L-oId may aUo 
reduce ualurnl ri-siatance. reetiloneo and Jamine 
rifti-n gci linriil in lintid, 

Simtlni'ly, inmiuiiiiy lo to:(in» uimally l» r^la- 
tiv^. At an tlhigtrntion of natural itnmunitv 1o 
tcixina, the following table wrves R gootl piiqiniw. 
I'lic hovBfl j« Ihe aniriml of ffreateat auwcptibility 
to totunuB toxin. If Ihg minimum fatal nmcunt of 
oijfi grniji of lior^e weight h taten as a unit, thi^ 
acnle of rcnBtanco for doone other animAla ta 
*>bliimtd (Knorr) : 

F(Pi I irrAm i<f K«i!hi<n-i'lif Kp^iflit 2 iiu1> tn> fkMl 

Fvr 1 <fwn t*f ettit v^ii^fit < imiS nn 'ntftl 

For t frnro (■' iDixjtc H'tltflit . . . . niLiifi? dTv rpial 

tin 1 crtm <if iptibiL nnijilkl ,. . . ^ ^ . , 1^,U0U Linit? art fiiia 
Vof 1 KfBiniirrihLclrptk Tfni^hl., ,,-,.,. .Vn^mo i]|tiT« nrf 'Mill 

III viow of Uie high immunity of the chicken 
ngiiinHl tdufiij^, one may be led to eiipposf! Iliat its 
wruifi would conlAin n Ijirge omount of actitoxiD, 
yei exparinient« show that it posee^sps praetirally 
no tetanus nutito^tin. This fuct BUggeala that 
thero 10 e. distinct typo of natural immnnily 
whirli, it is thought, mny \w indepeodent of both 
the antibadsrial and the antitoxic propertice of 
iho hody. 

It is now thouglit that the toxic elements of hac- 
tcria ore chemical ^ubstancea (very complex, 
surely) which aro able to injure the tissuea, i. a.. 
to eatjse cllseniic, only by i?ntrricig inlo chemit-al 
nnion with aubfitancea whicii the coila contain. 
Such (!liOJiii<ral subatance^ <*r groups, p<?rluinii^g 
to the rr]]*, will br ix-frrrorl to later under the 
noiBO of cell recoptore- AccordiDRly, if the cfllla 


9f in wiT-ft*' do DOt poeaess groape or ncepEor? 
v^iic^ w dpAl^ of fonoiDg ft cbonkat union 
vich tiae toxin, tbc Utter «t>old be aoftfale id pro- 
dnee injcEj. i- e^ tbe uiimftl voald be imTnone 
eroi in tbe ftbesm of flil bactericidal or aatiioxic 
pn>wTues. This coiiditioii. bowerer, is not <mc 
which IS cmpable of sftti^factorr demonstration, 
ftl leut at present, but tbe conditions point irre- 
siftiblT to itfl existence in some esses. 

We are accordinglT led to the conclusion that 
immnnitr to toxins is not in all cases antitoxic, 
in die sense that tbe aemm contains demonstrable 
antitoxin; and likerise that immunitr io bacteria 
is not in all cases antibacterial, in the sense that 
tbe wrom contains substances which are abte to 
kill tbe bacteria in test-tube experiments. Xon* 
suscq^bility and i^iagocrto^ may be of impor- 
tance in resistance of this tvpe. 

There is another factor, however, which may 
throw light on the type of natural immunity just 
consideTed. We know that tetanus toxin causes 
tetanus through its power of uniting with the 
nerre celZs^ and we may consider that tetanus is 
a Tery fatal disease, primarily because of the vital 
natu» of tbe tissue which it attacks. Now, if tbe 
toxiu, instead of uniting with the cells of s vital 
organ, were to combine with cells of less impor- 
tance to the economy, as, for example, the cclla 
of the suhcutaneons tissue^ it is probable that we 
should hate no tetanus. In some of the lower ani- 
mals there is reason to believe that the tosin of 
tetanus does unite with ^uch tissue (Metchnikoff ) . 
Roux and Borrel believe that the greater degree of 
immunity to tetanu3 which the rabbit hn? over the 
guinea-pi|! is due largely to tlie fact that the rah- 

bit's liTcr h Mc Xo fix n grcttt deal of the toxin. 
And MetduirkclT bus found that the liv«r of Che 
ircorpjdn^ w)urU ho* nn abftolute immunU^ to tet- 
aniif, absorbs the toxin And rctain^t it for months 
SBmufirj. \^Q may, thm, t^rtMwt^taie the fdllowmg an the 
Jtt^:tur^ wljicli prubally are reiponelble for Uie ^if- 
fcr«nt grftdcB oi nntuiul immunitj and tusccpti- 
hiUty to v&noD« bodmn nnd th^ir^toimii: che 
bactericidal anJ Antitodc powcia of the fientm and 
plaimn: the ilestfjctire e^iectA of Uie pho^yles 
and other ccll^ or both bacterii nnd toTiirs; a pC£- 
giblo obeobto non-suecc^tibility in sootc cases (the 
abttolute non-exiatence of ^LiiUble t^lT r[<oep1or£) ; 
Ihc Uck of siiitnble aTaikble food for the micro- 
orgsnijsne m aom^ indaQcad (atreptic immunity: 
H-n tlii^ pn-rediiig Hiapler) ; thri iwc-rvhiflmiiig dift- 
iributm of tlie *'fltiitaible" ce]l rectijitom in organs 
of iwB viul net^efitity for the indiyidual, thus 
div^niii^ tl)o poijM>ii(i frt>ni tlio more imiwrtant 

This knowteiJgc is very general, however, and in 
many ap^Jiic in^tanc^s yve continue to he in doubt 
rt'^aidiug lUe eiaot conditions which are reapon- 
fiblo for nalnrsl iramumly and iu£oeplibility. We 
hnve no rL'ii>^n ti> [lelievtr that any one fruior itt 
operative for ail iDfcoticna, although phagocytoai? 
appears to be mon^ general Id it« aclicn than the 
other proce^«s mentioned. Eadi di^nse iiiu&t be 
studied «^ a unrt in relation to each species of 
animAl, In one Inelanoe Lhe r(«i!itanc« or suaeepti- 
bility mity depend on th« bactericidal power of the 
body fluids; in snolher, on the g;i^rinicidfll action 
of ti^e leucocjl<'S ami nther cells; in anolhei", on tlie 
antitoxie (destructive) action of the cells or fcr* 
mrat? with or irilhoiit thp presence at iTiie *'iinti- 




toiina" in Uie wrem, «t^ Th«re la roaeon to 
bcli»9 that ta'o or mont Oift^frviit protcirti^ro pn>o- 
cuea may o3iae into op^rjitioD at the sonio time 
Aj[tiiUit ft fitvvn mf«ctioii. 

B^gariirig rkntiirsl nntilmic immunity^ it M*irmii 
probftblfi that wt fiftvc no example in which 
1Ji« roittftDce can b« uaiufA^nly explained solelv 
by Ihe r^imnlilj of "nntit^jiitiit'' whidi arc dcm- 
cikMrablc u) tho Mnxm ; ratlicr ivc muft neeumc the 
♦xUtence cf o^ber neaos of deairoying and r«siet- 
ing toxini, « Toentioncil ahore. 

In order that ci pathoicvnic orjfaniMn iiiar pro- 
4oc« a progT««£iiv1f fatal diAeaae in a euBccptihte 
animat, Ui'* follriwing nhnlni'W jwu^i X^ niir- 
tnonnttd: Thr tElroQs defenitcu af the hot]^ ffur- 
ficee mnet SM be on^rrome ; a local mrlamiitatory 
rwctioD vhich mar have b«cn excit^fl mn^t tlra; 
proT« )U«ir to lie inaJdjuafc for the iLinitation of 
tiM infcetion; there miutt be an iiuiifficicat vtipplv 
or insufflciint aotirity of antimiorobie and acti- 
toiie pT P c ir i wt in 1h» body tlinilB and alia, 

Oiiio' pTttpcrlits of Sormai SeruiriM 

In addition to the bactericidal ftnd antitoxic fte- 
ticiD of rnnny onnnnl AcruNit, thpv oft^n poaseef 
olhfr chjiroctcriatic* which we of the hifrhent in- 
tCTQBt in the ttndy of immonity. In earlier daj-i 
it had been notcil that Lhe transfusioa of hlond 
from one irpeeioi to anoth«r vfHB cfton fatal to the 
injectcvT sDimal. l^ater i n vast iga lion B ahotred 
that this woa dae to to^ic !<ubfltancci id the tran>* 
fn^ blood; iubitance* which agglutinated aod de- 
strojTd the Tod blood eell» of the tujected auimal. 
The proc<«a, in whicrh tlie )LcmO£lobin ia diMol^cd 
oat of the lyO blooil cvIIk, nay b« r«pnx3uc«>d m 



t«8t-titb« oxpcrimontHi by miiiEg the blood cells «^f 
0tt6 onicoal witL tho aerum of Another whicli it 

U>xic (0. c;^, rabbit Mood -|- goot serum). Tliie i^ 
li\a pTiimniiieDun oT hemolysis* and thf! nppfflr^iara 
of 8iich a ti)l>c is cvocttj like that (ecu when b'ooJ 
Ip mixed with distilled wfller or even witli tnp 
irater; i. e,. it ie a laking of tlje Irloc^i], it loses its 
opB^ilj und ossTimes n beautiful cliorrj-red color, 
Thp wrinn nf pmctk^flllv t'very species ixkntflin^ a 
hemolytic aubBtaiice (a aenim liemr>l_va:n ) for 
(ome kind of orytlirocytc, 
Cn»iAsiii4. Some Boninis also contoiD toxie agnnts for oth^r 
cclU; tlipy nrc generally cnllecl serum cytotojring. 
The s^rum of the eel not otJy contains a tiuJ:^.: 
bc'tnol3-(in, or hpnififnxin. btit also h powerful 
puLHOit fur nevvou^ tissue, neurotoxin. Similarly 
wc hnvc nonn*il leiicoloxin* (or leut^ocytcs, rephrf*- 
totifu for kidney tissue, etc. 
A«aUtlalea. Aimtlier properly of mjtny normal senims is 
thnt which cfluaca ogglulinQtion or clumping of 
baeleria, m one a«» it iu tlie Orulier-Widal test 
for typhoid. Even normn] human £crum may ag* 
^lutinfite the lyphofd hftcilliu, but to a less de^ee 
than that of a t^'pltoid patient. 
rrvvipjiisB, Onu Kvruin ofUn causes a precipitate iu the 
«cruin of another animal, or in a hacteTial culture 

Id many inetance^, a foreign scrum vhioh I* 
not particularly toxir on first iiijVclinn, bwi:»me» 
Tory poinonoufi when adminietorod (euhtrutan^ 
OMnly) a wHTiiid time (See "Anaphylasie^"» 

In cooaidcring tboie fact^ one becomes con- 
ecions of the great complexity of that eubatance 
which plnva ko LEnportaiit il |>nrt in immunity and 
it" atndy^^i. c. the blfiod Kmnii 


Acquired imniuivitj^ may he eitl'ier aotite ut [eba- 
tirt: active when it atist^s as il C4>iie*cqucncc of 
InfectiDR or artificial immunitation (vAccioBtioo) ; 
psnivo, wben piolectife or cureiti^e wi-ums axe 

Ooe who hu rtcownni from Kcarlot tame, amalU 
poff, plaguo, ^boid fever, etc, b«coiiac« pos^fAsed 
of la^ng proteodos ogaicft siahnqtient aiuc^k^, Oo 
llu; fill*r liHiiJ, Uk* iinniutiit.v nifTinlfHl by nn nU 
Uck of certain other dieciuca usiiolf^ >» r>f ehoflor 
duTStJon: chokra^ diphtheria, pD^uiii^nia, etc. So 
far nn known, llic iKiiuirnl pioWti-in ik i^piTil^i^ 
in duractcr: that is, a periiOD who has had mca»lca 
may itUl linvc Murbt fever : or an attack of diolcrrn 
iluv not prokii jiKHirut a Inli-r uttnt-k of typhnicl. 

In a number of <1ijKvi.)Cfl one attack conform no 
f^vident protection Af-omst A »TCond: ^norrli*a, 
inflttflnUi rocunimt fev^ and malaria. Snmt» dis- 
MBM may create a pr^kpoAition for ri?cnrr^fice: 
Br>"?Jj»tflKfl, inlluvnr.aH iliphUittrU in wmie iusUiii^ea, 
althongh a nilural euAC^ptlbilitj oF tlie individual 
may exj^loin repeated attncks. The were tad of 
r^corory, bowerrr, is eiilEbt^nt evideaca of at Lcaat 
a teinparary immimUy. Tt in ovi^eni thrriefnre, 
that among tlio rarioui infectious dmeaw^ diffirrent 
gndoi of flctivo immonity w.m^ he rcr^^gnized. 

Cortatn rhronir diM^UKcii ari? of imrtii'ulnr int^N 
est in thia conniHion, aa poinUd out in Chapter 




Vn. On first tli^nght Jtwoald wem thvn iiiimun- 
mH4»* ilj call have no plact iu an iofectioa of long Uura- 
tidii, from wJiich rocoi'sry in riiro or ^oea tioi oi'cur. 
ThiB, howrviT, i* iint upc^iieBnlv true, anJ Mi« vecy 
clironiciT^ of the infection may in eomc Jnstiinc^ 
d&pend on the e^lalfishment of a certain dojEre^ of 
acquired iminunUj. It I^ of courK, powiblc th^t 
in oUici' instance* chronicitj depends en a lov 
degrw of vimlrnfR on (Jit part of the mitrrci- 
organisnia or a low untural suacefitibility on the 
part of til* host- Sleeping ftickn*>aft mav Iw taken 
nn an vxamplc of a chroinc ili^rafc, th*i pfnlni">jp"l 
cour«Q of whic'h, in all probobility, depends on thi^ 
formalloD of protective aitb^tarcee. This is tndi< 
catcci from flic- fad lliat an ncuie is follow^ by a 
chronifr gtagv. At the hcigltt of the aculu tUgo 
tijpanabomeA arc very numerous in ilie blood, bnt 
after a timo tbeir number dcor^asi^ and ovLmtiially 
It U (ItfTLnilt tf> And theru e^i'Opt in or^HMH wTiioli 
>cnc af rP*crroir« for them, Ehrlirh Epcwkn of 
thie type of immunity as Immitniic non sirrUi- 
atunit, Tl may (lisjijuiHar tnmt^ or Itss completely, 
it* diMppcnrance being marhed by a recurrence of 
aculo trypanoeoiniflsis. 

The t^iatcuce cf this temporary imniunily to 
tTypanoeomiwia vtas demonutroled in nice by 
Franlce. Wlien mice, infected with mal de padorafl 
{a variety c'f t»y|iaiioeoniiasis) ar<- given an injec- 
tion of a Huflicieut <jufintitj' of "trypanrot " all the 
IrypanDWimctt are killed and tlie euro ia immediate. 
If 0. tmalkr quaDtily uf "tiypunroh" in inj-vUd, il 
mar (till be euflitiont to frfic the circulation from 
para^ules fur Iwi-rtty or thirty days, after which 
general itvaBion again occur*. During linn prrio^l 
of ctnnparativa freedom from paraeitea the animaU 



ar« r«latlT«l^ immLirr, wliich it thowa by JuAbilily 
to reinfect llieoj with trypanoftomefl of tht aomc 
ipecler. AiUr ih\i {>eriod ia piAi^d t)i«y succumb 
wry (]uk'klj, Thnt Uie lieightr!Hi*l re^blArit'i; ia 
not due to the presence of a rfleicluum of "trypan- 
roi" In the body ie shown by the fnct that nmw^pti- 
bility tor oilier apecie« of tr>pazio0OQieB (4S 
ttOj^Ana) U retained. In oth&r wordd. Uiii: tem- 
porary immurjiiy is eomettlint, if not nWiliitrlj, 
epocilio. It piobably is broug;lit about by rapid 
active imniiiDiialton con&e<pient on the di^integra- 
tSon of mnny paranitea following the adminifttro* 
tJon of th<i "trypwirot/' 

The (xiDilitioiM in sypIiiliB arK) piroplaMnofiis 
voold M<-m to be nimilnr to that in slcrpirij^ side- 
nofii; i. t., during and following general invaiios, 
reinfection from without ^oea not occur* althoiigU 
tho di^oaee i^ atill active in tome part ol tlic body- 
fa both aj'phtJS* iind try|iflD<»fivEiiiHMiK rcinvnidon 
from within may occitr^ prcfttirnAbly following the 
di«appoarAiir« of the toraporary Tiumunity. 

Tn kLiII another iuffL'tJort, rRl[i|ning fpTpr, it 
vouJd socm to be iimilftT to that in aleepiug tick- 
ud rvinrsfion altomnto hoforu tho coureo ia com- 
pleM. It Is not c^lear nity tliQ mivrD-organiKmn 
Are not entirely killed off duno^ t]i« periods uf 
tenporar>' immunity, Scvorftl factors may t>o 
involved, Uirring Uie periods ^f r^mifliinn the 
Hpirilia Wvc tlit^L'Ccmi circulatiun ami ate found 
in »om« of tl^? foltd orgOLC, particularly tho spleen* 
At thU lime tijoy mjiy bt protected to «ime dpgrc* 
by ttt\ txistemc in m^*niiH ahiidi aie K'Irtlivi*lj fitc 
from germicidal agents. Ihiring thi? period nlm 
the Iptfl Tttiataot orf-anidina nmy be detlrcyed and 
thcMw uhirh rtinnin may undergo a[L adaptation to 





ttw protcGUre nancies of tbo hart, vrhich would be 
oquiiiiloct to an inkmuDiEatioii e^aiost tli« >atj' 
Lodi<9 of Ihv licMt. The r^mirm^ctf (if gOttxtA 
inrAjion mny aUo coincide with a diMippcvnocc^ of 
the grnprnl hl<i™l immnnitT. 

ConceTtiirg mi^1» chronic infrctiond EhrlJch ina)' 
b« qitot«d ("Ch«jmotlicTApcii1i«chc TrrpaDOcomea* 
Studirn," Bvrl irfi-i, HVAwr^r. 190t'. No, 9-lS) : 
"In «croHADc« vTtfa the TJewfl vhlch Hobert Kodi 
hM developed i^gtrdin; nalaria, I awiuDe tbit Eb 
niious |kToto3K)«fl duw«BC» tD innannitx of penno* 
fiptiit etiATtcUT m far fronn occarrinc a« rtadilT a« 
in Um iD^jofilT of the bccifrial ducasn. and that 
• eotaia deem «f p«raiai»Bl ironrnDitr, cbaTa6' 
Mri»d by tlie pctMsco of antfbodiea, Sa obtained 
ovIt after pn>fonif«d inranon of the bodr, dtanand- 
uv particiUarK a lar^ number of nmmiKOa. 
If the imnunitt attaint h not enffidrot to 
dertnij <U tbc |>a^l^lleA, tbooe wbkh rtmain 
iMewMdate IfceiaMlvca to the injurioiw aj^ntv 
VQMB afv preMOti 

It baa, UKkcd. bdcn Rtf^yrvtcd that a ptneral 
ftiaaple iwtvaiU to tbe effoct tbnt anj infectioci 
is vUdi an attarfc conf«rc «traog and Uiting 
nusunitr awC be bactonal rather than protenaB 
■I ite ctiolocT' '^^^ ^^** >^ inplj, of covnai 
ttM an bodefial diiaaaae M«ftv atMg inanari^; 

ftov a*v navj ouMplm to the cMtnn, at alienor 
aMM, ahkasgli a aalfirMil anaaber of aaMpta 
ai« feBon to tattdo- it of ^tK^fBdivt Tain* in the 
ftnrij atf iioiasee al aobwn etiahgy, 

A W7 if U«t faelar f^ Fr««ma ia tttifi- 
«U EHBittulT n& tbe koovMco t&at 
^tmk of aa iBfectka (aeaiM 
I jK fci r i. «wllp«> MT bo <«ck«t fa 



iniinunJtT. Surli Hfjlit flttjirif» an? frrqiicolly 
ttoCed «poradically and in epidemics, while oci;*- 
■iontlly itti cpidi-iiLJo i« mild in rhanicLnr tbroLi^h* 
out. Epidemics of bonjgn ^mallpaic occur fre- 
ijueLU)'. lu U»L'-i? iimUiicet] it BttiiiH pmlmbli' Ihat 
the milii charaet^r of tha clincnu dcpctidi oa the 
low vini!*n*^o (>f Ihp stniin which Psittti^R the infec- 
tion; and tl^e cccdLtioD au^geata tliG poaeibtlity of 
arlifidal ntt^DuatioD of virulent n]icro-or;;aiiiHmft 
for the intijitiKe of iiiilinnu^ nl will infiK^tiiinsi nT 4 
bctii^ni rhniActcr. 

It might be po^eiblc so lo modify the vinia tlint 
protection caM be e^tablithcd without ai'lUng in 
motJOD the acluak ^iecubc even in & mild form* 
An ftttCQtiation of tliie nature heA long bs^^n prac- 
ticed wiUi *maTl(iox viruK, Brfori* rJivpox wiin 
roaorted to a« a acurce of laccinc, it had been the 
cuatotn to inoculate Uio gnnumu ^inii: of dmallpo.t, 
for the purpose of producing imiiturutj. Con- 
trary to the uaturnj expectation, thi^ njcthod, 
infltofld of repr^jliicmg nevcro amilipoi^ often 
cttusnii ihi^ [iioiHiiwl diri'Hw ("IleiJ v^iriitlu iiwini- 
bta. This phcnotncnom may depend on the fjict 
that tbe virua finda the ikia and itib^'utamouB 
ttivuc an unfjivomUc medium for Uie devclo^jmctit 
of nraJcncc; a condition which would be cquiva< 
leat t« an attenuation of the microbe. The potho* 
gefiicity of the cholera vibrio fi> Hnirnal r^pcn- 
TO^nta IB ufTecled sLmiloriy in suWataneoufl mjec- 
Uona, It If now ^nerally confidrrod that covrpox 
is smallpox which ^ihh itufTetcO a dccrebae in viru- 
lence becttuio of ita poMafrc: through tho cov, 
Conpse^mTtly, wbec tJ^Js weakened yirua ia ptiirit?fl 
in tl>f> Akin of msn, wbi^n? it rnny trndcr^o fnrtJior 
nttentiatjrin nnd prndtiro thf? nnildf^t p'T?8ibfo form 



iNyEvriiix JA7J fymvxtTY. 

of inrxlifiwl HimllpoK, wo liHv*- an Uhm] vncHnft 
In a similar mnDncr the virulence cf tlic ftnthrat 
biicillus for ebeep may be Icea^nod by pnaging the 
nrganiarn (.hroiigh the <love. 'Hiib tnotJiod of de- 
ereafiuig. f*t in some cases of inc reusing, tlie \irj- 
IcDou cf u mkrc-or^.tiii^m was reforred to tn Chnp- 
Ici VII uinVr "|tf?*iwige/' 
«H»Hiin. No single method of altenuation is suitable 
for all orgnniems, Pneteiir found that culture? 
of Uitr 1>Hi!ll1us ot oliieken-cholera became so wt-ak- 
vncn} v'htii oxpoeml lo the action of lifflit nod air 
thnt tliry mny snMy t* iiserl Jis vaccine; nlao that 
the anthras bacillus when gromi at 45' C- ib ol- 
tcnuntcd and <Tocs not form ffpores^ and coneo- 
ijiipntly tpcnmrti a =;iittabl** I'Rrrint' fi^r shocp iitid 
cattle. Of Tio !«» ink^rest to mg ia PA^t^ur'^ 
motlkod of nttonuaUnj; tlic virus of hydrophobia 
by dp«.icpating the spinal rordfl of infeotcd anU 
TDaTfl (rAbbtlQ); Iho ul(c-i-cd vinm is tlion euitabli; 
for tbo immurmition of individnah who have 
bec-'xi bittrii by a rabid animal- 
Work of the pafll do<"adc has idiown that siio- 
c«c«rul vacciualioQ ie posvtblo ag^in^t choleia, 
t;^pboid and plagiR' by (he inocirlation rjf avirn- 
leait cultnr«> or those which hare been killed out- 
right by h^at In eo far a« wc know the immiinity 
vrhii'h fn i^aused by vaccination nr proltttiVR Jn- 
oculfttion is antibacterial, or, heUer, antimicrobic. 
This point, however, is difficuH to dotc*rmine in 
relation lo ilifpascn rf unknnwn Rt.ioiogy. or in thr. 
evcnt that the micro- organ ism doe^ not lead itadf 
to the nflp^Btary ewp^rlmenTal mflnipiilations 
(flmaII|>oi. hydr^fpbobia). It \s p^imiblc that tht^ 
pmUeUoD may b<? largely Antitoxic Jn aomo 
inatancca. Tn Wright*^ method of Ihe tli^rapentlr- 

UlSitUSf !!t ACTtVJS iH^CifSTT. 


ilMcmUtion of killed culture* or bnctcrial |>rodiicU 
(q. g., ftaphj^lococd, tub«rcii1in) th^ ntt^mpt 19 
dofiiutelj made to inaea«e iht op«onina and ctlier 
ftiktibodi<« 3XL the pattent'o bLoc»d. 

O&fi may a^ if acquEred immimity to bacteria 
*nd tc li>xiri« )» dii« to th« pr««enc« of ihr: jmti- 
bacUrifll imd fiatilonic mlnUjieca which woto 
m*!nlirir*wl in ffrnriivtifln with riiturfll iTnmiinitj. 

for the i^hoi<i bAoilliifl, the ^niin i>f one who has 
rpcnvpred from fyphol*! fever po38^*5*?e tliis power 
to A mnrh prrntrr dr^rrr. A* tliis is true in iimuv 
oUltf baclerlLLl infc'ctioDe, the nt^vv i^eiefance U 
bold to depend on tiic increase of bat^lericldal suh* 
sUncn in Oi* neruin. Similarly in at^quireil Sm- 
munitT to diphtheria ncd i^ telanua. the nio^t 
oonapicuoiie ch£nf*CT \& o f^^fit tncroaec in the cor- 
refpooding antitAxinfi. 'Hi^ rostvM \% thn Mnme. 
rf^Brillr-'5 nf wlirther Ihc initminjt;ir be produced 
bj ■ oatuml .ittdck of tlie d]^jir«» or b> ftrtifidal 
immimitntLon vith the speoiflo miorobo or toxin. 
Accordlng^ly it seems prcbnble that acquired im- 
mnnity in ti^ee inntanoFB i]ppeD<U on the pr««enc9 
ID th« ecnsm of an incrrajiod amoant of propcrticii 
which, to A ccrtj^in dc^co, may bo prcMnt nor- 
Tnally. On tho "ih^c hnnd, aofjutred immunity b 
not always refireftciiletl \i\ wn inciYai* in the bac- 
lericidaL or antitoxic power of the 8cruin. Bac- 
t«rioi']ft] Antibodi«« may, Inde^, be formed, but, if 
«o^ itip mirtn^rgitnisnT^ onncprneii nre not btis- 
cepttble to thfir nction.^ Tfii* i» tlir cjik with tlw 

■tfUlnvd tatv, ir fau Inaud b««i) nboirB ihii (Nrtrtlcutr tU 
Vr0uiliiu» fti« able la r«iiK' Eb« iurmiillufl uf Atfur ejih of 

Tli« acrsH 

111 A«F|lT«> 



ttifBOTJON AUD sHuvmtr. 


ftr^ptooocco^ sUpb>'!ococciiV fii«timoeoocu^ and 
ttvfin] others. 

It vts ttftUd in tlio eucboii on natural iiDinim- 
ity tJiiit the leucoojbFH, EUiing ns phngivytes Hcrl 
&e reeorpUvo ceUn. wem to be reapc^naible, at lenst 
in purl^ for natum) rm^Uoen to an infot-UoDi and 
llierr IK now uo itttk of <ivi(l<iiK'i? tj show l.liat llicj 
arc ol grcftt irijporlanco for ticquirod immuni^i %X 
jeaat in niAry inBtances. Particularly^ Metchai- 
koff And htfi followers have provtdctJ tia villi many 
obiwrvfltiori( vhich go to prorc thi^ pcint 

Tliece inveeligsfors sliowed lliflt in acqiiireil 
immunity the phagocytefl havo a much greator 
capBt'ity for ingesting und killing l>acl«ria and for 
absorbing and dtstro.ving toKins than when the 
animAl is in a «tHt4 of greater fiisceptihility. It h 
al£<F (viTii'liiflird Lbjit lliv Jteruin \u ai.'live iiriTiiutiity 
owes its new or more powerful nnt: bacterial, nuti- 
toiic and othi>r jiropjtrti^s tt> tbo lenrocytns, irhioh 
undei the inlluenc*" of ibe iofediou liavi? fjit>du(fe<l 
the^c- Bubatancct in cxcou and excrctcsl them into 
tbp pljigma. 

The riews of Met/^ht»ikoff regarding tlie impor- 
tftDcc of phngoeytotiiE have been greatly etrenffth- 
ened in recwnt ypani nn 41 ronsequeTn.^ fif (jiinntitfl- 
tire ntudicrt of pUa^cK-ytcwis in vitro. Aa already 
Ktfttctl, phagor-ytoiU of bacr«pin depends oa their 
flnt beiii^ "aen«itiza)*' by tlie nfi^ionlna which are 
present in the jerum, In 181)5, Dcnys and Le 
Clef diJmoniit rated that the *tnim of aniinah 
vhJdL had been inimtmized with elreptomrci 
induced a much greater pbagoc.vtosis and dc"tnic- 
tion of Ihcsr orgnnisms thun normal soruiu, deter- 
mining their reanlt* by means of plat? eultm-K 
and jiiii'^OKopic Ktudicii. More rti'tutly, by means 




of the tecbaic woli^d by Ijinilimiiti viiiil hy 
Wrig:bt, thia principle b«a be«n fouud to lave n 
vido, aljnort QDivcml opplicntion : in oth&r woi'ds, 
active immimbatioD, as in a ualuml Lnfer^tioD or 
}>y the mjedioD of bacterial cells. Is nlmo^t luvAri- 
Ably occcmpaiucd by ilIi mtri^jL^ lu ojidoain^, which 
tppeare to coincide viih «n incrcfue in the phago- 
cytic power of the blood. 

Icannuch b5 it bna proved possible by Ihe pro- 
loig;cd immnnrntjon of anirnAU with baclcHa or 
tfttiiu to Fnducc a high concentration of rnitibnc- 
terial or antitoxic subAtancw in tbi^ir Kcruiti, it 
vaa tb< natiirnl r;^pcctniinn tlint if mah j^ctuiih 
wcro injoctcd into other luiimiU tti« tatter vrouLd 
therrfiy be endowod with an iiK^rease^ nwisUnc^ 
(o i}t& icifectJoua agent agajnal wliidi Lb<< sumtn 
had special activities (paesivc icnmuniKation)^ 
Th^ hoj bocn foaiid to ho the caee with mony 
antibnt'lirriiil (tjphoid, cboltrn, phu^w, djEenfery, 
etc-) and tome juilitoixie aerum;* (Oiphtheria, teta- 
auf). Unfortunately the |.<rotoctio]i affordefl by 
the iDjecliou of au iiuciuce «erum is of aliort dura* 
Uon (from two to s^eral weeks) ^ it is as if a for- 
eign aubetanco bad Li^eii injeclrd. the fate of wbcb 
it to be eliiniiiatcd rfipidly. ThU U in contrnat 
to the conditicu in acti^^ Jriimuuitv, tn wliidi ttie 
protective ■iibrianccn arc often forircil over t Joog 
period hy the b<>dy coll*. 

Tbe school of MetcbaibofF hiing» the laacnryt^ 
into relation with paMivc aa trcll fie active im- 
mnnitx. T1 in hpTd that the iinmnii« serum which 
is iDJecbtd ia pot<<nl» bccnnM; it tlimulatcfl (be ten- 
co^tes to a (prcot^r phop>cjtic actirity ia Ihe caae 
of antibaHerial fmmnniij, or tn a grmt^ abaorp- 


In |*AH*1VC 



/.v/'j;cTJO,v A^D hHitvitvn. 

m And destrui^tioii of toxiDfi in the ca^ of anti- 

lio im muni 1 7. 

"»iihuiTft«-' It i« DOW hnowD, as tUtc^i^ that nn iiiimiiiic 
i4 opi.»i>in-. pprujji favors pliagocvtoBiB becauao of it* act'on on 
Uie Imrlt^rin mUira- IJion uti the l<?uctH'vfes ; Ijerii*- 
the poajtion of Mctc'nnikofPs "Btimjlina," which 
wfirc giipi>o*^ to stiTHuUtc th* lcnci>c:ytcs to ftn 
incrdaaed }»IiagQc>lo«i», does uot eeem to b« ou t 
I^Dod footing it pr&iont. The vulue of Uie opsonins 
in jmitsivp immunitv in, irnW), nil unknown fac* 
tor; Ihc qne^lior is hardlj (ictcrmiacd finolly. 
Some of tiie opeoTficB deleriorate ven; qiiicklj; 
liciire Ihc.v coultl hi; of no voliip in serums aa tJiej 
nre plni?[''i on the rinrki-t. Otheii; Jirtj moro rceiet- 
Bnt, anfl may hnvp n rpHniit vnlnr in jmwivF imTnii- 
niKfltion. nltliongh they prolalrlv do not upproxi- 
tiiAto ID iniportftnoo the bnd^nHdnl and flntito:cic 

By way of summnrf we mo> soy that bacterici- 
dal EQbHano&a, antitoiinn and opKoninii are the 
known urn] demon stmbk* farltrr^ in m-tivr^ immnn- 
i^. It cloc« not follow that all lhrc« factors come 
Into play in every ooncoivabi*; Infection; or that If 
tlicv do. in toiiji? particidar diftease, the three are 
c<iuully important, ThUf, in typhoid fever, the 
ROritm had an enlmnt-ffd bactoricidal power, and 
invcsti Rations #cf]ri to fthow Lliat tlitf opaominfi are 
aJao inereowd: on (hii othi-r hand, m^l? hav^: no 
flvidence to show that a^^quired immunity to 
typhoid fever is antitoxic. In dipbthtiria and tcta- 
Bue, the Jcnmnnity U ropro*rented by the presence 
fjf ixnl[iL>xinw in th* »rnim, whnrrji* tho fip«nnme 
ond badtrioU-pins appcnr to be *>f Icwi importanoe. 

Anotlier coodition U found in infixHione with 
stapliylo<:occJ, fctreplococ^d^ pneumocwci and mm» 


HXmtV Alius JO TOXtSS. 


oihvr or|^&Di«inAr ld whicli the onl^ dGnLonslrab^ 
cbaufco of impt>rtan(-"e ia on iDcrcaAe in Uic opa<»' 
nin*, Dud witTi {U\* nn iriLTvaftv In (tie power of 
phi^cytic dc«truclion of tl^e coccr 

In (omc chronic inFetTtion* it is poMiblc that thp n«wt»a<u».i 
inr^ividiial Ahoiva n i^istnncn to the bnct^rifil 
toxifjii, wlitL^]] U on tlic- order »f liabihintiou, or 
odApIation, arid whicli ia not roprcsontc^d by 
itnjr i3i-moiiiitnib1t* antitniiii«. Thui, bj tlie nw- 
ijf ^ruilujilly i^cre^^Iij^' iIohu iif tiibeiiJuliD. an 
individiinl mny cvontunify tolcrntc Ur^ doict 
vhich in tho b<?;^inuiDg woald have bu«ji ^ur^' 

In fpite of tbifl acquired recistancc, however, 
the bod^ appears to fono no true antitoxin for the 
tobarcnlJn.' Aft«:r tho ccuation of trofttnicnt tha 
rad»tnnce nX Uir ti]di\ulun1 gradually n^turii^ to 
nornml; timt la to ht^, the cella return to thetr 
crjginel EH^cf^ptibility. 

Tlw |joaibIe rvUtton nf aimphyU^U In ncijuirud 
iiikniunlti vill be diflcussed in fhc cljaptcr on 

Ucntion mciy be made bore of tho woll-known 
tut cniioua phenomcDCti tJiat reei^tance may vno' 
vith Ibc a^^ of the individnaL Typhoid fovor at- 
bick<i the adoTo^cdnt or middl^^gi^d ratlier llian 
Uie leij younj: or v*ry old. Active tnbcreutosie 
gf^yw^ Um eommon in the later dcy^adcd of life. 
Then r« have what arr dtHlinctJvely the dUiwMK 
of childhood : aftCT 15 >x?are of a^e diphtheria, for 
«xamplo, i« uneommoD. Some of these iualaneoe 

1£. Aofh a POiirK or tNAtnttnr dAM mm* thn fomtRtknn 
of jaTlliu4lca ttf ■ ■(K<tac <luirft.<l*r. bal ih'jr upp-Mr tit^t Ea 
b« kniaailf lb <lMr4flvr TAd "kiirtlatwmllii" vhl^it na«- 
«rrBiiiEii> rTDriiiK'* \yy mfiqim of ih* ipcdioil of ftiatlait tF 


iys'UvrtQx A^D tuiivyiTY- 

of uo<|UjrTNl immiinUy may be rcfemble (o dilTur- 
cnccji in the character of the cell reccptera at diU 
foTont *g^a, while pprhnpn olhers arc due to n *\t>yr 
immuimmg process occasioned hy tijc prolonged 
preeenco of non-pathogimic amouxite of th* proper 
Bmmr^^m, Emmcrich and Loew found that many b&cteria 
produce In ci]]tttro media, en woll as in the animal 
boi3j, rtubsUnce* winch ftppan^ntly :n:t o-s fi-rmenta 
and which nrc nbie to Icill nol only the hflctcrium 
whioh Becreteft ihe f*mn?r(, but manj' othere. For 
example, pyofrynnoAc. (lie bjt<^tcrii)Tytio enzytuc of 
Bacxll^ia pyoeyaneus, dieeolvoa pyocvaucnB, 
nntlirnr, rTiphllieria and typhnid imfifli, Oie vibnci 
of diolc-ra. tlii? tlreptocoocus and »itapbylococcuai 
TEiotfc ujjKymt-Et ununlty imq not toxio, and it baa 
been supposed that Jr tbtj coiiree of an infprtion 
lliey rt^id\ sui'li a coiii'L-iitrutiojj in the blood tliat 
they doflroy Ihc bacteria whiph produced th^nij 
thus bringing about recovery. It h asserted ulw) 
that they, cithci d«rin£ icftctlon or m a r«uU of 
r^podted injectian of tiio ffimont, cuter inxo a 
aoni&whiit ;x-nnaiit*iit rcmbinnlion with ihv a1* 
btiznin of tlie body, forming tlie so-called ^^im* 
miine-protcldina," en wliich ncquired immunity 


It i*alBo stated that with "pyCK:yanaM-iiTimuno- 
preteldfn" ft ia possible ao to immucite a rubbit 
tbttl a iiiil;.>ic!r|uctit ft^'Hvc? dfijs] otliETwi^e fntnl 
dOFc of the anthmx hacillUE is harmloae. 

Althotigb thp pfTfflMfi of thow "en/ymes" on 
anthrax and on aomc other orgnnisms have bf-nn 
conlinDed by it airmb^r of invatifratorv, their im- 
portance in acqijJr^T iiiiinenity and in tlie recov- 
ery from in/oolrons i* ver>' doubtful. There is the 



9p«ctfll objftlion to \}m theory thnt k pufji tnn- 
munity oa a non-ftpccific baais; i. c>, p^rocyacado 
will protect ftgniurt flnthnis:. diphthmi, clc, 
wliilt, in rwilUy, jill our diuJcul ttc^ ciperiincntal 
tjata point to the hijth <pccilic!ity of naquirad 

Tn fontfJi^t to tliR Hpmftc iinmiinizinlioii wliidi 
may ho aocomi>lrEb«d wilh nn fmimmo nftnjm, it i* 
imfiortant [o tf^^o^uh^ tlist « non-spiwifir incn'iiw 
in resietaiice mnj he caused by tlit iiijctlion o! a 
nombcr of *i:b*tftti<?«, winch in t1i« u-st'tnlu* hu*e 
no d*sti"Urtive nrfjon on thn W^ftprm. Ii^^nrlT 
injoctcd into tlj< ponloncnl cavity eucEi Biihrtflncc* 
«s bouillon, tabeiviilin rniil ^Eeril^ ririne, hilcI fftiiiid 
\he TttlsiATitx of Ihc atiimals jncrcajd to the prri- 
ronvfll fnociitatic^n of virulent crgflniiimM. Normni 
aeruiii fioiu anollmr aainia] hu a siiuilar elToct, 
but, in UlIa insUriEi^e, Uk' bactoricida] eubit»ino«£ of 
li«! /*)W!igii *iT]"um inny be ii factor in Llic* in?w 
rc»istancc. Suppc»cdly, lina noo-fipccitic rcMiifinncc 
la t(x^], a&d ^t app«8Te to d^cnd on tlie attractioo 
of AH itttT*M>iHl nuicjbtr tif pba^jw^lra find of midi- 
tional complcnrcnt ^nltjun) 10 the pontoncal cat*^ 
iiy. Tli(i »nggcslion that, preceding lApafotomyi 
Duddnic acid be injeLU-tl inlc ti^c abdominal uki' 
itj, in ordor to ini.'r^iLi]<; ihv IoimI i-us.if:iui}cc, has 
ita fanndation in thi^ i-xpmini'ntjil unrk nlnrl 

The semm of an animal acqulrfe antibodici^ rol |„ 
only iCT bAdtcria and toxuit, but dIm: for many *^'" 
other cHIk nnd subBtanccs which may b& iikJtK-tj?d. 
There are many immune c>'t«toxii«, euch ns the 
bcmclyitntr It^ueotoxiris, nourotOKinji, n«phrotoxina, 
etc., wbjch are fornifd tn the rt-^ult uf iiiLaiuuijoi' 
lioa with the conofponding cello. (See "Cvto- 



liiirsuiivtt Anu iuuvsity. 


(till* l'r»»i'll*- 
IDE l»r ««!**< 

By fj^fwriftUcslly injecting an animal Vfith « 
boctonum or with nny fiMue Gcl)> agg'liitinating 
«TiIii;laric» (ngglntiniitB) are formrid ond may bo 
deotonstratej in Uie Mtiuiii. T,ike otimr nntihoiliM, 
they arc hi^hfy Bpccirip for the cell used in ttie 
iitiniwn lotion. 

It f]U8 btcu foimil tlmt toxins, oilier Uifln thm^ 
of bfictGriijJ origin^ will y^old anlttoxins by ira- 
mnnixjitloa, Such tnxirs an? snJLke vcnam, jicld- 
ing antivcDiG- rJcin. a ]ii>niJi^'e;)ulinaUii|^ loxia 
from tlio ijualor-oil bL-an. m Mi ij .iTi(iri<.'ja, eto, 

Ktcrnlly whnt is ieni^i^t lii' i.i^logit? |j>*t for- 
spccice hftA ofiaumcd prominGDcc. Thia test may 
b*i lUufllrnUd: A gool is tnjt'Clcd repoaledly with 
thp spniTFi of m.nn Aft?p ;i iinmlmt of itijet-lion* 
u V[?ry minulc amount of tliis goat'a aeritrn will 
causo a pri^jpjtjtto when mjx<3<) witli liumun 
M'tnm, l>ijt not when mixed witli iTie serum of nny 
otlirr ajiimal (except, pcrlinpf, fhrit of autliropoid 
apc«). Tho toet ia w dolicato tliat vhf?Q n »mall 
amoHrit of old driyd liumari blood la diafohcd in 
*alt solution and trcnlfd with t,hc poat etrum Iha 
procipUatioQ will slill <>i?njr, and in "Afvi of thin 
fnd, Ibc l«t haa become erf medicolegal impor- 
ts noc, 

'Dip "vide iliNtribulioii of this phRnmni^ntin 
amoDf: all Tdnd« of animda j^vea it ^cat biolojrc 
iif-nificaT^ce, fmrticidarl^- hh regarde the differentia- 
tion i)f apeizie^. 

Krauii (ovind thai by immunization with <!Qr- 
tflin hjirWinl flllrnlra siibubncrs nr^ formal in 
the^rum which cauac prccipilatea in tbe filtrates. 
It \% further {nt«T«atiD^ that other albumin-con- 
taming ^iibsliinrf^, n* e^^ nlbumin or rriilk, wiIT 
on inimnni^ftlion, yield specitio flutibodite- The 



eeroni of an animal which has b^n immunized 
with goafs milk will cause a precipitate in the 
latter, but not in cow's milk, (See "Precipitina.") 

It baa also been possible to obtain specific anti^ 
bodies for ferments: for the peptonizing fermenU 
of bacteria, for eraulsin, lab, fibrin ferments, etc. 

There are, however, a great many substances for 
which antibodies can not be obtained; this is true 
for substances of known ehemioal composition, 
such as acids, bases, "alts, and for the alkaloids 
(strychnin, morphin, aconite, etc.) 

Am I f ement ■■ 



Through Ehriich the word toxin hft« cora^ U 
linvL* it wjiecial vigiiincHJictf, being applied only lo m 
certain type of toxic sabfUnccf. Accortiiiii: (o hi» 
ortginal conception thoy ha^ the following P'^P' 


1- They nrr oxtiMncly InWli^ sTibsUnti-a vrbifh 
occar as flCcratiOQ productfl oi TCgctoblc or af ani- 
itiaJ org:anianiVL 

a. Their clicmicol natiira is rnlmoira. The im- 
pQ9^bi]ity of cbfiuriiop tiiJ*iH in pii^e form anrl 
theii ^?at lability icnilor them iamiecept^bte to 
ordinary c^hcmioaE tmaEyeie. 

S. An annlvGis nf a tDiin may be readied at 
prfwiit only through the medium oi biologic ex- 

4. TmimiDTzatlon with tosine yields Biititoxin«. 
Tt haa not hectt possible to obtnin antitoxinA for 
inor^^nlc poisons, jflucoside and nltraloidfl 
(mnrpliin, ttrvclinin, cte.) 

b, la contiBfit tr> tvell-dcilDcd clicmical poiaons, 
tho aoti^ of toxins ib di£mcUri«cd by a latent or 
incubation perim!. Thnt U. frillnwing thi"*. intmilnc' 
Hon of a totia, a cortaio jjenod nf time eUpsca 
bofofe loiic symptoms appear. nin\ this period is 
grcnter thmi Ite time logienlly re<|nired for t1i« 
jibeorption of the loxin t}iToygh the drculnlion.* 

1h RtcoDt <vDrt: Indk^tu (hut the ]tiT\g IncdbAtlOD pfrlfld 

i\t tlui« rVQLilrtd <(ir IliB IjiId Fb rCkrb Ilia fqDjrllsa r«11a 
tlkr4tifh tbv Alto cjllnilFn Af Ihg motor Wrrw. 



The in mention pertoi! mny bo *lirirt*D0[1 experi- 
meiiuUl/ bj the injecLiou cf large qaautiUeA of 
toxin, but it cao not bv eliminatod entirely. Thc^ 
poboDA of fiftftlcD vftnomu np[Wflr to ad without in< 
cnbiiLiuiT [MTinci, Imi tlirv nrr *tin ti bi^ Hnunl 
with th(- tiumy, bccuuEW of ihcir power U^ cniiRf 
the fonnatioD of HDtitoxiTift. 

6. "Tho fa>eU maJcc; it BOCi^«tarj' to utuumc. as a 
ri>mJitifin for tin* poiKonoii* nction of tnxir^s ™ *P^ 
cific chemit-ol union of L?»e toxia vith tbt proto- 
p]jj:m of the culU in certain orjfjine.*' . . . "Thn 
alJlmiy of oilier poSwai. m the alkfiloi^R. for 
tiBSUce, dcp^ds not on chemical uii]on> but on 
actno Auch proccw as aoLd •otution or bona salt 

Th^ preparation of the soluble toiim of baclcriii ercpHnnion 
is r*lotii-clv fimplo. 11 ie necceaary only to inocu 
IbIit ft fiuitibli" fluid mpdinm with a rnltnrA of tbc 
microorgimisn], to nllovr growtii ic inkc plnn? for 
«ome days at bodj temperature, then to pan the 
Amd through fl porcvlain or «omo equivalent fLlter^ 
The nJuhlt Loxina ufually mnv bi' pnvripitittt^l 
fjom the filtrate by tome prccipiUiit> m aiiimon- 
ium aolphato, and pnacrvcd in a dried vtate for n 
long period, Siirh n prprjpitntp d^w uot repr*»enl 
the toxin in a pure fonn. hut rimn^ proteid «ub- 
vtancc* of tho CQltnra in«^nim, aa well. 

Tlii? bacilli of dipfithffnn nrid tetanus^ Btt^Uvt 
pj/Gcpanfus, nnl Hcnllttf botttUnju, ur? the prinol- 
pal micro-or^aniimiBi which product solublo toiina. 

When the toxina of th<«^ orfrnniema sro injected 
tDto a ituilab)r animal^ phenomena aiTniTar to thow 
prodncdd by an infection with tlio organianui 
Ihainicivo* arc proJucd!. Thin- arc in a particn- 


iifrBVTmy xyo iUMUNtTY. 

To El 04. 

\%r M'nM Jificwrilli^ tdxiDN. Some micro-orjrimifTM, 

finwftvnr, prodiK^f' more tlinn one toxiu. The teta- 
nus baciJ[uj4« for eianiptc. #r:<rrHee. iu addm4>fi to 
tho tcrxin caiuiDi* the nervoue pymploms of 1«tjinus, 
nnoOker ( l<^'^"^^Lvsiu, or teUtiiin ImTnolyMn) vrhjcji 
hnfl Uie pover to ilcstxoj red blood celb^ Ehrlicli 
holds tbnt the diphtheria bndllufl producw not 
only tlio toxia which cnusce thr nctitc lotoxicdtiOQ 
of diphUicria, but anotber of long Incnbatl^ 
pericHl whicli mny cnuai* piinilvoitt r«l>Tii p(ii.*on 
hu at leaat Ivo toxins, one which at1fich« the nerv- 
ous lJBflii«— ^ neurolojin^and onothor which at- 
Uela the cry thtocy toe ; tlio two may bo separated 
by appropriate measuree. Aa previrmsly Btatp»1, 
the serum «f the nel haa a stronj; OButotoxm and 
a homAloxiiK 

Some micro-or^^anianiB produce ono or moro 
Aoiublo tciic subfllanocfi, which it is oft«n difTicult 
or impoaslblc to {^oneldGr aa the actual dl&eaee- 
producing^ elemente of Utese orgamAiiUH Concern- 
ing a discnfe which ifi fo veil cliarDcterined dini- 
callj ns tetanus, it is not dilfieulb to dctermmc 
by inoculation e;:perimeiit ^■h<ith9r one haa in hand 
lb© specific toitin. The proof U natiirally much 
more difficult in infcctiOEs with *t[-eptococci nnd 
»tdph>Locoo:i, fcr csnmplc. in which the group of 
•ympton:* nnd tho pAthoIopc conditions aro not 
entirdy uniqite for Hit infection. We are by no 
iiieaiia cerUJu Uiut thr hemolysin or the hutaooi* 
fiiw (tosin for Icucocyto*) of the staphylococcua, 
or tho hom.>l_vfin of tho strcptococcua are tho para- 
mount disejLH'-pri.Kliidrti? tri.vina of tlicse organism*, 
although those Aubalanctt arc true toxitifi. 



An imporlimf. tratt for \he pa(t):ngrnir Hignifi- 
c&Ace of a toxin liee io tU ability or inubilKy to 
cauiM tiio fonrmtinn of nn antitoxin which \t 
cfHcicnt in the ttcatutcnt of an infccUon by the 
coTr«0|3Ofiding (yrgfinhm. 'this la uol tho ea>>« 
Willi Uu? toiins jutt nicnnouraK Howrvct, or» 
ehould not plao: too itiucli importance on bucIi a 
U«t, for it it jMi-aib]r ihat wc nrr not aMo on 
ittttflcial culture mpdin to obtain the toim in 
such concentration that the production of an clU- 
ciont nnlitom is poe«iMo. 

There 14 a Inig^ c\nm of orgam«Tn4 thcr momlKfru !■■*« 
of ifhicb apparccntly do not produce soluble toiin*; nZVi 
Buch or^ranifiris, ho vover^ cause highly toxic disMAM 
(i*, If,, l)^)lioiil, lOirilrrn^ jiln^^iii?). TUt^ deml Of 
grottjhdHip bodies of i«ch bnct^na arc very toxic; 
a]AO vliMi the g«nns disiotogratd hy n procou of 
autolyaJA or eolf-digestion thd culture medium be- 
oomca toxic bccauuc of tli4 cell contcuu vulxicii ar« 
*rt fnv Stich orpmismfi nfp usii^ tf> cnnlaln In- 
liacttlular toxins or endotoxuru. In infcctiopa by 
tiietn it i« mppoAod lliat toxic jayinptoms arc pro- 
duced whea a patho^fcruc amount of the intracel- 
hilar toxini: » libcrato^l by the bnctoriolytic action 
of Oie body fluid* or i*ll» (pliagocyl**). 

Kotking ia knoun of the nature of such tojoiia. 
They CGitJiinly nr;: very difTcrciit from tbo »olubE« 
tnj(in» of diphthcno nnd totajitu, einco immunisa- 
tion with tJitm has not aa jc4 ru*ciUed in t!ic pro* 
doction of dUdont oatitoxiDa. In >pitc of thia 
fact, however. It is none the lew probable thai 
tlicj 4JC the difcflM^producinic coQ»titueDt» of the 
orgtmnna. Bucbnor gave th^ name of *>la<miin^ 
lo the coll ji]i<v vhich h« vai able b> OTcprav from 
•one miCTo-oTgaxuvms. 

IB or 


jxravfiof^ .^^if tMvoyirr. 

lkfucFfl4l)en, hy ^nnilin^ large mUBM of typhoid 
hflfilli and other ortiariUniS whioh had been rend- 
ored britilo by Ihe t«mp«rDtuT« of liquid air, 
ciMniri*. frimi iliesi- or^niiiMfis n tojic cell juice. 
The efficiency of th* anliloxitJS whicU lie in Miid 
to obtain by such immunizaijon bas cot beeci 
drmoiiFtrBted praHirnlly. It K'cm* improbable 
llmt imniHniaftticiu wiUi such ''toxinH'* will vicld ft 
Kpniin diff^'Hng in firpnrtiM from thflt obtniDcd 
Lj iiiimuiiiiuifiou nilZi (Ih^ liti'i^ ur^iiuisiits- 

Toxic atibrtftrcttobtflinod from bacteria by the 
action ct fctron;; dii^mrciiU mid exlrnctini; fluids, 
jrmy nat rcprctfrTLt tlio cw^tial fnxiv siibi^tnncc of 
the ofganisni. lut pcrtjapa some dUintcgratioE) 
pTOduut which happens to bu tovie. 

Il it, of coLine. comraoQ kcovIeJ^'c that an uiti* 
foxrn lA the blcK>d perum of an rinimal. after tJie 
InitOT has bwn renrlprecl highly iminiinfl hy rc- 
I>OBtCTl inj«Ttiori5 of Ihe conVApoiultng lo^iii. tlie 
hoi*c is ch<wrn ff>r immimiBatJon bccnns^c of iU 
marked ability to yield ftntitor^n! (rlfphthmHa. 
ir^tami^), bpfnusr of il* r^lzn. K'ithntniidmK niiich 
loB3 of Mood, and becaiiw of the readineea with 
which it <iibniit«i to mnnipninlion, 

Mftnufficturiog plsote v)iich praduc« fintltoxiM 
ai\d otlior ajitiaorume on a !ax>re wcnle hove aplcn- 
dhlly *quipp«l fflnbles, which -iri? kept in fW 
rptimiiin hTfiicric condition, arii3 from vihkh rate 
in pflrticnkr in» rigoroudy cxclndcd.' Tho hor«» 

3, Til* lifl|«r(fiB*o of Thli I* r*fjr jir»it If, for «iiropI«. 
borKB arv rfwlvlu^ ]n|Htl«nA of umi> rlruiMi Uriwiu 
taien-orgMiiBn fiki th* r>t*cuT badUnBl^ In thU t-iui* 
ilTlnjT mirro-arffanl^mn Hfirh Ihp ffunomi i-trniZtrinri, iinil ■ 
nt hitting bttt*:t (hr vvruini couM well nnirna lb« 
rlifDt 4n<1 b* 4A ^plfT<<Tir wfiaree of daqfar. doI oqI? to 
Other BDlnidJi. but ii> iliD raaiiQunllv nt inrffr«. I^rrn Hy 
■WMf Mill* »f« phOpDflr laallrulfid Ifk 4iifb rfvni 




ir« cu^fuU^ groomei^ and nouii^hed and giv«ii 
incli ^^etvm us will k««p thvm id a h^lthy con- 

The tojtiiu, in solution, art injected mibcutane- 
Otiilj.' Gmrc iind «vesn fiital tiuictions may foltuvr 
the firft injeclioiw, if the toxin hus been givon in 
too Urjfc iIoaeH or id too concentrated solutions. 
Tlufl ifl especially true when injecting ktanuA 
toxin. It h of K^ccit importfinrc tlrst tn r^tabliKh 
what the Germaia call a "Orundimmuniidt," 
whicli meaiia a priumrj iuiHiunitv in LLi; aniiitnl 
ittolf &i> that tiic tnuBunizatioQ may then be 
puohod vi^rouAiv ntitil tbo blnod (watoiiu onti* 
toxin in high coitcvntmUom. h'or t)>U purpose^ it 
ha^ been fuuiid otvtatary to weflien tbo first tos- 
ioa injected. This mny bi* [lore by beuluif tbe 
loiin solution to 65 or 7D C. for «n hour; by aJd- 
mg to it from 0.05 to 0.4 per cent ^f the trichlo- 
rid «f iodin ; or by addinjir n lohition of potmuiium 
lodid in which iodiu ha» been dissolved (Liigors 
ftolution) or, &t is oft^n dono at prwcnt, by par- 
tially neutrali:unK t'^^ ioxin vritit atititj>xia H]|;h 
dilutions of Vhc unnltrivrl bmn may nU^i b(< iim^cI. 
Ondaally lie viruWo^ and amount of tlie toxin 
i&j«ctcd may t-c incrcaAd until finally Uic full 
Timlent toxin ia given in large dose^. The increaae 
in dongc must be \cty gradtiah l^Ttntimlly a% 
EsticU as a liter or morr of dlphtlieria toxin h 

PollowiDg each Infection a reBwtiou occur?!. 
With diphthoria the Jocul awclImjET may be {Treat, 
and ^loD^^hin^ may occur. FvDovtn;; an injection 

of Tl>klma. 



«r i#rani<. 

of 1«taiiua toxin, totuiic symptonu may appear. 
In either ciuOt Hictv w itomc lo&§ at wi^ight and 
often fevor. and another injoctti^fi Timst QOt be 
^iven until Urn original voight U reffnified ind 
the ^crDoral behavior of Uic arimaJ indicates (hat 
iU former healthy condition is re-oatabliehod. 

S('vi*rul monthit of 4iiHi treilujent nre n«'tt«nirj 
ics the production of dJpbUicria antitoxin m high 
ConecDtTfttifii]. At the end of this tmjc blood le 
drxwn from the jLgrilar v^in by niean» of a larg« 
trochAT to vhich n rubbrr tube i« atudied. Tlte 
tube loada t<i a tall gla^a evlmdcr holding from 
one to two liters, and into tliiH the blood h allowed 
to flow. SJJt liter* ua.iy be drawn nfdy fxom a 
horae of avepa^ *ite.* The moat TJfrid a£Op«is it 
iibu'TViHl iti fnkiuj^ flir blrxid, Thn g1n» fylinder^ 
appropriately coi'crcU to present coi^t^ninati^u 
are th«a ert in n cool, dark pluoe, and after U» 
Hrum has separated from tlie clot aamplcs tra 
taken to hf tmt^ for their antitoxic v&luc 

The MTiun, tn bulk or after b«injf bottled for 
tJve tmdo, ia ppwer i ' ftl At a lov t«mp<^ratnni sod 
in thfr dark, 0.$ per cent, of auholic acid luTiDg 
been added to insnn aCenlity* TliO additioti of 
th« aeid mar oauw baimlate cloudincu in tbo 
tifmnt. hut da» not devtroj thb anUtnuii. Senuna 
ma; ho pnecrrad porfccUy in a dried or frracn 

Uany facts of Fckntilc and practica] impor- 
Unce hafo betn bron^ to li^t throng th« im*- 
muniiAtkiB ol aaitikala on * larg^ Mile. It hta 

UwflL tomvtr. «■ tbUHl aicww iam vmlaabte ■■■■■» 



bom ionnA, for cxainple, that following cuch in* 
jectiou of toain the amount of Antitoxin in the 
bJood ffulf^ri a rvductjon. and only e<^ualft or naca 
aboT^ the previous auiouiit dght or laa Juyc later. 
This decrcACC it explained by afl^umin^ that the 
toiin hai^, to h ceri£.in extent, imiiv<] eiiL-mU-Aily 
miQi the circuInUug a.iititoiin. It ind niU^ al'^ 
the period at which thft horso &houl<J bi) L»Ied iu 
ortler thai tlie greatest amount of antitoxin may 
be obtained, [t mii^iil even I>e das^'^rouH Us iltnw 
tbe blood before this tiincT had clapsml. unte noith' 
fr«ti Itaiin might utiU he in thv circulation. 

It u not«7wort}iy that all horaes arc uot equally 
good producors of antit4>xia One may yield a 
KTUiQ nf i}tnv Limiw th^ vuliir of urolhrr, k.U 
thoogrh the two haTe been tre^t^d iJentjcally nnd 
aeem to bo equally Immuncf to iht^ toxin. 

AnoUiot mi^t int^rwting fact is that, altliongh 
iht blood of dti aatnial may be very lidi in anli- 
toxiik bo ffUll may haw a <liApropcrtfon3te snfi- 
eepLibilfty to frcali iuja^Uoii-i ^f ih& toxiu, 

Ala&y of thcac ^bcnomcna have not boon ex- 
plaiaod Mtiifadorily. 

The nereanty of aUmlnrdLtinjf niititoxiuit --m 
that docofre may bo controlkd acruratoly i% ^U- 
evtilent To meet this netd the antitoxic unit *"'*••■ 
faaiilUr in practice vaa dcriacd. 

Behnnu. an*! alio Ehrhcb, docidod arbitrarily 
to coiuiilt-r AA tho antitoxic unit that quantity of a 
Kmm which woulj protect a ituinei-pip from 100 
fatal ^oBoa of the toxin. Ebrlich"* original method 
of t*»ting 11 wmm wag t/* mix i^ilTpfprt qnanHfiw 
with 10 fatal (loaea of ihe loxin and inject each 
mixture iato a tTuin^a-jji;; of fri>rii '^hO to 300 
gruMa* vfriiFht. ThJit igunnlity of ihv wnim whtrh 

f Iah of T«Bti 
nqa Anil- 




protdoted tlio aniuiBl flptunst the \vi\ faU! dooc^ of 
tonn oontfliii^d I/tO of od immunity unit, and 
from thiH rtvult Uic ninitbsr of imil« in a cubic 
ceatimdcr ccutd be colculntc^. This method in- 
volved the use of toxin &« t};€ standard by vlucb 
Uit- v:i!t^e of die m^titi^iiD waa iinsa^iiretl, afid it 
wo* fount! to be unreliable, A tojcm degentmlcfi 
raU](>r rapidiy, reUining at the samo lime ita 
biiuliiig puAHT fur tlit- luiLitoxirc; Uenoe two t^ls 
niAdc with the same strruin tvro montha apart 
might irulicate diffetenl antitoxic vfl3u« for Uie 
wrutn, \Ut> 10 fatal dosr* nf fine l^iiin ofUm re- 
quirijd more antitoxin for ncutmliiation Uiaa the 
Kaui^ <]uaiHity ef a m*oofiJ toidn, Tliese pheunmena 
arc iluc to tlit formation of toxida, (Sor next 
chnptor, J 

On iLcconrit at tlitw? ituurt^eE of error^ Ehrlidi 
lieviflcd A Dcrw method iu which a stanrjard anti- 
toxin or test-^rum is naed as th^ starting point 
f<ir thi» viiluntimi of n mw neruin. The Ual^Heruni 
liflcrl nl llic Koval Pniiwifln Inatitiifc for Kxpcri- 
lueiital Thtfrapy nt Frankfurt, of whioli Ehrlich 
It the <3irwtor. i» a fined an^ pnwdererl wrrnm of 
0Qob atroDgth that 1 j^ram contAine 1,700 imoitin- 
\Xy unit*: ". f.. I/I7fl0 gm. would protwt u guinea^ 
pig against 100 fatal doBKW of a diphthrria toxin.* 

T«1« lodlTldiuli or BqrtMJnLtlont lad muDurieturen ar* r«- 
qaind t* HDd k Mnple or vivrr lut «r Hfqo lHliiii(l<d for 
Chi Ifttd* lo tb> I^AbkfurC loBtltnt* ihil Iti «»< Ttlue b«j 
b4 dAtmnlBCil, ICi'ti bottle T*<DtU4itr r<ecU» a Kamp ■!(< 
nlfylnC Ifaa nluii In ■ntlloiLa unlti af [ti# conTAlnM Hrum. 
Moninm. 4fimri1v Af ftvnr; lol nf Hrun ftr* nUlDfld la tb« 

Lsimnui. and rrfim tiw tc iimA inn** «n« mtwi ; uid trb^a 
It tt found thai (hp ■ainiii'^ liiiT^ dprcn^rattd biraad a Mr< 
Iain T«]UB ItiP o«lcr la I'lit unE lo mU In an vinim b«1aB|*> 
iDf to (li» 4liiTii*r»ti»(] lol WTibh a PJauuIaciBrw tbiAla 



Any oUwr higli-gmdc? wrutii wuuld [luvc un»wL*n<d 
equally well. 

The instituUi koeps in stock a lorf^ number ^F 
x'lal^f vof-'h voulamiiig 2 grniciR of thLs 'Iriad 
■erunt. The iiir nctd moifitiire are eihauuted from 
&iu?h vial ard the latter te tliCD Bcafod in the llama. 
Oncu in tUroo monLlis oiw of these viule U hrokiui 
o|«ai carefully Jin<] tJic wirnim dissolved in £00 cr- 
of a aolution made up of equiU pajta of glycerin 
ukd 10 por cent salt solution; hence each cubic 
ceotiiiieUu' uf IJl(- Niiliiikm contjtin-i IT LiiiiLs, Urn* 
iag the Tiiccccdicg three months this antitoxic 
lolution ifl nadd in tlte oomparntive valuation of 
new antttoxinA; the unhitioii rrtiuTUt iU i^ta-ngUi 
unaltered for this period. For indivit^uaJ Xtsta 
the aerum-«oluliot juirt dcscrihed i* q^^iei dilutM 
»i?vr-ntjwiifold, M thft.l cflch cubic ccntinirtcr con- 
tains ono unit This adds to convenience and ac- 

T)w flrKt vUip in Uif! pnvisw im bo ntjifidartiixB 
ftMue diphtheria toxin in which the dnerntTntit^i: 
chongoa (toxoid rormntion] hav-e eomc to a stand- 
fttiir This Ea done hy adding eo much of the toxin 
to i \mit (1 c.c.) of ti:e test scrum thnt an exceiae 
of one fatal doM of the torin romftin* unbound by 
thi^ juilitJtiin- 

Tho quantity nf Uio lotin which srivc* thin n^ 
ndt u «JIca the L+dose.* Th<T LO doae of the 

tbe 9tnn ot one ot b1« faonc* iMu « bl|ti taJbc ht tttj 
draw a •mjill ainmint of Moo4 fron 1h« ■nTmilf inJ «tnd 

tbe Hfun fo Prankfiirt for n urTllAiIiLiirj 1«C. If Tlii 

tfHir; II If U WH» h« vtll b* iJvtatd fo cT^Dtlnii* Ibft 

lUDBlllflttOD rot t VlOH. 

0- l«— l,inM U'lvklt) : ^ ■■ conraaBlj' om^ t« Tuill^iM 
s fatal fHnli. 


toxin nbo ia doterminod. Uiia boin;: tlio nmouJit 
ivhich J« exactly neutralized hy tho imit o( anti- 
toxin. The lue ttf tb? two dowH verves to ^Hmiimte 
■ubjtctiTf em>ra on the part of the observer. Tho 
L-f ami 1*0 dfwoja of :Avin Arc then iwod t'> dr*- 
terniine tlie voluo <*f new nrtitoxBiu. Thjit qnvin- 
tity of Lhe new wrum wliioh. wben rnfiwl with the 
L+ ttose of toxin, cau*i"» !hc- niLimjil In difl In 
four lo tin ^ays, coDtaina 1 unit of aQtitoxin. If, 
for oxarnpl^r 1/100 c^, accomphcliot thii rMnlt, 
the Kerum is of one hundredfold strength, i. c, 1 
c^c. would oontnin 100 nntitom naits. 

Ill HiTordrtnce wilh the Act aj'pruvwl .Taly 1, 
190S. tTje United States Public HeaHh nnd MiHne- 
Hofipital Service hat ^ptablinhcHJ a iftanrjard unit 
fcr thi* country, Tlie unit is bjuod i>n that of 
TChrlrch jusl iWcrihed and was nifldi? h} crim- 
liariwi] witU tlie ijcrmal unit obtained from Ehr* 
lleh*s Institute. Franhfort a. M-, Germany, 

AntitoKinp ore purehnacd on tho open tnarkot* 
by ofiicora of tl:c Fublie Health anJ Marian- 
Hospital Service jind tiwted in the Hygienic 
l-alrorntnry for frfdi-rtrj, frci^ilnm fr»>in oontimini- 
tion br bnctcria iitiU dipniLcnl poi^ns, cepecialTj' 
tct^nu* toxin, nnd QooUy to infiur^j o^ain^t OiCfiS* 
of pro*ervfltivei. 

Tb«; method of tUt^rmi nation of potcno/ it tioi- 
ilnr to tliat uncd by Ebrllch and prerlouRtr 

While mice &r« inoculated to tcel for au ciccm 
of preiprvativr, (Trikresol being tlie one mo«t 
employed.) If Ibt muuitc *1iowb trumbltng or otbor 
eymptoms of poisoning afUr iubcutnitcQua injee* 




tion oi 1 cm;, uf Hcriini, uvor 0,A per cfnt^ tnny bo 

Other tonni and bacteria are di*coti;red hy 
iulniprhtonprtl injection of guincA-pig. 

For tFiorapeullc puqioseB, it 1:1 dc^airubie to have 
• t^nim of high value iu oM&r to avoid giving too 
larg^ (jua»lilies. Severfll dlplitherU serums are 
an the iDarhct which have a value of 500 unite to 
the cubic oexitimoti^r. It i? rliflicult to immuniEe 
abOT« tliU poinl. 

In ffuiiiu cAtietf it ta defirfilile to txjnccniTRte the 
antitoxic 0cruni. 

(ri^on hnii ilerised a means for thia dcpcnJiog 
on the fnet that the antilotin is ctoaHr AMociatcd 
with 01 cr7mpii&09 the globulin of th« ««niR). The 
rnMhod ia a« follnwe: 

To from 10 to IS liters (if ptTum, a satnralwl 

Intion of iLimnnnium BulpliAte U hdiJe;! sitailuaU^ 

til prwipitfltion U complMf. This liltratc ie 
then pomovcti by filtNilion thmu^-h paper and 
<Iifl«o]Tc4 In 1? Uterf <*1 water It h t}ken ftrnined 
through ghujx to remo\* the Qll«r paper. 'Hie 
ttolution ia i-eprecipitateU viUi aiDmoEiiiUD sulphate 
ft&d the prceipitotc r:iBoved ^ before. The 
pr«dpitaie u th<n dissolved In ^ lilere of b 
«atiirtt«d eoTntion rif «m1hiin rhlerld and filtered 
thraogh gauve. Tliia K^httlork i^ ;i]lGwed to &tand 
over night Jind ^e supcmfitant fluid rcmored from 
itkjT procipLlate which forms- The prccipitflte i« 
vnuhed with sfliururod ftc>dium ehlorid and the 
wi«hiDg added to the flrfit fiolutioD. 

The eombiued nolutiona iro affiiii] precipitAtod 
with ntnraXt^ flnni^^niiini mlphnte nohuion and 



the [irecipitBt*> coll«4e<l oJi fiUi?r paper and the 
mui^turt prc!lR(^l fmrLially out with filtr-r |mjK!r. 

The precipitate ie then di^hzod in parchment 
paper in riuiiitn^c water for lhn»a dav*^ a sinal} 
amiJiiDt af chloioforni boiog added as a pre- 

0n9-ha1f of onv per cent, widiutn chlorid ia then 
added and the &(]lut]f>n filtered twice tlirougli 
Bcrkcfdd Eltcra. 

In a itmiTflT way t!ie U. S, Government lias 
provided far 4hc rutnhlUliincnt of n legnl totflnii^ 
aatitoain unit and the control ^E ecmm pn."Hiuclion. 

Owing to the fact that, tptamw toxin ii; vpry 
iitjihlc'^ thi- t<T\in ilstlf irt kepi for i.!um|mri»<3ii 
instead of tlic antitoxin oe in diphtheria. 

'Tiie immumiy unit fcr meaeiiriog the strength 
of ti'tnriiw antitoxin thnll be ttn limes the least 
quantity of nntitrtnnii* eenim noi^eisarv to save 
Ihu life of a 350 grflm ginnea-pig for ntnely-six 
hnuTK Hgniiiiit the ol^L-iM] h^l ^aes ci n atdiidard 
toxin furnished bv the Uygicnic laboratory of the 
rublir Hciatth anil Marine-HospUal Service.'" 

TImt Ihi? Unitf^ States govnrnmnnt i» fltlcmpt- 
iog to gUfti'd tJiL' qi^alily of antitoxine on ealo in 
OUT marketfl jn apparent from tlm fotJowlng vtate* 
menl :' 



"Tbr ftct Df OtitiKtr«. nHTiiVftl Jair 1. 1902. fbltHvd 

'An utt to Kfulnle Ihe hIf «f yltvafn. kPnimh, IoiLdb »ad 

analopiUH r'<^'^^'> '" ^1^' Dlatrlri cf CtlnioMn, 1i> nT^l«t* 

1ittcr«lntA Ti^tnniai^o tn •Attl &rtlolf«^ and (or otb^r pUT- 

S, Truni litiHnTiin. Thp ImmnniTf J'nH for tftnoilftrilltliv 
tnpbtbVTiK AdUIuiJd/' DultrLlu .\u, 21 nf Ua L1>jcl>-ulC 
t^bOrttOfT of (be Publlo nctKh ud UiKim llo*;ilijil Si^rvlco 
of Cbs TJnlEcd &NTn» 

i?j:-ii//.vJT/o.v OP Bfsnutig. 


W^it. II, IftOJI, liDiJQVti] ijpvn ibr (SLrKior of Uif- lUfleak 

oralory trcm Unt I0 Ointf an Ibr o^xrn piflrkci ^T afflirvrii 
of (be ivtllc ItcaLrb uriJ MaHoo UotiiltkL Hei-Tlo^ itmlorkf^ 

tKKigTit tram rrlldttli arn^flDLt, who keep the piDdui:i oadtr 
prpipar ffODdlilcEiv aF llf'i^ iroipvrattirt, *(« t^priral gndt* 
of dl^btlidrlA kBiUoiln mkOa lir «'-'ta ltcaa«*d manufic 
tn^fr art b«a|bt ncd hdV t« (Le Ujflftnlc raborat^r^ bj 
ntkll f«r (hv pitj^oni of tb*M tt«tv, 

"Thr Hnimi nr^ t«atad not onlf far |iot«iirj, biit kIk I« 
rii^r«tiii1ik« ita«ir fncdam frcnn c&nfH.nlfiBt!DD br rm**ljco 
tHU-T«rlt. ftn'l an*1lr to Infm Vho nbitmci of ch^aiL'4] [»L 
mrtnt. *«p*rUlly rvtanna imIii Koln li inAja nf Ihn pbft- 

"\ f^Aivriil mrmrirBniliini la maM of tt)« fi^« ftvMi ftf 
fCit msniiriflnr'*\ nn «1il*rl an IhA luri*!, «■ in iri« niiin 
btr Of [)nE» ritnuinM m Iba t>it<'>uif^< ana tM dhrp iH->imri 
KLh-li rtto rnaTrnTH nn nnl ti* n[tiMrr'*fl M^roDiS k rpaaaniibl« 
jlntihr in r1'l<t n viWrllr rraiill. Nolf |> ilm mndF or Ibo 
mit&urnrriirrrii romt»Ilaii<r wlrh thp law r^nuirme iTiaf tbv 
prfilnrf Iw iilBlDir miTkiKl wirn Ch* nam" of ih* nrtli'lJi, 
Odd fne name. lOdmi And l]«nii anmher of inc RiiiQii 

"jMMui^uflntloi tbal nruluLiAriy vomv !■> lUflit Mi Cb»t 
Himliutloiii an ac oacc rt|>orli«d 10 die Sdr^tirn OrntnJ. 
V. fl. rublk Ilaltb and Utrlup-Uotfiltat SprTJcVn "rbo 
UkH lb« mtgwry bIi^i* ri'ijulrliii Itm IminnEIatp irUli- 
dfAVlJ nf (bt jMrtfculit iM of hj'Miii liuiu ttia varLirl auU 
likMlIitt^i mtatcrM (<> prrwpni 4 i*|-finiin <ff rlnitim *■< rora," 


Tbt fi^il tdllEoiL ft (lit ToKi^d aialM rtfl>DiairO|Vka, 
httay tht tlgtitb a*«Eb1iil i*4l«lva, |U<^>. irhTcla la to mp- 
^••r riiorilr. *^f' roDtdlh an afiikri>i1c ■oruoi fur tba HevI 
Ub*^ Tbt tCruoD win be kaonr oOlcIaklr «■ dntf[1lt>LUierk 
••rjn or t^^nitn mltJ^/ihthrHetun, and Ibn unh will t* 
r«,'(i0iiU*d ■• that a^tfrovcHi or •■t^blixFixl b^ lb* ljall«ij 
Hlfttv4 JHihllr If'allh and Ua^JDO UiMi>fla[ ftAtWn. 

'*rb« ortkUJ tMi. wh^rli tiQB bt*ii litn4lj fwrqlthfjl bf 
PrufMPf IFtnlafltfD %n arttamv. nllt Im ai (nLtnvi ' 



■aKunu AWTiiJir[ir!iiiBicv«. 

of A <1Lpta1lK-Hi. lacLrir 11 ibooM U* knpt In utA\9it% glHM 
panTillfl9f4, In ■ Otrli I'ltc'i^, «t F*njMi'iVdP«i bttwHB 4C' 

•flit ir." c (•«' Jitirt i\ii' r.>. 

"A jcllovlpn ar y«l low Lib -brawn. triifljit«nni er 

■ILfbtIr larbM lliniil. fidnrlMn ar hailnir a plifUi odor. 

an* lit (be pl-CfDCO of IbC JUJCLMptlC U*ua M ■ DT*- 


■Sirteioc rraviu , )>oaa tu 1.040 fct aa' c. (tt* fo. 

"AqtIdlphCbcrIc HBrtiEn fiiAdaall; toopi Ub powflr. tL« 
lent Ln one /v»r vflrj^lDf bol^oon 10 p^e ticot. and 30 
p*r fUDT- 1£«^'b L^onlllnar ahtufd b* furuLihed ^vJtb ■ 
UbvJ Of ifatvmpnc, fftvlag fb* atrrnfth of iTin iMt 
dlpMbnrtrk ■^rum, i-iitrmwd i» anTiTmLc lieiiIm tEb 
nurtfi atail iwrrf^UCP b; vninmr nt lb? loriippllo lined 
for lUe iirtsPrvAiii'Q (>f Lhv Un^m lit mipli Im iiiuiil), 
ifav Utiv vbfC] (bp niilMluMbi.>rlc acrum mi liii LtoltiL 
■nil (li* dale D?iviii] w]]Il:1i ll wlU net ba't Hit ulniuclb 
Ifidb^Aftl oa lb« fab^l or utAlsD*"^!, 

"Tb« AUnditfd af »trrai:(b, tiiirqaod lu lulli «f acil 
tokii; powtr. thoiiLd Ijq llinC npi-roTod ar aiUbtlvhrid bf 
tbd Unllffi] Watfv ImUIc HnUli and NArlnu Hf^plivl 

"Av«iiiP> "loio I 3,000 unUt. 

"ItrTinnnlflnf rinv tcr wtli pvtiuinii: aou aniti." 





Because of Ui^ iaiposBibility of obt^ning bao niai*iri« 
teriil toxin» in pore fonn, no conception can be ** '" 
gained of their oompoaitiOD in terou of atoms ot 
muWuIi?!, fllUum^li il rmttl be asemueJ UjhL (liej 
hfivfi •omc imknoMii im^lccwlnr rtTUcture. Inftr- 
wees ift to UieiT nulutc elthI slructure can be 
gaion] obIj by tneaDs of tbv biologic riLpeniiLmt, 
i 0«, their offecta on aDimali and oniiDal celU 
nndor arbilran^ ccDditioQ^, 

Wild) & toiiii and ite aDtitoxIn are mixed Iii 
suitable projiortiona, Ut« mbiture become:* non- 
toxic fts Om TQstilt of ch^micJii nnion of tb* two 
scibetaficefl; each molecule of to;im hua combined 
with ft molecule of aiitit/)xm to fr>rn) a rev non- 
toxic molecule wbich may hr^ q)oV*n of b* the 
toxin-antitoxin mol«iik\ It tms at one timo fluj>- 
posed that Antitoxin had the powor of dctroying 
the toxin, perliap^ by & f^rmenf-tike action. To 
tvo instjuicfrd it hrs been pognble (o nhow thnt 
this i« not tho case. Ordinarily toxinfl sto mora 
suflcvpllble lo bent than aDLlttiiinfl, but in Uie cnse 
of pyocTftncua toxin and ctnnkc renom the anti- 
toxJEiA are th*? mort' sJiKn^piib:^. WssHei'TnanD 
fbtmd that when ft neutra! miitLirr of pyocyanena 
toxlo and its antitoxin was bcntcd to q CGrtnin 
tanperatoro the mixtnre a^afn booame toxic, and 
Cahnalbe- mndr^ a mmiUr ftbu'rvnticin ronremtag 
ven«in and antivenin. ff the toxin had been de- 





ftro^r^d by llie aotitoxiD Ili« lolution cerlftialy 
wrouJd not hjive rcgamuii its originnl toxicity <m 
tho applicAtioD of boat 

Tlie foJlowiQg fact« ad^ aupport to the view 
timt iicutrolictitd<Ka conFnivts of chciDical udjod be- 
tw<>cti tho two eub«taiio«: 

Fint, nculTEiliKntiori lAke« plnci^ A^ordmg tn 
the law of multiple proporlioiu, i. e.^ t«a times ;& 
given cinouitt uf antitoxin ivill ucutrtUisi^ n pro- 
[KiHiotmti? iimoimt of tociii; fi«!cmd, itf-utraJtzittiitn 
is more ropid tX worm than At cold tompcnxtnrce; 
«id, thirri, more rapid in concentrate*} than in di- 
hita solutione* Th«ec are ^me v«lUkiiowD lawti of 
ohemical nactions* 

"Emil Fiftcber has shown thjit in f.he fermpntii, 
tJcfi nitc n lorn -groups f>f special coufi^ration ons 
present which above nil olee me Ti?<|U]Gtt€ for tha 
whole ph^imrjienon (of fermentation). Only »uch 
>i]bhta:iccA ns possces a J^r^^up to which ttic fermont 
^onp coFfc^pondfi, lu lock to ki-y, are subject to 
Uie aetjou of h particular ferment" Tbi« dpplica 
to the ac'tien of a particular ferment on only one 
kiiui of KubitunL'e. 

Uavmt' this conception in mind, Ehrlich ae- 
Kume« tbat union occnrg between torm anrl anti- 
tiiitn thrHiigli n special ^luup of uloniB whidi ttie 
toxin moloculo poBBOflsee, and whidi Hts into^ or 
fomiipondK f[H<[rz lie ally to, aaother group uf atoma 
m the antitoxin molecule. Thc^e ar& spoken of 
fu tho bindinft or biptophormia groupe (hupto- 
pboro*) of the moIocHlcs. Tlie haptophnrmw 
(TTOup of tJiO toxin irtoloctjJo ie highly epecific ynco 
1 toiiu *:aii be ncvitrcibxni *>]i!y by iU ijwti pnti- 
toxin, ond natnrnily tht^ haptophocous croup of 
Ih^ antitotin ynoleeitle must he e*^ually ftpeoific. 



Th6 ioida molecule cr>otaiEu not only a hapto- ismitiiAf-i^ 
pboroiu group, ilirougli which it unili:? with niili- 
tnan in ohq inauiaos ot, io another tD^nncr, with 
tltnic wUk iu thj; production of diao&^e, but also 
ccrUiD coofltituvikU in which tl)c fpcctfli: activity 
of the eubdlonce rcaidc^, aud by wlnL'h it produced 
clian^cs in tinu« colic, on eonibining with th«ni. 
ThU foocttODal or (mthoffeDic activity rvMtlM iti 
this M called tc«ophor>>ii« gn^up of the mdkculc. 
Il^nce th^ Ikflptoptiorovis ami toTophorous gronpH 
ore thv liTii struittiral elnncutji of n toiin which 
mskf hv rcco);»ii?i1 l>y hiolo^it i!x peri men t^. 

It Sa A pefultiki-tty of lovitix th»t tlif^y \ate u cvr- TdvnMn. 
tohk smouDt of tlicir toxicity La tho coar«e of tini«, 
although their binding' |>oweT for tntitoxin romoioa 
pniL<Uc*ily i^TJchnrigivl. tn Uii> Inn^ugu of (lit? 
tomu wbicb were ijacd abovo, the to^iophorouA 
gnupc may 4ogcnoratc' or (liaappujir and k^uve the 
haptophgrixm groupi intacL Toiin^ i^lijch huvc 
ucdor^Dc thifl dioD^ ore caUod toxoids, 

Further evidonoe of the i^tiu^nco of toxoids h^ 
in the fact Ibat whrn nncA for tmmtiTii^Jition thiry 
cause tbo formation of untiloxina^ This is poA^K 
bto only wh**n thi- KiThvlnnct Is nMi* bo nnile witli 
tin ti»ac rell»; thcicforc. Ihc iioD*ti>xic t^)!!!! or 
toxoid has retained ita haptopfaoroua f;n3iipe, 

A toiin ftn1ir*"lr fnw from tr»xnhl* Tin* iicrv«r 
bctfi obA^TT«d, sinoft «7(3i dnnn^ the fow days r^ 
quired for ilt pToparfiUon a ««rtaln amount of 
d#gr-ni?mtion orfurn. 

Additiondl mformnti^ii conceminj; the natvrr 
of toxin hti* bf*en f^.iinis3 hy oxperi minting with 
mijctnr" of toiin and cinlitotin, in whii^h \hft twn 
are prweat in Tarvinir propori-ion?. Thi* w the 
"partinl Ktcnnition" methrvl of FIirlieK Through 

Nv<h»a ar 



Til* 'l*mln 


a vut nnmbpt of experJmaiDts Ehriidi obtained in- 
formation vfhich [termttted Itiin Ut csiLuitati; timt 
21>CP "bitiditm unite' no; rcprcwcntc*! in thnt 
amotmt of diphtheria tfixiri (hypathetlonlly piiri-) 
whicli t« exactly ocutraliietl by one ivntitoxin unit 
If the eotire amount of antitOKia, i. e-t 20Q/2QO, 
jfl a^dod to i^ic qimDUt;v of Loriii in qiiedUoD, (.-oni- 
piotc ncu(rAli;^At]ou of ihc latter, of courne* occura. 
In case the totin ie entirely pore, lt»9/S0O of tho 
jiiLLE4o:(iii unit vtoM ileslroy all but 1/SOO of the 
uiitiol toxicity; wid 160/SOO, or lOO/SW, or 
75/^*^*^^ ^^j <*' tb^ aatitoiin when a^<led wontd 
permit corresponditig ik^c-efl of toxicity to be 
ddnonatratcd tbrougfi aniiual inoculat^ocui. It 
wa« fon^fi^ liowever, that neutralization di^ not 
take place eceordinj: to this nimpte acale. The re- 
nilti were eompUoaled, and Ehrlich has found it 
cotiVWiii^t to <!j[prrM» thrm xraphii'jilly in tin? form 
of a '^tojtin apectrum" {Fi^, I, S, 3 and i). For 
exftinple, let l^y/300 of tlie antltojin unit be 
aJfJed to Ujc proper amount of the toxin. 158/200 
to another similar amount, 197/300 to another, 
ftti*.. (\n\vn tn 150,^00, Tn Iho Inst miitnre, T,Q 
out of the 20D binding units which the toxin ptwu 
wee&a are froo, and ti^oee 50, rather than aoino 
nthrr SO, are trcr? hwuiiw^ they have leiss [ifliiiity 
for the ^ntito^in than tin? ioO units whi?h vcr*". 
boimd. 11 line been f<M)nd that those unifa which 
first bLtome fica hnve a low ^legree of toxicity. It 
wna thoncht that they might have lo&t thrir t^io- 
phorous pioupa^ i. o., that they were toxcidH; and 
because of their "vre-nk o!Timty fw antitoxin ihfty 
WGfo colled rpitoxoids. II was found, however, that 
they poMMsed « rather eonwtanl tlmuj^li low degree 
of tojcicit^r and thnt the toxic action v»% charactoiiS' 


tic Injection van followed by eoiiie loca! edema, To^^m. 
then by a long incobatjon period, and Aoally b> 
<adicxm And f:anJ)iu«. On itcLMSunt of lliit cluir- 
iitlerfalitT (oxio «cliori :uh1 ilia limy mcrubjtliuil 
period, EliHich hna concluJed tliat the ao-caJlod 
CT)itoioid ia in reality a socond toxin which ia so- 
.cTOted by the diphtheria bacillus. This he nivw 
flt^M^njitij>i n4 toion in orilcr to Oi^fingiiihh it from 
that ether conMitucnt of dipbthcna bouillcn, the 
toxin, vhic-Jj cnujca the acute phenomena of dip)i< 

A ifTvot dvnl of ditcatiian «tiiOii^ inrcttigoit^n. The 
finfilJHii cbvinial. Airh«utuH. ]>■* jwii'nlly Hll4^iiii>ltiii lo 
A]iply c«rlJi!n prlnriplHi uf pbjairiil rhrtmlhlrj (a t1i« 
atady ti lonini ^n^I unlils^itiM' It ii n v^'Hl known (uot 
Alt vouiv fhemJoi] ^uUlu^iLiXit, whvii iu Mtltjiiun, limv 
u> pmtcr ur l>rMkiTt^ up Intn llitflr <<ori>iilU]«'i]t ["irl«; 
tliiii ftoJiviii i^hlorld br«iik> up In pArt into nodtiim uiid 
chlorin, B.1 fodhim or chlorin icdh or elrctro!!^ (c*- Tli« 
illuocliteil MJcUum or cMorln mny tlicTi enter Into com' 
binfttKjn with miy otlior luiuitla igb»lAnon wbich niiiy 
bt pTfuvnt. AnhtitLua boldji lUat IbU li tlic cue wLUi 
UiiT lull n-nntJloji 111 niuliriiK Itmt il fiiuy tu a t^Hltln 
n\m\ Benin br«Ak up into t^iinto lo^in km! anlitcain. 
Uo Wli^rrfl timt thin (lU*(>ciat«l toxin U U'c MiLmtaDca 
irtijch Eiirlkli liu b«o irallm;; toiun. Mailwii. »ho 
formrfly had don* mtich nnrk irilh Icoxitw, ha* now 
JoEueil uhh drilivr-iiid \a au|j|3art of the <JlH0«Ut4cD 
iJieory. Ikrnlui hi-lh-iift that l-ixoii ftiul Lhe iurl«u« 

ikcpanU fiiluitiinon, arv (ti« r(r>ult of comliiiiatioaa o( 
%iftr;ini! pru^vhiuija of Ituirj <um1 untitoiiu. Hi^ prv- 
ihir^l rvimiianhtv iilif^rinnii'nii hy niiifur'iM Ml f^inp]i>in'-r>t 
oik] antifODipUm^nl tn iMryin); pntpottiank Bnil niiUng 
Ibe d^grtf of LvfJiolj^U prodtirr-t on >i'ii>irtfi^l r^arpuft- 
cln. In *pll« of the r«iiwnabl<-n««a vf thU ihuory, Ehf' 


lypxvTwy ASD iuuvxiTY. 



lidl Hb4 hl» Collowi^ri couUnuc to uj^lioM l!ic toxon o* 
OB IlldtpMldsnt Itixltr htiljMtAiii:!^, Bud bavv piibhuhcd 
iddttloml eip0rlnipnr« Id lupparr llioir potition. 

lA-t om* tioiv lEiM rit.ill Kmalkr umuunbi [>f Lhe 
nntitoxin unit to tJio SOJ binding unite of the 
toxin. When HO/VtfO axe added it ie found thai 
[L iJirriAin iimtmnt of true toxin remains fn.*r, tJie 
quantity which ia unbouDd being in direct propor- 
tion 1o th« iiiiiouikt of anti(o!iui withheld, CoitBf^ 
qucnlly when but 50/200 Hntito%iii unit i« added 
Uio amouDt of free toxin corroaponds to 100 bind- 
ing units. If* toxin only remiiinL'd it coTild 
tbcQ bo Aaid tliat the coriAtltutioD of this toxin h%i 
toxin 150 And to-\on 50. However, it tna.v t>0 
f<>uncl IJuit ;l* 4^/Zm. 4A/fi00, rti*-, t-o 0/300 unti- 
toxin unit arc addedi no increase of free toxin ta 
found, ullhoiiftli tho antitoxin nddod ha« been 
bound- In tFiin raf^e, thi^ SO tiinding unite of toxin 
which havo the i^rc'ututtt nflinity for antitoiio tira 
uon^toxjc; i. ^^, thoy nn» toxoids, and %\tic^ tJioy 
have the maxtmuin ufTmiLy for antiloitin Uicy arc 
called pn>tf>xoide. 

It hRD he^n assumed also that a toxoid mty 
«iflt which has an niTimty for inlitoiin exactly 
equaling: that whit^h losin paEec^etK; tliiB* as yet 
purely hypothef.icnl poriEtitiii-nt^ hnare tht' mintr- of 
aro toxoid, 

ripir^ 1 In a ;7ruphtc ropreMntntion of the 
toxin j«at diTsrnbrd {Maflw»M). PmbabTy no two 
toxlna have tho same eonatitution. The toson 
wnfv frir exnmple, could well ho mwAx Urffer in 
ooe dipblheria toxin than in another, 

Kefincnients in erpori mentation *ho^v that ovon 
tho truu toiin is rot uniform in ita vimlpnce nnd 
ita affinity for antitoxin. Accordingly a proto- 

TOXiy Si't^^THJt. 


• ■j>ii 

P'f'rfttfa;/ ^Jllrtir'rtiTVif-trtt*'^^ 



rr*/ir**i*rf. tf 



rifiiK 4. 
KitfUK* 1. «, C «nA 4 Aft taken from AKholTt "Ebr- 

rau 1. iDo:^. I'lcor* 1 U « lotln ■pefitura iiarki<l out t*j 



toda^ ft d^utorotoxin and a trltotcilii may be iw- 
Qgniied by tliit mtnn jiAriinl KaLurntioit mctiicKl. 
(S» Ill^i 8-) For cxampb. it may bo found tliat 
»h«Q a portion of th*> onfilotin unit between Ihe 
limit* of H9/S0O nnd l$5/300, is withheld, a 
tDxin ifi l^ft tree whidi U Ices virulent than that r«- 
raainiug free betveen the ItmiU of 124/2G0 iiu\l 
100/200; and fromthU point on th« new nnbouncS 
toxin miy be stilt more virulant The Hr-at would 
be tnLoto:ciii. Uin twcnml clcuberatoKifi and the 
third prototoxio. 

The "spectrum" o£ a toiin chan^ with iti «g^. 
Tho prototoJiin, aod portions of tbe dcutcro- or 
tritotoxtn may di»ppoar bccftnse of toxoid fonnA- 
tfon. Such changes have l«d to tb^ recognitloin of 
aa alpha luid a beta niodilic«tion of the toxin. 
Tfa<^ aJpba modificfltioiu of all thre^ toxins readily 
beootne toxoids. Ontj the Ma modfl^r^itfon of tha 
dcvtCTOloxin Temnina consUnt The toxon also 
nvnaiitt T^latiwly intact (Figs. 2, 3 tDd 4). 

This refy cvmplkated melliod of iDT«ptlgalIoii 
VW tlM nndertoktt br Madfcn in the studr of 
tvtantie toxin, for which a soowvlist diitilar 
**apcctrtuii*' was constract^. 

Siidi vp««tTa ba^o not been wioric«d out in d^ 
tti) far aonM of tbe rfgottbV loxinE, sa nrin and 
iMd. b«t it is kMwa that tbej form toxoids. 

Some «if the toxiiu of UMke t»wixi difTct from 
tb« bacterial toxins in atnidu rg (pa^rni 4?^1-4S1^. 

Tlw idea WW oril^aallv ad*t»0fd tbat antitoxin 
it tTUsdtomed lox^ t ehange In Ibe MIrr bar* 
ukg b«M dMed &roq^ aem mXkm id tht 
liiiim t&tlMte«M»tb»ajBMatof uibtoxispv^ 
4«oi4^ltaBU be TVt^}f «q«halnt to tlbe anftont 
of loaEiB ioJDCtel 1%^ boverrr, wv faa^ aot 



to be tlie caee. A wngle iojcL-Uuii cf tauuua tnjciu 
DDAy pdd 100,000 time* tli« Amount af nntitotin 
tiec*w7 to a#Qtrfllis« tho toxin injoctod, An in-* 
bcmtiDg cipcnriKst ia oa record wLJcli Hhows Uid 
^Uaoy of Uie Ti«w Juat mentioned. An animal, 
the leruiii of wlii^b nun riLrh in mititdiinK, was 
bled rcpcitcdijr untU fui fimoart of blood which 
♦qofllM the total quaniity norrualK pree^oi m the 
uiimil's body wiu dniwn. Yet the Antitoxic 
pmrcr of Uic new fonnod blood va« prActfcalty uii- 

MctchnikolFf tfl explain Ihi* '*OTrrprotlin:ti'>n" 
of antitom, baa ^v^GfAcd that the toiin moloculcs 
uuj be taken up by plufrocytie evilh nud hrcikt^ri up 
into an indctinitc nacober of «maUcr molccnlr^ 
Mch oi which then is altered in eome oh^ourc man- 
ner M Ji3t t{> fnii-»tilulr n inr)li*fnt!(T of anlttoxiii. 

Tbc »icwB of Khrlicb hoTc found wide accfrpt- 
anc^ and li&re providM a valuable voridng hy- 
pothcfifi for mnny isTcrtigationi. A con^deru- 
tioa of lliie subject introdncos orte at once to the 
well-known side-el^aln Ih^ry of iromniiity of 
EbHi^h. ft inaT be conniderff! briefly at thta point, 
id «o far aa it involvoc tbo origin and nature of 
antitoxin. Khrlidi oon^irlen it fuD^lainentAV Jn 
rOfE^rd to the mcbibclic activity of celif^ to oftannte 
that the cell cotutitoonts must ont^ into ohemtcal 
eoinbiDntion with ffMJil saibatwJit^ui in imJer thiiL Oie 
Utter may be made nvailnhle fbr thn um of the 
oelf It is suppoted that cells contnin cot* 
tain alom groups of unknot™ cheuncal nature 
which moke po«aibIe the binding of food vuh- 
ttan<vi, TJie tmmr. nT n^ci*]t\jjr wii* glvt^i to mch 
groups, since «ubstfLncce arc roccircil into tJic cdl 
throng thena, Tnaunudi aa the foods and tome 




fyrscTioy and rnxuKivY. 

M»iMriiei<y other ftubiLtJU)ccs which pcrctrate the cell* differ 
""** *'"■ in their chemicd nature, it is probable that lh«ro 

Arc various rrcuptur; tnr Ihr vnrioujr 1}'|h9 of eiib- 
ftfisccf* The binding, however, is but & prelimi- 
nary itep to profound changes wliioh the «uhvtiuu:i> 
Rifty nftxt «iiflergo> throiigb the actioTi "f othr-rH 
more vitaJ. cell conetitupnle. That is to say, Iho 
reoefitnr is huf a link to bring the stjb^tanf''" into 
TcUtioiuhip with the viUl octtTitiefi of the cell, 
which Ehrlich BUpp<w« may rceijo m a hypotheti- 
ml "KrisluntjKkrrn" (m-linn <M*nti"r or TindenfiV 
In view of this oooccption one readily understands 
the propriety of conttideriuj; tho ri?eeptor as a side- 
ddn nf lb* "f-ffUfufip^irTTi," just iw thiT diemiat 
ftpCflks of the raricuB jm^oiip^ which may bo at- 
bithisl io the bt-nwil ring, or benzol nadt-os, Mt 
»itlechniiiEi (Svr L'hupler MX}. 

In preceding pagofl it hae b«en emphasized that 
n toxin, ill urd(-r that it may injure n, must 
enter into chcmicnl comb in ji lion \nth its cooBtitu- 
enU. and it m a fundaizienUl teiiot of the EtiHicIt 
tliwry timt tliiit union it one wlnph UUce^ pUf-'O 
hrtween tlw U^x'm nnd a c^l! receptor (side-ohiiin). 
The cell ret:cpLor, then, either ifr a haptophore or 
posGestee a haptophorc a* a part c( tts Of>mpl^. 

Afi ihp phvflifilngir- flrmwnds nro prohably m- 
eponaible for the character of tic vaj^iou* recep- 
tors, it U not likely that tpei^iiil n-ei^pt^ni ai-e 
crcftti^ whim %innc itnLiHunl niibsljincc. Kr a hiic- 
teriaj toidn, \& introduced into tho body. Codao- 
quently. when tcxin unites with a c<?ll. it probably 
occupicA receptor* which, under nonnst drcum- 
stancoc, an employed in aom^ physiologic proceed 

If aome Inert, non-toiic eubstjuiee ihoidd e<irn* 
bine eictcnf»ive]y with ceUa, n corrf^iponding niiin- 



bcr of roc«ptor& which ordicanlv tut oMd for 
Donnfi] m9t«V>Ufini, would bo tbrovo out of futM>* 
tion. TToion of thi& nature irould be equiral^nt 
to «a injury of the cell, and it is possible thai the 
oHton of toxoids is ol this miW Tinturc. 

Ocdvf mjid of latin ujiLtlut; trtlh thu ivEl rL>c«ulrar. a. OU 

™i»: 4. T<n"('hor* of l^rtHi mnlnpnl* ; f. htplophor* of tb« 
evil rr?f»tor^ Ttoia KiuMch'w '^bluwiMU'«ctiiuiiKi?Ei.'' 

>V*tbBM*l'« &!f*t^tll uf M^iIIlIiig. tsL Tilt. Tbl* cut 1* ll<7t 

to }/t ukvii M rt^ffOPtttiDg: tb* Bcruir norpboLi>cT or toriai 
» cMI rvfvrran, Maiuioi l« fcn'iwn at tbdr nioTDJiaionr. 
If. Iiid«*d» tb<r bat* Apjr. The cuf I* IoIchiIfiI tnarfl/ l« 

When toxin iinitM vitJi cclb there la involved 
mrt oulj th« divvnion of coll rocsptora from Uioir 
mttoinary fiiDi^UoiiH. but iii addiUon the ileatme' 
tivc actioti of the tocD on the vital piirt« of the ccH 




«i«* m§ 

00 fh« "£«vl«ifii!vm"). 1^ mm 
laaa istrvdnced, Uw gmlv th» Bambv of otQ 
jwjqptuu boQOid^ ind tb« grcrter tbt inj-arr to U>e 

Is OM A BOD'otu UllOBU 01 toXIS MO 

h&mdt hmt soCdcDt to cans* ooot iaj«r7i 
do« tilt «cn nopond to tbe injiirj? W«%er^ o 
frv it^m 1^0^ gsv^ upmWMt U o bjrpodMS* 
wlbclt ti bold lo bOTO lene b«tn&£ od tbu qoet- 
tioiw la olndpiv f igMoratioo foUowii^ ^v? 
1M eewMoa that tiosos har« tb» taid0DC7 to 
w yo duc t Dot odIt to tte i rtto t of awUiie good 
Ibo iaJvT, bnt Ihot u ii« i» ol bow ttane to- 
«nha. Th» cWrei^ nimpfo of this omimwca is 
tLst of Kor fonDitioa, ia whidb a o wwiuds <nc« 
of ttov oooDoetifO tivoB c«lb io fonaed, 
w^idi btn- diMpiMui in port SiMilnlx, vImb 
o ooo^fatal oinottDt of toxm vutos viSi fto 
reor^iton. m odl 4«f«ei Or injtuy a crootod. no 
mO bos for pnotud pGrpoas ktt fo mnj itcefH 
tort. ItiiA lOM oAarts the viul octnitm of tbo 
«A aio *i:Aiwjtton" and m« ne^torv, idm^ 
tkol «^ thooe oocitp<«d, one reprodoerd Follow^ 
IB; tbfi liv stated, tfaer are reprodiiic<d in czoc» 
of ^0 nnmbor tnjttrcd. auid tba «nov aaj bo to 
fn»t t]Mt tho c«ll m«y 1h* omfllM witit ttoih^ 
» oreHQM that maoy are diacboTYod and nach 
Ao g afti f ml cinn]ati««. Hkm coet-olf itc«ffte^ 
or «>d«-cli^va« itill rvcatning thoir povvr of mi^ 
itts vtth torn. <nB«litnto oar antitoxin*. An 
Bekruv hw flatad it* th« receptor, vbca attached 
to te celt* it xh^ Ajrnnt thrcti^ v^kli Iho lotler 
is oltnckrd. but whrn roM oft frnm the c«>11 bdonmaa 
ilapiotorttir (Pi(. «). 

ANTITOXiyS. 203 

Ad r^ards tJie strncture of the antitoiin (cast- Receptor* of 
off receptor), it is necessary to assume only the order." 
presence of the proper haptophoroAis group- Ehr- 
lich designates all receptors of this simple type as 
"receptors of the first order," In following 
sections we will hare to do with receptors of the 
second and third orders. 

Waseermann gives the foUowJng list of anti- 


Diphtheria antitoxin. 

Tetanus antitoxin. 

Botulism antitoxin. ^ 

Pyocyaneus antitoxin. 

Symptomatic enthrax antitoxin. 

Antileucocidin, an antitoxin, for the leucocytic 

poison of the staphylococcus. 
Antitoxins for the blood dissolving toxins of a 

number of bacteria, 


Antivenin for snake poison. 
Antitoxin for scorpion poison. 
Antitoxin for spider poison. 
Antitoxins for certain poisons of fish, eel aoniniH 
salamander, turtle, and for wasp poison. 


Antiricin. for a red blood corpuscJe poison of 

the castor oil bean. 
Antiabrin, for a similar poison of the jequirity 

Antirobin, for robin, a locust tree poison. 
Anticrotin, for crotin, a toxin from the bean of 

Crofon iiglium, the croton oil bean. 


tsfKcriox AXD iii}fvytn\ 

H«y fovtr anHtoxiriv for the toicin ol pi^kn^ 
vrhivh caujw* ]iuv fevor. 





Anl.ii]Tt'»Hr'', fnr iti^i^p^ ji iir^n splitting fifnnnnt, 




Aiilift^ruK-iLtTi for (he fenuentfl of bacterial 

The above are true antitoxins. Ther^ erp fithpr 
flubstoiLcefl, however, which occnaioQBllj exert uri 
ant^onUtic action on toxLn«, althocgh th^^.V prnl)- 
iilfly Bre not triH? nntitf>XTn8. For ^-xniniile, it h&a 
been foooil tlial dioleaterin aoutraliice the actioti 
of tetjiDolysin^ the hemolytic toxin of tlie tetanus 
bacillus (Nognchi), and jilao the btraolytic action 
pf cobra venom and cpbrn-letithid. (Sec Chap. 
XVI), On the other liand, it dooa not affect two 
otitcr hemolylic toxini^, BtflphjtolyBin, wliieh Is 
derived from tlie ataph^vlococcriia, and arachvoly«in 
V'liieh li obtfjincd froni spiders (Kyi^), the aotion 
of choln=t"»rm, th<?ref<»ro, is in nn set^fle specific and 
apparentlj is of a difTerent type from that of 
unim nntitoxinE. ThU is furtbor mdirflio^ by 
tho raE:-t that diloe^lerin also inhibits the hemolytic 
activity of <ertuin stib^tnnce,* which cnn not be 
olaased wilb the toxins, 9. y. flaponin^ agtridn 
(Nii^uelii), Fluiils i^hidi cojilnin rliolesterin naU 
uTDlly^ ns milk, Krum and bik» have a aimilar 
inhibiting power. 



The discover)' of Hektocn that ccrtnin salts are 
sbic to neutralize the toxic action of eome serums, 
by combining ^th the so-called complement, may 
also be mentioned in this connection. 




A^luliDotion, m tlie bacteriologic eeoae, referj 
to the dumping Jiud Ectliment^tjoii of a homogeae- 
oua snspeiwida oF nilcro-orgocisnu by tbo action of 

Altliougli a number of investigatorfl had ob- 
E^^rved the phcnonicuon of agglutinatioD^ Urciber 
&n(! Dvirhnm flrstsaw its significance. The^ fouoi 
that the rOtt':tioD was a specific ^ac, i. q„ that the 
wrum which u-oukl cause the fltroQgcet aggliitino- 
tioa of a micro-organism wo^ tliat nf an animal 
which had hcea. made imiuuBc to H by repeated 

Widar# senice conaiitet.1 in the utilJKfltioti of the 
phenoirODOn as au aid in the diagnoeia of typhoiti 
fcYtr. lie is the urigindtor of climfal serum 
(iingnosis. It ii [Wrbape largely a matter of acci- 
dent tlint we spejik of ihe Widnl respfjon rather 
than the Gracbttum rcn^tion, nriinbaom yrns cnr- 
rying on the snme work at the same time, but 
\iVidJil preceded bim in the publication of hU more 
extensive work. 

Tn ihe chapter on natural immnnlty tt was 
&taM tliat nomial eorums oft^ are al^'^ to ag- 
glut.innw haderia. Normal human serxim may ag- 
f^hitinntc Uie typhoid, colon, pyocyancus. un^ dy&- 
rtitcry badlU, an"! occaaionally the stnphylococcns 
auf\ L-lioWa vibrio; it docs not agglnt.jnatc the 
streptococcus anil *omo other organieme. In cer- 
tain Posi*» it miy iigglutinote the typlioirl baeillua 

fititCXB AOOLVTtViys. 


eren wicn the venun U diluted to cue in thirty, ft 
point of prflcticfti impartnnca m tho clinical um of 
HiA teeL Vthfn a normal s^rum U found to hiLvu a 
bj^ dgglutinating power, & proviona infection br 
the mIcro-<irg!iii[Hm iit to ha OiOTif^lit of. Tltia poa- 
sibiiitj receives empliuis from the fjict that the 
•omm of ■ now-born cliild is devoid of many of the 
•^glut;iii]D* which are found in Intrr life, TTrtiirc, 
of the so-called norma] a^^tS^ntiniQa, maQ^r 'iftor 
all. may he ftrrqiiin^d pro^rtiea. 

The term immune ngglntinin in applied to the 
affglntiiiating nbetanet; in a serum, when iht 
pmpt'riy Iiiih dnvf'lfijw] as a result of infecbioTi. or 
of syBt^matic imiiiu[Lizfit[i>ii with the organiam. 
Ttioj' ore formed doriag infeelione with the crgftu- 
JHins of typlioid, Hirdeni, dyj^i^nl^ry, plague, et^. 

For the Artilicid production of aggluttnina, the 
bict^rin may ho injoclfld into the mn*, Biibentane- 
OQS tittue, or in^iilrjufiil L'jivitj ; in ?toiitt* i:a»vit ihay 
may be fed to iLuimaht, rufc^bcd into the akin, or 
aprKTed into tho hmgs. If cfrrtAin micro-orgftn- 
iema arv AealeJ up in a colludiou urn aiid p]uc«d in 
the abdominal envitv of an cnimnf, nn n^lutinnt' 
\i\g B^n;m will be formed; tlio npcewary snbstaneea 
dilftuifi throujili thit aac and vQudi tlinee Ixxly cella 
which produce the a£:^lutiniD, It is not n'>ce^ary 
tbat Jiving bacteria be i»Jeete<l ; in fact, tbe stron[T, 
ot agglutinin ii aaid to be formed by the injection 
of baeteria whioh hOTe been killed by a tempera- 
ttirc of 62 C. Tn ccrtfiin inaUncos a^tEiltnlna are 
produced hy immunization witfi disinlegralioG 
products of baeterla or with bocLerinl extracts, 

Tfwirly all ImrfFriji, pvnn wh^n non-pnthOKenic, 
will gire rise to aggtutinatini; aemms when in- 
jected ; hvt not all hate the powor oqtiaUyH NicolU 

I ID mn ■ «> 


nrMCtioy jso immsrtm. 

Or dOvv » • nnk of in&dboa «r It 

tin. TW «Md «mp c« 

»Udi, d«ri^ iftCectiM or t-iiA«inrr, lo wrf 

«ntt Ifae fiiiMiiiiiM flf ij*"*^— , b«l Mf bt 

toad to 4* ^ >y ly^mrff fly iiiieelli« tlicH 

Mo ^^A. la te AM gmp «n nchW 

nnfy laiiM tk* fbraatson of Mv^stinating 
«f«M: tbr PfMOtete ^maSkm. Thoo £Mti 
Mf W ttkn o« o Iftta of tl* 4kiH* te vkM 
m Bojr cipeci to oIiUb tlir ■jjjnffoiHon rmtkw 
W &■ Mm of tte piAlMt 

TW J<i g wi nt igigltitiflotiiu; povir vUdi anj 
W iMaiDed bn- iBsnnuiaftMD iirki gnttiT. Tu 
ds VtU> ipcib of « 9pUd Mnoft vtech ia m 
of OBO a mm mSsB^m «ba «B^tttic«tmff, 
tad ft cMm aom vUdi n* cf * 
tetivv ID o dilalkH of OM ia tm loiniMi 

tvo fiflmBt Knaaa of tib* 

Ib tMr lUtty to <««m tbc tenatm 
ofiK^vtlolM Ub^nor^MidtetotTpftMid 




tgglutictable Atrain gii^^s a stronp: Agglutinin. Thr 
Lo^ic of Ihw will bociTnir nppurcnt wlivu v« cuit- 
aider the oature of tbe UctcnaJ ^ubsUncc which 
caamt tbe body to produce igglutiniQ. 

Th^t Lbe t^LutinBtiti^ power of the Knim of a 
typhoid pttieftt vari«e from dflj to day tn a fftct 
of practl»l imporUuiOLv It may tie thirty tim«» ad 
Mrong one day aa tbe next, &nd may CTcn di«af>- 
petr entirely for a dty or two, Henoe tl]« impor- 
ttncf of tnaVrng mori* lh»n tuip fi'st in n nusjiidoun 
cue, when the first trial haa been ^o"blfni or 
D^otiTO. There ia m> adequate explniiation for 
thia great Tariatiort. T1 is »tid that mi;lL^l infi'C- 
bona, intcfftinal hemorrhage, or a Buddca poiihn;; 
out of Q^oid bacilli into tho circuktiop may 
cauw & reduction lu the agglutiuatiog power Tliia 
occurrence hoa on important bearing on the poeii- 
bflity of v&ng the a^Inttnating jwiwer of thr* 
teram aa a prxignoHtic aign. Although it has ofitu 
bfcn not^ that jn ffltnl infwtian* n^'gluticine may 
be alMent from tJie aenim. the variations jnst m?n- 
tionod indirjibc that profpions couhS not he ba^ 
Mf«ly OD th^ TtujxH of a einj^o ej^hitinntton tect. 

Tbe agpltilicatrng fiiihstance l^ found in the 
highot concentration in the hlooci 5crum, hut it 
may he dtrmon^trated in the various body Hutda 
and in eitnurtA uf the «ir^*aii-4: it la mucI in \k jmr- 
ti<:ii[arh- rirh in the milk. It is present in the 
•emm of an artlficiaJly protSuf^ed blister, and it haa 
boni rreoiniTirnilpd that hliatrring btr rriujrtod to 
in order (o obtain »emm for the teaU Tbe bile 
<iflcii agjtlntinatesi the typhoid badlhu, but the 
power haa no necevaary rvlatioiiahip to a pre-eiist- 
in^ infoeUoD : it la poodble that *he o^lutination 
in Ihi* ea»n i« dii« to ohariire ^emi^nT caniBpn 


1«a In fl«arp 


JAf£'Cr/y-V SXD ivaivsjty. 


■ IniBlApBiice 
ol ,tnlD<l- 

Fftthor Uiao to tlie ueual B^nmi agglutinin, Becbt 
and Greer finrl Ihnt agglntiuiiiF *>cciir in tlie var- 
ious ho^y fluidi in the folb^irtg ftrd<^r of concen- 
tration: blooil flcrun], th'^rooie Ivniph, neck lympJi, 
trftces in the pericardi&l flaid. least and not con- 
stantly in tlic reTpliTORpinnl finid and bi]tipi^uii 
humor The iidminintrntioa of pilocjtrpin raiisw 
a riae in the ogglulinBting p&V4>r of the toar«, 
sjiutiim anrl soran otVer boSy fluid*; thp tlrng 
incrcftics cell secretion*. 

When typhoid fever ocQiirs during ppcg-nancy, 
agglutinins niay appear in the aenira of the feltu. 
On the oDe }mnil it Iins ht^ji held that aggTnLinin 
pusses from the mother to the fetus, or, on tlie 
other hand, that tlio presence of agglutinina arisoa 
from infpcUan of the fetiw iiself. 

Aithough the milk may be yery rich In agglu- 
tinin, it ii douLCful if the serum of a brt^nst-fod 
child undergoes mndi increase in its agghitinating 
power becauee of t.he ingeetion of tlie milk. The 
intestinal juicce (tiypaiu) digeet a^lutiniiu. 

The origin of agglutinins in the Hnimnl hody ji, 
afcnnlizig to mry couviuctug cAptrinienN nf 
Jlektocn nnd Curiion, the lissue telle of tlic bodv. 

One of the ruoal inl«rosting and important phe- 
nomena in th(! Ktudy of immunity is the so-cnlkil 
rJtiiTtr phcnoiiicrion, Ad animal which lias bttu 
rontlorcd iTnmuce to cholera by repeated Jnjeuliona 
of cholera viLiios liaa the power of digeetlng or dis- 
aolving the latter when they arc placed in the fr^h 
serum or in the ptTJtouoal cavity of Ih*; immuni^Q'3 
imimaL Grubor and Durhem were stuflying this 
phtmontfliioii in the t<^t tube whtm ihny fitsl ob- 
tgrrod the Agglutination reaction. It wqs found 



that ihe flgglotinating property^ as well as tlie bac- 
LeriddliJ povrctr, wilk Jic ruuit of immuni^.nlign. 
iBAcnmch ofi fin mcroaso in Uk bactoricidal poorer 
of a fterum poiuU to ibe eriuleuce of an licquia-d 
inumuutyf the quceti'>[i nattually anie&; Does th« 
SMOOUted property of agglutination have a similar 

Hn7 ob6«rraiioiu indicftU th£kt the \vo acttri< 
ti«s are diatlnci. tliat they d^^end i:>ti ditT^Tect 
nihshnrpK in Oi^ sprum. The foUfiwing are thi' 
important polnta involved; 

1, TJie bflrtericidal power ib destroyed at 56 C^ 
while agglutinins rt'gijt » tflmperalnre of 62 C. 

S. In ccrtjiia ca&u^ it haa imvn j^osjiblc lo couee 
the bictam to absorb tlie u^^^htltnin from th^ 
acrum. leaving the bactericidal substance intact 

3, A scrum may l>0 bacti!ricida3, but not agglu- 

4, During the course of natural or eiperitnental 
typhnid foTcr or ohdlura tbo development of tlici 
aggliitmntiTig anil hnctprEridHl pmrniN mny nnl hv 
pamlld. In dioZ^i-a. ihe agglntinatiiij- pow<r mav 
diMppcfir soon, but the baeterkSdut powvr rrmfltne 
for a loD^ time. 

5, MicrOH>r2;:nniBms which have leen killod by a 
t)flct«n«ida1 «orum may lose thoir toxicity; og- 
glu^nated hacteiia remain viiuleuf. 

Botrodka found an a|]pHfeiit rolationihip be- 
tvavn ngglnttnati^n itrd immTrntly; if typhniJ 
bacilli urere agglutinated before they were injected 
into the abdomen of a guiaea-pig the animal would 
rennrer^ hut rf thry witrft not n^r^luiiiiaii-d dtiith 
rcenltod, Tlic explanatioiL offered for thin hrfl of 
nmlenee is that tlie baoUli b«iii; agglutinated and 
imrnohilized arp m^rp iniflUy taken up by the 



■■■■Ivfi 'I'ral. 

Tbr llitDivrlHl 

phagoejrt«8: if phtjfooytoaiB U iohibiti^ by ft(>n« 

elill viriilont. 

tCijch h!\9 ftttpmptod tfi uso the agglutitiatioo 
test vriih IIj*.' lubi'rele Willus fl* an iud^ ot iin- 
rriunity jigiin^at ttibrroiiWiii- Tliift if; not occcptcd 
fLE G reliable test for th« immunity, bat h pcrhape 
1 general iikilei of t)i<; ability of thr inclivithiAl ia 
form Antibo<)ie» for this org&ijifim. Thia metliod 
was dev]fii?ij inosmueli as the bact<*rJ<:iJal action of 
& serum on the tubercle bacilluf U iiol iciacUly do- 

One miiy use two mstho^U cf (ktennining the 

^k^if!kjtirijilui]> iif im^-Iri i:i I. llir iiiJirtvi-iMpic or 

naked tye observation of the clumping and aedl- 
mentntion of p. homo^n^onn mtflpeTisioD of tho 
bai'tem iir test-tube«; ?, (hf miproft<!0|jk" ob^wrva- 
tion of tho clamping of the orsraniam.-* ivhcn the 
Utter ari? mix^ with EoritEn and mounted &B a 
"lianj^inK-drojj" pre|inniUon,' 

Wlien the organism to be tcstrd grows rjipidly, 
it is the cu^m to uae a youn;; ciilttire, odc which 
baa grown on nii agar eifrfafe or in bouillon for 
from eighteen to twenty-four hmir^ OlHor cul- 
turea of the ty])hoid baoillue or of the eholera 
vibrio MH' jigphitiriHteil wi(h rtinn- ilifTu*ijlty ihnn a 
yoLirg culture. If an agar culture la uacd, tho 
bacteria may be waalied from the surface by pour- 


i. tor a tii>Bf1iit-a»p prvpfimilDn II 1* n^i^vmiirr to ban 
ft iilfilA RiT(1i 1 ftiriir^r-snitrvpd fiptir^ttiAn nn nnf* fttirffti*^. A 
tma at in* lA^miiLn ia hp ¥t%min9f\ li inount*<T nn « «nr 
aThh, tnH (tic Ifltipr li Ihi-o monutod. ari>[} iIOp d4Vn, owr 
I1l# ilf'rirrin[ij[] ^m1 Hi* ■'clui'ii nf ihc cnvfralJiHi ftralnj Alib 
tubcILu i>r puBflln. Ttirn Ift aia|il« room for motile or«Bii> 
luDii ro nrnim fttmiti In eurb a (ir^pDnllird. fttid ttir lomi of 
Dt>illl1r tttclilc-dt to Bn^urtiialioii ■■ rrtilllr obftcrvtil. 



iiBiial to ham 1 
bacttm, ia OT^er to 

bMiUi Ml* ^glidteM Mte* Off 
ilmld b« iktkm tbvm^r Mm te 

iCOOOpiWPW Vita CDCs IK'IpUUfW M ttv tjfiPUHl 

badUui u4 dtolerm vttiria. moCiW o irgmi—i t, Inrt 
trbm di^ fTOv in di^Di («tnp(oroonu) or in 
cobcmt tmmm <dipfatlKn« od tibcccte faanlli) 
sort Tteknt ■<««« most be itw rtrf to^ IHilr 
rfiakiqg of A ti^oid mltunr of the dipfathtria or 
tubodr bttdUeu is UHj dtrvtiv^ bttt Uv Bwdinm 
m^ui be paaed LKronsfa a ptiptt filter Won it c»o 
be Died ffLfety; to thi£ w^t the kf^ dtmpe tn 
rtinovftd. Socio iQvo«tig«U»r« dn' o lorgt qtuntity 
of lutwrde faM.-i!}i, ^rind ihrm c;p Uurodgbly la an 
ogate a^orUr and Mspcmi tbe parttdes id salt 
«olittioii; tiie Ingmccit^ conditkitt of tl» orgtn- 
Uma do«» not interfere with their portidpatioo in 
tfae racUon. One ehottld have a uaifonu tedMUC 
in prcpdri&g a bacterial ciniiltioa in order to obtain 
10 morl^r aa poasible ihe tsme nambvr of ba«t«m 
in a given volume lyt Kiiuiloit, on different occa* 
aioiu. For example, one may noiformlv fiupend 
a tvrentT-four'hour nptr ailturv In 10 v.c. '.\t «&U 
BoLation. A luiifonn techfiic makea it poaalblc to 
obaerro the quaatitatira relattouJiip uhich exiHa 
between the mam of baeteria (o be aggLutinatcd 
and ttie agglu Una ting paver of ihc Aenua< 



To OhilBlii 


To obtHJil tteruni fur the t?Ht one may rOMrt to 
bliatcriog; 'piact a cnnUiaridcs plA9t«T from oti6* 
half to thre&'founhfl of an inch tquarp on the nb- 
iluiriiiDLl i^kiti, prolDi-'t tt wiUt n dre^fliiig. anij in 
nbout twelve hour* remove the *crum with a *icril- 
ized hypodennic syringe. Or^ orte may collet in a 
small tifjti: lube from 0.5 to 1 ac. of hlvod from the 
Idhc of the par or fiitgor-tif , aad drau- of! tlj<* wnim 
after u liaa «epcir&t«<j by clotting. It ie Uie cm*- 
torn IE «ome ircl I -equipped Icbomtoriea to fill icv* 
eral tT-ehap&d capillary tubee vith blood from the 
lobe of Ibe nar nnH In *epr*rnto tin* blood from Uie 
wrum at once Ij cciitTifu|;ation. The custom of 
dryltig & iow dropa of blooi on a ooveT^la^ or ou 
nilcr [m|»i<r, hiieI of Handing this pn?pura1ion f^ n 
laborntorr for tb? aggLntmation reaction, baa been 
praoliced quite extonalvely, and i« n juiitiiiable 
priffwlum whrii it is not possible to collwt the pure 
eenim. It liae the diatidTimtapc that the experi- 
menter never know« exactly how much blood h» 
bwn collected^ and conaeqneutly caa not perform 
the tcct vith cxai;t dilutions of tho scrum, the im- 
portfliire of which will tf poirted out h^hvr- The 
red corpuflclesi and d^jhriti in such a preparratioii also 
intrrron> with the clcamcfls of the field in micro- 
scopic examination, a fliflPcTiTt>' whirh may be 
partly overcome W filterinjr the diwolTcd seniin. 

When only a flmall amonrit of wcmm h flVAilable, 
it ia nppewary to ii^ tire microscopic method. 
Nonnfll hiiman *cmm, when concentrated. Onnd 
^en when diluted to one in ten or hif*her, somo' 
tiini* n>?Kl^*l^hiat(^!4 th(- t/phoid Imf.illii^ Jitic) jmmr 
other or^niftms; tho some wnim, when dihilcd fo 
one in forty or on* in sirty. may not agglatioatc. 
The acrum of a typhoid patient, however, or nf o 



IhcH hijglicT diliiticffl&. It is ^rticmJ^ hM Qiftt 
ft dihitiQik «f one n Urttf or ftfty is w U Bc k a tl y 
Ugb to cdlminito tbe pe^l% of igglitfawtta 
kj ft iMft'tTpIioid «cnsi, ud 8iifflcifttti:f livw to 
ifiiid«r tht eerutm M ftU, or acftrhf all, trphoi^ p«- 
tiofts iiSg;lutinitiiig:- Tie neceBsitf fnr ililulion of 
tfic sfmin ift eiapbaaced bj the ftdditioOMl fict 
itai infeeitoDS Tith rdfttod oti^uiisma, u tbecoloo 
badlliut, cftnw ft vli^t inrtvmii to tha »ggintinftt- 
in; power for the typhoid bactUtu ftloQ£ with ft 
reUtitelj Urge ineniM of colon ftft^ntimiiiL A 
trst With s low dilution of this oo!od Bmtm nlglit 
pvc ft pceftivo nftction with the tvphoid bocittu 
ftud Itind to m incCTToet mtorprotation ; but 
it ft dilution of one In furti were oaed, tlie doel< 
seslQtisfttioti of the typhoid bodlluft vonld wpook 
ftgiinvt ft ^rpboid infMtion. Thia will he condd- 
ertd under *'sMup ftj^Ktutinatioir' (Chaptrr XIV» 
A tonvtraitat method of inf«3imng eniftJl 
ftaouoCft of culture aiLd Ri^mm it br mcAns of a 
Ann plfttinum wiiv vrlndi i% VdI al iia Up to form 
fttt eyelet or "loop^"* If one plftcc^ one loop of 
tttmia into a imftU watch glosa cr hollov-groiind 
slide, snd n^dE ninp Innpv nf bouilloti or of unit 
'eolution, a dilution of one Id t4*D ia roachod. Five 
loopfi of thU mixture with Etc of the diluent giv«i 
A dilution of one In twenty. One loop of the sec- 
ond ditnticn, to which is added one of the cuUtjie 
ntspencion. fpvet the df«ir9<l Hilnlfon of oni? in 
forty. "Hie liiht uiay be miiwl clirectly on flie 
coverg;lflset and then inverted on a hollow 'j^round 

a. rfflffn InlrodaE'ril • 4«it«aMoii4l *'tMp" of 9wh 
'liiii«»loB* 1^11 It lii>]<l> 3 nLlllcrtni« of bacttrttl nlla m 
nbtj orv utfa tnm • vdIIiI mrfar*. tlk» tbul of ifU. 


SSFKCTWy ASV /.tf.W/;.V77 1\ 

slide. Mr^r^ ec«iirst< diluttans cmq ha mide hj 
mttUi» of Mpilliry tubcA. 

A convenient amonnt of fienun is allov^ to 
tnUx the tiibo bj eapUkTjr (ttmctlon. Th« length 
of this ixilumn U luarkei] on the tube aud tlteii 
euc<M!asivi7 voluni^s of tbo ditiiont drawn in, vacli 
being sepsrsted from Ihe «ticcGedtn^ oni* hy a smali 
liuttlflu (jf ujr, Tf LH iT-iidily Mn?ti Ilow with rvrn n 
minute quontit\ of Krruin, one may rflake the ttf*t 
with dilutionj; of ono in t«n, one in twenty, one in 
tliiiiy, orm in forty, etc.^ di-tniU vthyrh aw nw-M- 
eatj for u i:orrei"tly ptfrformeU tr*i. It is im- 
portant tbut in the different dilutions th« uimo 
iimount of bactcml *mnIsion be need. 

Tn tbp TTHKimfiropic b^st, mofo Benim m nAf*w- 
wry, though tlic quantity npod not be large. And 
the dUmiona are made in lest tubes of suitable 
nm. One ahonld alwavE <1eftl with definite qnan' 
litiiw of the SGritm dilations, and ghonld a]way> 
&dd the aame amount of bacterial (^nmlsion In tlic 
TflrioBB tnbe£ involrod in & test. 

If flgglnti nation <»ccurs in tlit mk*niifi<?o[>3c preji* 
nrivlinn di^cnbtid nbo\e, one nee*, with the high 
power, in the courao of from fifteen miniitcji to n 
half-honr, that two or more iniero-or^aiiiamK 
whidi vimie in cijntutt have a ten<3eney to remain 
in this poeition- In the cnw of a motil'* ore:aniflni 
(typhoid) tho movemenU may be ejcsggerated for 
a tinw. In llio course of the next few hours, other 
cella&re abided to incipient groups and new groups 
onpnnlc. Motility becomes lese nnd Iras and ovent- 
uolly ceaaos, in a cbaracterifltic reaction. The 
maximum change hva taken pUce in from aii to 
eijiht hoar*- Not Ic^ than four or fivr cells whieh 





toe porman^Dtlj flf^lutiDBted are connd«recl in- 
Otcatm vt ■ positive rejiclioni the U^Mi i% mo»t 
dodwTo when furj^c mneee? arc former!, bo kr^ji? Ihnt 
they ar9 swn rea^iily ^'ith & low m*i(piitif*al.ion. A 
Kimilnr jm'fmrnHcin to irhicli no wrnm Iiils been 
added ehould aJwa^s bf> madi^, in order to oUminat^ 
*pcntiui<K)uii or "ntito-a^lutJnntion'' as n possible 
ftouToe of error 

Til a mikcrwicopLc iesU tbe Tiniform cloudiiK^f of Tti* uni-m- 
th^ miJrtijre of fcmvi ard bicteria become* 
changed bv Uic formalion of amalTcr an^ Target 
flfikea or L'lumpa i*f bnHorin, whirfi in the course of 
ft it:vf houm 'ink ta Ihc bottom tiA n white precipi- 
tate. leai'iTi^ fi clear overlying finid. Here aleo n 
ronirol t«hi\ \n ^rhJrh no H'n:m has breii /idcli^rt, 
should be preaerved foT c:anipansoii, 

Ttt body temperature, nhich may bo obtAined 
in n thrrmofifat, farilitntes the reaction, 

Tlir vnlut* of nil ugt'lutinfttiiig epruni ojin uol te 
cxpreHM^i in unita wJtU tlie exactucfts that ia al- 
tflinod m m«iuunng diphtheria aittitoxin for tho 
following n-jifloiiB : 1, Tla- limiU of the n-nrtitiu ate 
do: aufficteutly dtilnito; i, a givm niasfi of bacteria 
haj tho power of absorbing viir^in^ nmovint* of 
ihe agglutiDfltiog suhatance^ depeDiiicg on the con- 
cmlratioa of tiic latter; ond 3, it ia impoaeible to 
obtAUi Btaudard baoUrij^l emulsions. 

Oiitt may o-rbitrsrily d^^Ldo on a unit timilar to 
tlat of Zupnik, in tvhioh a. *<<rurD which in able 
to «L£C]utiiiate t ^iven maee of bactcna in a dilu- 
tioD of one in forty w UU&n as th« etandard. If a 
nmUnr Amount of ii )M*rum n^lutinattv in a di* 
lution of I U) ISO it la »aid to be of tlireefold 


isrKCTJojf Ayo mituyitr. 

Tilt rftlue of lite agglutiitatioD reaction aa a 
clinical diaj;iioftbo aid will be coiuidorcd Uler is 
cgnnection wjtii the iiidivitluftl diseaaea. 

A coDsidcTCitioD of a;>glutiQ&tion voul^ he in- 
nampM"! if our. did tvst rneutioti Uie pht'inmi*Minn 
fi£ it occurs with cells other th&n tho«c of bacteria, 
in particular the rod blood cells, Tho serum* of 
miutj aniiTftls* u stiiteiJ in a prerioua chapter, nnj 
toxic for the crythrooyt« of some otliOT epoci+w. 
In acme inetanc^^ the corpuwlcft l<m<^ their hemo* 
globin under the influence of tlie ftoium (hcmolT- 
Bis) ; in othor inatancfia, or ffvcn with tJ^o &une 
flpniine if previoiisty he«tin], tht tTirpuKth** nr** 
tLro^vll into cluuipa nntl settle to ihe bottom of tlie 
ttst tube, Icnving a clear ovr^rlying lliiid. The 
nnabgy wilh th? bBclerial agglntmiTis goes sHll 
furtticr, in view of the fact that th^ formation of 
tlifito "bcmn^lutinine" may be induced nrtificklly 
in Hie boily of an miimal bv the injpction of 
cn'thrtjcytc* from another species- An animal 
doeB not fonii afyilutinine for itt own cells (autO' 
ng^lutinine), birt- often doe*;. hawe^Gr. for the cell* 
of acothei member ot the san:e species (iso-ngglu- 
IJmiid). What E»^ enid in the next chapter oon< 
ccming the specificity of the bactenal dgglutminfl 
abo hoHs for the Iiciuagglutinin.^^ 

Certain plant toKins, tmo toxins with hapto- 
jihoroua ami tooplioroua Btnichirea, ngglutiiiaU! 
red bloofi ccUa: ricin, abrin, crotin. etc, 8omc of 
th^ wtrlioft and mort important work which 
Bhrlicli haa done in the (Ic-IJ of immunity wm ttc- 
compliaheci with thoflc plnnt toxina. 



Tiro siib«tiuiceB ure concerned in agglutination: 
<>De, tbd ftCtiTe or agglutiuatlng siibaUnce, trials 
in tho Mriim, irhitc the othcr^ the Eubstfinoc aoted 
on or the aggliitinnble Biibatance, is present in the 
bacterid. Tlie agglultnAble substance is generally 
iiippofod to be piueivo in the roaction, wljilo th« 
agglutinating' property ai-^ma lo [X)Sde^ a feniieiit- 
HIw dement, which acta or the ngglntinnble sub- 
stance Agglutinm, the term Ksed in the prwed- 
ing ehnpter. U n^w generitlly applic>il tn tlii^ iiub- 
ftance in the Bcrum. Recently the hacicriai con- 
ttituent t»H been called ae^lutinopcu, Wause of 
th« hit\\v.i thnt the aggfutiDAhle tuhfiUnrn, whrti 
introduced into t!ic animal body, sUmolatea the 
lalter to the formfltion of Bg^ibtinin; hence ag- 
glutinogen nteniiH, not ngglutinjit inn -producing^ 
birt o^lutiDin-frodndnj;, Thwe ehorter tsmu 
will be used for the? saktf of eonveuienfw. 

The {[jreaeuce of agglutiiiogen In an organjsm 
miiT be dcmcnstrateri in three vrtj»: 1. The mere 
fact of ita aggluHnabilily by a s^nim is eTid«nc« 
of the T>reaeace of an agglutlnable Aubiilance. fi. 
If dnring tnfoctioD or immunisvation tho «oniin ac- 
i|Uins Agglutinating properties, tho bfi('t«riLim do^u 
acMea «n afffflutinogcnie enbatance. 3. Tf a onJ* 
tnra ia mixod vitli a ^emm containing th? tpooi^ 
ag^ntinSn, ar^^l B.her a prior! of contact la r^ 
Tnorcd bv ccrtriFii^tian, the r?«ultant ditapp«v 

A VbI m I BAiB^ii , 


l.\^tiCri{^N Af/D iiitiVMTY. 

Of Al 


ancG at oggliitinifi from the wmm. wbicli may lie 

demoneti'&td^. ahowa that aomethinj; in the bo& 
terifl (aggliitinng«n) ho8 combing with tho a^- 
i»i.<tib.Uf»> The location of agglutinogen in the bacterid 
oullif liu rvcdved some dlecusaion. There ii n tend* 
ency to believe that it exisU in Iha cell envelope or 
p&rhaptf on its Eurfflcc. Jt nppoflr* lo Iw formt^H in 
ih^ cflll, and, in sonie cneea, it mav be eicretwl into 
A vurrtiuudiNg medium; t'ertaiulr when bact^ita 
die and diaintpffratc agglntinofccn ia libernted. The 
fiHrat*« of certain cultitres (entirely fpoe from 
^larterial cells), when injwleJ into animals, will 
cause the fonnation of a^lnlinin^t. Aluo. juett as 
a miCTO-OTguiiam ia Able to abuorb a^^^lulinin from 
Hin rrtrn>Bp(»nfh"rg nnfismtm by n p^H^e«! of 
cbcmirni union, eo n i^trate of the type mentioned 
U able to ucutralize the a^^luliQiitins power of the 
eemm In these mstnnt'cii, aggJiUinogen bwfunflii 
rref> nn n. vonBet\\ietiiye of JiHinle^ratloii vt mm^ of 
the bacterial cetla. 

The laltrtilce of certain cultures esliibit another 
phenomenon when t.hcj an' mixed with their spe- 
dftc antiHeniEii* ; thin httn to do with thtt bacterial 
precipitins of Kraita- If, for example, Ihc filtrate 
of an old typhoid bouillon culture is nii):ed with 
HJitityphrid wrTiim, a diHUn*!t |jrecipitftle is furmwd 
which eventuallj' «ettlea to the botlom of tlie tube, 
Thii is a upocirie rcaclion, and doee not o(?cur if the 
Altrato ia mited with aome otiier Jmrniuie »erum. 
It ift thoviglit by come that this so-called prccipi* 
Ubic mb^JLuce in the filtnite is fdculiraL nilh the 
BggluliiifibTv nbntanoe (a^lutinogon), Uut thia 
point ii- sUll the tubjeet of Snvefttigalion, 

Tic rrcclul 






org&aUoia by chemical procc^eca. The presence 
of the tubftimeo in tho vxtrttcU b«com(^ niAcife«l 
wbpti mmiiniiwtion with tbirm causes thf; fDrniJi* 
tion of an Af^luttratmg flerurti. Thia, again, \$ 
tho "twt of immum)ciition/' 

The Agglutinogen of one baclerhiin is not ii3en- 
ticol iritfi Uiat of nny othor. If thcv 'ivcrr idcDti- 
cal, immunisalion with th* or* wonbl yi*3H an og- 
^luUiiutici); nurum (jf w|unl |Htwer f^r bnlli cdU; 
thiB, howcTor. is not the result obtninf'l. On ihc 
oih^T hancl. the n^lutmiTtfi of two dilTerent orj^n- 
iftra* may roincMc to n ctTtAiii deffn^* n^ will be 
•hotwn undfr the subject of "^otip a^Iuti nation. ** 
Certain exjwrimMit* jp> to *how tliat Ihi* cif^liitia- 
ogOT of ofTi n *in^k miCTO-or^aniKiD is nut nni' 
form Aub^uncc. Ono portion U host-euj^ccptiblc, 
bdDg destroyed at R:? C, velille AiiotTier porlion la 
■ud l« r«i»t & tetnperfttiirc of 155 C, Sucli (cch- 
oical ^iiL*fitions oontimi^ to ba invt^Btigntixi, 

A^utioogene are a&i<l to p&sa throiiglj i^-mi- 
perm^ftblc mombrflnM, while a#;clutiniii» do not. 

Smith and flrngb cliiitiTigniib two Umtln of n^- 
flatinogeo in thow baotfria vfh'ich po^<-*3 HngelU, 
ODD peculiar to tbo coll W1y> nml Ibe othtT to the 

Agglutinin m«y bi? prixipitntccl compld^ly froTi) 
a 0enim by the BulpbatoA of ma^ncMjum or amm^ 
Qinin, vhcm Uio fdfc* ara uwd in proper coooentra' 
tione. BecauBc of their rcachon to luch pr«oipi- 
ttting tgtatt, Agghitininn nra thought to belong to 
the globulin fraction of ftjrum* ; vbetJier ^lobuliDd 
or not, Uic^' urc preclpiUtcd with them. 

A^lutinim rvt-hi f1ig«etion vitb p4*psin and 
papayotin, but arc Jcvtroyed after pmlniigcd u* 


riHK^ilnt and 

■ llllllKk^Vn^- 

rrspvrilva nf 




potfure io llie sctloa oi tijp^. An Agglntinttin; 
Bcntm which if CtM and kept froo Irorn mr>iflturc 
tud th© ftdiOD cf light relaina iti power unnltered. 
Simil&r to a^utinogen, ag:glatiiiin is UiQu^htocvt 
to be A tmiform eubetsnco^ one portion being sus- 
ceptible lo hejit, aTti] nnoilH'r portion rwfftBnt; 
thfM hare been called alphs. tui'l bet^ a^uHnins. 
It ia eoQvenieut to speak of Uic reaction betn-e^ 
Agglutinin HnJ >i^!ntia(igni, nml of iht» pmcesa in 
the body tlirou|:h vliich agglutinins arc formed, in 
terms of the eidc-chniri theory. Atwordingly, if 
Uifit conjH(itiieiit of micn>-*>rgrtftism8 wMch we Imve 
lermed agglutinogen is the Gubatancc which slimu- 
bC« the ti££u*fi to form aggluttrLin, wo mnst aa- 
dgD Id it a liaptoplioroua group throuf^h which it 
may unite with the receptors of the tis^ic erlU- 
Thi» haptophorr com4« iDto play again in the union 
hetwean a^^lutbogen ajid agglutinin, which pre- 
cedes tj^lutination. There is no rcoeon for aa- 
B^^iog to agglutinogen any other ^tmctnre than 
thi* sin*rlc hnptopliorc; it ia a passive borly, similar 
to antitoxin, and has no otb(iT function than that 
cf iinitinjr wth^T with cell or with a^lulinin. 

Airj,-liilijiin also rauri have ft haptcpboroua or 
hindinji jjroup, inasmuch ae it cetera into combina* 
tion with ngglutitinj^i-n, Tn aiMltimi to thid bind- 
ing group, experimentfl haro abown that a^lutinin 
pcnCeEOs a toxic con«tttiient, which la analogoua 
to th<? tosnphoroiis grorjp of thfl tosin innlecule. 
In this ca?c, however, it ia cflllod a zymotonc» 
TAinophorouft or ngghitinophorous proup: euppofi* 
cr«pp. p^uy jt 1,^ 5 fernienUHItc activity (Fig. C). The 
analogy with trjinui ^aco forther, in that the 
zymotottL? ffrojip of ai^!iit:n[n may dep?iicrnii? or 
maj be destroyed, IcaTiujf the haptophoroua group 




trith iU binding powor for agglntincstti practi- AK»in<in*iit« 

tally uiLftlten-(]; thebe are a^latinoid*, ju«t nft 

toxins frUen clianged in n eirailtir xraj^ euro caUod 

toxoid*. A wriuu which ia rid^ lo agglutinin may 

be changed iDto one rich ia ogglutinoid by expo* 

sure t<> n temperature of from GU to 75 C, and by 

tho actton of noids or 8lkBli«£; thi* diunge altto 

takes place aponUneousIy in the course of timc» 

vrhen tho agglutinin ia in solution, 

Agglutinoif^B nn* dr>t.prtiwT by meth*n!» &iiAlogcti;3 
to thoa& naed tn Uie recognition of toxoids. If 
toixoids xuiite nith all the aiititoxin in a colutioL, 
there naturally remains no oEtitoxin to iinitr with 
true loiifi wMch may l>e added Aubae^iuently. Sim- 
ilnrly, if nil \)\ts a^Iutinogan in a mnu of micro- 
orgBniaiUA lia^ uinUd wilb inacLlve agglulinoid. 
afEglutmin which U addofl aub^^iiicntly would haw 
no point €\i fittflrk nnd the reaction of agglntina- 
tion would not octrur. So we may aay that irhen 
bflictCTJa ore treiiti*fl with a eenim whicih bin lort 
ita original agghitinnting [lower. an*l the bartenn 
are tlierelfl," made frmuiMN^ptible to tJ»e .tction of a 
fre*h aggUitinatinc spriim. tbo fonncr aonim con- 
taina agglntinoidii. 

Sometimes H is found that even % freah serum, rroAv- 
when concentrated, will oftiwo lees o^lutiuaUon *'"' »«"-'•' 
tlimn whfn iHlufRrl, Tliis Im* ln-rn rrfrrrrtl tn the 
pretence of agglutincids which have a stronger 
ftlKnily for agiflutinojTon than hiu the npsli^ttnin; 
vhm nf ihi* t-hsnirirr thpy nre esHed proaggln- 
ttnoids, and accordingly are analogous to the pro- 
toxo^dii mant^oncd CArlior. Aa the aemm it dilutvd 

tb^^ L*iiHj:i'utniti<»» rf \\\f pm'B;L'gliitiroid* hor-'Hiit^ 

lesi, and at n tinie when Ihey arc eo dilute that they 
htTt no influeiKe on th? reacHon, the aggluDnfna 


i.yhlXTfM AyiD iJUMVMTT^ 

trc itiil preheat in tudi qoantitj th*t iggltitioa* 
tion is br>iJgbt ahont. 

Tive preticijce of tmuic mH b ntfciM&trj for Uic 
occurrence of A^btinatioD. Bordrt £oun4 th^t 
if the salti were remorei from the aerum and from 
the Auapen-iion of bjicteriA by <1ijil)-n(r jind Ihc two 
were tlicn mixed, a^j^lutinatioii did uat occiir; if 
a jirnall trai^e of BOtlium ditortd vuk ailJed tl^i^ m- 
ftction toolt pincc piomplly. Furthermore, if the 
e^rum w&8 conipI«t^Iy rdrtidved from the bacteria 
by n'firiiliHlly w^>*1mU|>t tliitm in di^itilliH? Wftii7r, it 
was foiiDil that th? microbea h^ absorbed the t^ 
gltitinin, but tlie Utt<rr remaiaed inaelive until the 

Thia cipcrimcnl not only auggeatd a Jiaptophor- 
oufi /Li iIi[ilinK"»?*bwl from a i^rmotoiit! Kf**"!!- ^^^^ 
ftlfo indit^ixtna that a£:^Ktti7iatioii coDaiats of ivo 
piiaSK. The fir^t phoac t-cprojionti thu union of 
n^^lutiiiin vrith tlic bjir.E.rHn, wMIr in tli^ ^ecofid 
arc included the other clianjrea necL'**ary for the 
clumping of the crgauiAout, in wliieh thu actirity 
of the xyuiotoxic group is rcprCAcnted. Tlio action 
of the tvali, jufft cite^. i» uukiio^fn. 

The propertiw of aeniras which ar^ of intemt 
iu immunity ar<- now Iw-ing ntuiliwl by dieimata, 
notably by Arrhcriu^. The Attidy of rnitM action, 
of chemical oquilibriuTn between agghitiniTi and 
iiQintiiiotJCiit for exjtmplfl, and of the diseociation 
of the eomponnd after it hae onco forraod, ara 
ixihjwti un(h*r Bttv«Kti;;allon. hut vUich are too 
tivbnirni In he entrrc<J on her**, 

"Group flR^lutinnlioti" haa been referred to. By 
t^iia is meant the ability of an antimicrobic aenun 
to a^lutinate ct-rintn otlier organiami wtijcb mor- 
phologically. biolo^calJy and oft^ pathogontjti- 



cally, arc doe^Ij related to the homQlogoua bu* 
tchuin. !u th«tiO LuKtanc^^^ the AggLatinating 
power is gTcalo*t for tho h'>rHologou.s org&aiam, 
anU tlie ilifgreo to which llic lictcrologous crrganisiaa 
ar9 oggLutinatcd i%, to some extent, an index of 
Llie pruxirtuU of llie rdiitionsliip of Oie IMter to 
the formtr. Antityphoid atrum lie* bccu fcunil to 
flggldtinato the psittacOHi*, colon, paracolon, and 
paraLy^ioid badUI aixd Buciilua entcrUidU, but 
the action la ncTcr «o fltrong as on Lhc typhoid 
haeilll78 itself. We are to iinrkrutanfl that thU 
power in a^luUuatc rulatwl organisms repreaoiita 
ioin«thi&g more than the normal property of the 
wrum; there \\ss Ijeen nn ncliia] incrGnse in agglu* 
tinin for the betefologoua bjic(cru us a result of 
inf«otion or immuniiAtion by the prin^arv organ* 

Tfavirj; typhoid fcvf^r in mind, thia in n ride 
which workB both way*, Irfcctiona with the colon 
baciilua and rtlalt^l or^autsmH. jLud Homi^EiEnt-s 
with orf^niLljimff not clo*Hy relntcd, a* the staphylo- 
:^Trcii<i. may <'ait8e an iacrease in agglutinin for the 
typhoid bacilluiL Tlie importance of tliin fact ia 
OTidont. and it moy (rploin Iho posilivo Onibor- 
Widal reaction fioiiit'tjiiie!^ fuuiid in infections 
other than typhoid, 

Inaamuch aa tho highest agglutinating po^^or 18 
alvTQ^i monifGct af^Ti«t th4^ hoirinlngouft orgaDicni, 
th[i U »pokon of as th>: chief ajni^lntinin (llaupl- 
fi^gltitinin) of tJic »MTim. w!dl« th« weaker acpliT- 
(iuinn fnrolbpr n(vn(it«mi* nm pn'lml pnrtin! nr ad* 
vrnlitious aggrlutininj, or coagglutiniaa {Mitcff- 
ff in tinin). 

Tlic phwiomcnnn of gronp a^uHontior \rnni\A 
•Mm to violate the «iieoifteI^ v^h ire are in the 



lijFsvriox AKD t^ut/siry. 

habit ot aitributiug Id ihe rvaoUi^iiit of immuiiilj ; 
)'et B reuonablc cxplanAtion hot bnoi olTcrvd for 
thfl occiirr«nc^&. It ia probuble that the proto- 
pinaiiui uf itll <vUs liJiVf; eL-r(nui L^uruUiuiTnU iu 
common, and that the closer the rcldtionship bo* 
twcen two fltfterent ceUa tlu? greati^r is the siml" 
larity of tlitrir cohkUIucqIa. In virw of thin prob* 
ability, PiiriiGni ban ueofl the following illii*lra- 
l[on la tliv vipknatiuu of ^loup ii^^gliiUiiaiioaa : 
The typboid hncitlus conUina ccrteio coDrtitucsU, 
ngljliitiijggcnic mo}cculo3f u'hiob ono may <lMig- 
ciate a^ a, b, o, <), and e; t];i»e itilT^r among Uiem- 
i»el\on ^11 unknown Ti:jr|^c<:U. I>ut «ttcb i^ able to 
iitiniiilfttp ti> tbp foniirttinii ftf ft cnrrpsponding ag- 
gluliniu. TJitf semtu. tbeu. tti»uhl liiive tbe ag- 
^httinin cnolcculnt A, H, C, JJ tui<i K, nUL> differing 
jiming OteniHelvw, bnt hnving at lenst one property 
in comiuou — tliat [if uiufin^ a^^luiiiiAlion of the" 
typhoid bocillua by imiting with the corrojipond' 
ing nggliitinogenic moleciiloB. In tbie »pnso noth- 
ing coui<1 bp more npL'cific- The lifinllui enUri* 
tidis, doeoly reUt«d to tho t>'phoitl oriranicni, may 
pow««!< (lie ft;;j^'hilinopenic riKilptrulea r^, cl, e, f, g, 
and li, and MhfsinK tbc principle nxprc*if^:l above 
Kfonld fttim\j|ate, in the body, to tbe formation of 
the iiKghjtiiilti molcruh^ C, D, E, F, (1 ami H, 
Inamiiicb an the afifihitinojicna c. d ant? c arc cowi- 
mr)n to the two bacilli, the fLfrghitlniriB C, X> aD^ E, 
whiph nri! present Jti both iHrnimn. would aUrct 
''ither oT the two or;*niiiBmB. The typhoid etniTn, 
how(^'fr, wooiM contain fivt? a^jCrlutinin* for the 
typhoid bftcillH* and only thn?c for the DaciUus 
fnUriiidii, oonsf^qucntlv tlic action i^^uld bO 
utronnoT n^inut Ihp typhoid bncilliw; mvtclo fn*i- 
/nri<?iiE. the sniiv^ applit* t'> the fiili'iUldii *er»in 



1\i!t B^uie Udl' of ruflMnin^ widIiI i^tphiii the In- 
crease a^lutiDftting power of nn nntJcolon ^uruEn 
for Uic n^hoitl bacllltiff. 

A further cUbor&tion of this principle maj be 
mftde in & caso iq which ti^o diffi?r«nt etrain« of 
i\\v unic or^nriiKiiE (Uphuiil beicillua) (mv^ (suiiie^ 
what dilTeKnt agglutinogen ic moleculca; ronse- 
qacntly the. homologous immone eomina for thd 
Iwo nr^mxEKH mij^ltt nut n»inriil« iu tlunt Jig- 
gluticating powers for a third atroin of the badl^ 

In vi&T of the pinU meationaJ, it i« clear that 
■peciAcity of a giv«ii mrum jnny Im determined 
oolx t>y diluting the 9enLi>i to eucb an extent that 
the cooggtuUniiu proeticaUy wre eliminated, the 
chief Agglutinin being prcseat in to much greatT»r 
eoocentratjou tlut it la etill uble to uf^^litbunte 
the homologous hnrb^rinm. 

Thporrticjilly, it is aloo importftnt for t)ie spo- 
ciftcit> of tlie I'eii'-lkin th«t tUt [(iirlitriilnr wtralu 
of the oTj^Aiiifm to be ti«j(l for tbc test corrrapnnd 
in it* fl^httinognnif m'tl^nlea or receptors with 
tLoae of iKc tftmin liv,-i] frjr the imniunixntLjn - Uti: 
^Intinogcnic rcccptora should bo typical for t}io 

It li doubtful If group agglutUmtJon oceuv* 
Among all clcwrly rrlMH barfcTia, iDasfriucli a^ 
Kolle found that it did not esfiat amooff the vib< 

It ia Uiought possible tbnt the multiple aflfilu- 
tinAtinic powiT of jv m-i'ijui inny hv OJiiiHRd liy miiml 
inffctioiu in «oxnc innliincc^, Althoujfh thia is to 
he kept m mind, one )thf>uM not oTerettimato \U 
diiiKi>oittif7 impuitiuur. bix^niiiw ji HimiTar innlti* 

fiapcprlABO« v( 





plicUy may reault from infection bj a auiglt) nticro- 

Tlie ejcplnnation of the prcduction of agouti* 
iiJiiB by tlic body, acconling ta tiie ooiw«ptioii of 
Ehrhoh, ifi Aimilar to that already i;ivcn for tho 
pniiliK'titm erf ^.TLlTloxinn. That \fi 1o sny, the a^- 
glntmin molecuJcs ^rc cdet-oCT cell rvct^itons thv 
cverprodticimn of lAhtcli hn« occurred as a menh of 
thc:r UEiiiin wilfi Uu* ngglLiUimgerjir mo1eciile« of 
the bacteria. The autitoim receptors were rela- 
tively linii^lo, having no other <i«iaonfitrab1o ^Iruc- 
turi? tJian thnt nf Uie haptophoroiu gn>upA throii}|,'li 
wbioh tJ»<yf uoitc with tho corresponding toxin- 
Wc havo ivrogni^c! in tho agglutinin receptor tvo 
oiii-r. groups, a Ittptopliui'OUfl and a T^moioxic; t'Onatt- 
queotly it muet linvc this nninc stnidurc when it 
10 still a part of the rpll. Ehrlich designates U as 
a r<?ceptor of the scfoiml onlt^r ^vliidi, ln-iii^' i1<t- 
fincH, i# ft roccptor m which a haptophoroiis and n 
lymotoilc group exist as Iclegral parU of the 
iDoIecnle (Fig. G). 

Id accordance mih the eitle-choio theory., the 
shilitv of fin aniiTifll ti> form ngjihitininn fnr a cer- 
inin orgnnisin would dtpeml ou its possewion of re- 
<^ptore of the* second order vrh'icU are able to nntt4f 
with the aggluliroff»>nir rwepforK nf Ihfl bflrtpriiim 
Tt j» vdl crtnhli»hc<l that difTortnt animals niav 
not fonii wmma with c(\nn] n^c^ntinatin^ pnwflr* 
for an orpfuntftrn. The rollowint,' U a coT»<rrete ex- 
ample: VTaascTmann immnniMi! rnbbita. iniinea- 
pijta and pi™eons with a strain *>f tlip colon bacil- 
Tub, and tPKtinl th^* thm» frriimn with fifl'rn oUier 
rtr^na of the same orpiniflm. The «crum of the 
jruinca-pi|r« Tvndily apfflnlinaled the «rain which 
wfts ufled for imrrtiini^flll'in. hut Rcnrci^ly nfffcW 



Ibo otiiors. Tbo icruitia of th» rAt>I>h6 nnd pigeoiu 
nUo ngglutiiiAleil the hoia^ogoua cullure. biJt the 
cmg^lutiniii^ vliJch Ihey pOMeatMl (lit) nor .ifTo(>t 
other Btraiu* njuullj. OciD^iiviiLIy, it vta* puf*- 
p(»cd Umt thtf odU <»f the three animals t*>n(ain<;4 
« limitr*! iiurntipr tit mi-jikus ill L^uijuiiua^ whureii* 

F^- n.— 4in[>1il^ rvfirruiiliKlon cf n«i>#(klarii of tM tfrfVHt 
«r4vr anil of >odi« (ubalmtor iinJirDji *Mli rpQt of Tbrin ^j 
^'*ll rorrDmr nf (hr «n-nni1 nrrli'r: tl. iriinphnr* ur t/mopliQ^ 
#■!■ ctnap ^' 1^ rfi-cpcot ^ f, nApioplitirD oi tQ# m.TpiDi': f. 
fMNl MiMUDn or urndurt vC mi<';»rliil OUlDL'EiiiLlob utiLiIiiE 
villi lb* liHplv^ibvr* vt iha »JI truiilur. Ffviu tShilLJi* 

ni. HIL 

Oth^ receptor* irhich it'or^ pro^ent in one of ihe 
AQjinals verv largel^v ^lontiDg in the othvr two. 

laagj-laCJDabilily vaa tnentiooed na a charac- 
tiffblir of c«rl£lii baoterra. ^pocrially tliv W^IUtu 
(vf FH<^^<l]andi>r. Thia condition ia miKli m^re 
iniporlnut when it InmlvM nil ^irgaolam vhfcb 


t^fPBcrroy avb utMusnr. 


muolly » oorluliratcct mih tuo. In aome fn- 
ctiiDOcii. the lyphoid bacitltia vhcn fT««h1y ctilti- 
vatetl from a patiaU. or, indc!<K), from conUml- 
nait>A water, lias been foniu] ia roiet a^lutinJition 
hv ii »troiiff »-ruin: tW 5nmf» orgianiem after a 
perioiJ of existence on artifK^ol mwlia Wfmicw iig- 
jdntinAbJc. WiclaJ tud Sicurd noted thftt often tJie 
Aorum of a. frplioid patient would not iiprirlutinato 
llip hnriJIiiH wliicb )iiiil Wn culLixalod from Uie 
pnllent":* nnn body, althon^h the *anic scrom 
would n^luiitidte laborutory oultures. Cuitivn- 
tion of Ihf lyphoiii brtdllns at 42 C. will cause it 
to loM it* mj^kI tit inn tile prciprrtv, hut it may be re- 
odabliAJiciJ by aub^ueut cuttivalioii at \ovir 
tcnifK:ratnro«. Tt t«ems that thie varintion mnat 
be i^j» iu Kimi* chwi^' in Ihi* bju-Jem, i. r , in ih& 
fi^\\:tiinah\Q Bvh&X&nc^, U U posiible that r.lie 
organism, iltirin^ it* «3etoncp in the nnimal, be- 
contra iminiinixrvl ngvuiHt ^^^*- nf^tion of the nRfflrt- 
tinin juftt a* the animal betwrnes immunuod 
o^inet the toxic aetior of bacteria. Thin condi- 
tion in Iho miercM>rg3tni«ms wotilii tb*n be r«j>ro- 
*«n1ed by n j^real c<xc«fi8 cf figglulinogvnic rtv^p- 
loTs, ao tbat fl much greater nmount of ncijlutjniii 
ivoiild he rtT[mrc(i to enutc clumpiniT- It n read- 
ily iwri how llie wse of an inagpbitinablp strain of 
the tjkphoiii bacillus would affect «cnim din^osisH 
We arc to eonfiidcr that in the pbcaonjenon of 
a^glutin alien a reaetion of a cheniif^al or pbyeieo- 
cheniira! iiniure (nlte* plitrc brtwcnn thn n^ltitinln 
of th« ACTum antl the ngglulmo^fea of the micro- 
OTganisnu, tbo actual chLmping following a^ a 
consHjiienec of this reapiion. It in not a "vital" 
reaction, for dead bacterifi mnv be ag:ghitinated. 



Tkaoricft of agglutination Imvie td do, not with 
Hie «xist£Dce cf agclutinin mid aggluUuogeu, but 
rttbtr with the BAturfr of tlic reaction between tha 
two, and the iDfluencee uliich brjDg aboiU die 
dumping nftcr the rudioa liw occurred. Tbc 
oT^nftl theory of Omber enppoeed that the Aerum 
flo afTe<.*l*»<] ihe baoi^rla Uiat lb*v be^arim stioky; 
cooMqucntl)-. M they came in contact, thcj wcn^ 
•0 to tay, gln^ toi^etber. Dineur thought changet 
occurnfi] in \ht. fln^lTa* at fbe orjrnni.vmis ft Ibfory 
which ia unlccablc because iatne bactrna are og- 
glutlnab^c uhieli do not pocuo^g flapellji!, Em- 
mrrirh Jinii T/htw r^frr n^gliitinulioii tk> tln^ ai^tjou 
of an emtynio which ie produoM by tbo boctmnm 
ilself, a Ihoory vrhhU is cot (^iien 5»>neral flrudonce, 
Bordet excludes ti^c Tltalitv oi motiHty of the or- 
^nUmfl as factors, and believes that the proceat ia 
prirr-ly a pbi-aionl nne, bccnnsc of tHi» fict that 
«omfl known chemical substancee mav W made to 
prccjpHate or to agglutinate certain other (rnh- 
danon (prpripitaHnn nf (Yi'loids by ealts) ; the 
Qteory prwupposee come change in tTic molecular 
attraetton botwwm the nnierohn^ anti ths aurround- 
in;r floid. 

Otfccr theoncrt have to do with tie question of 
procipitation. An previously fitab>d, when tbo Vd- 
ij%U% of culturca of certain organi^ma arc mixed 
with their eorr«9pondtng Immune aernma, prcdpi- 
tatn occur in the mixtunyi. It wn* mnitioned 
that fhe aiibrtanee in the Jiltratc which Ukea part 
In the precipitation may rcprocot, in part, tho ag* 
frlnticable tubstanco which haa been excreted by 
the baeteria. Nieolle auppofea that the a^lutin- 
able mbriaiicr iv^itW iri thr ottprnal layer of t)io 
bacteria and that when the aemm la added a coaf- 


tsyECTios i\i* tUMVSiry. 

nUlion mvrant in Uie enirrJi>|m, n^nilrring <yiRlp4^ 
ceDce intli the enTclopes of otber indlnduaU po^ 
(iblc- Th« theory «f PtlUuf thot the aggltiUQ&blo 
cubftUnn find* fu way to the surfaco of lh« b40* 
tciuim And ia preclpitAW by ib union irith ag- 
gluUiMii ia Aornewhat nmilur. The «h£?lJ of t!io ge>- 
8g;ilaW substAD<!« flcooiinlc for the aticky charao 
tcr irhirlt tlie rnvrlopff arijuirr-j, ncconlmic to the 
Ihwry of Gmbcr, PaUauf dtM observatioaa 
n^hich Ictn4 to ahow thftt eome Gubatflnc;^ actunlly 
LM fJttmilHl fn>m the micio-orgniiisms during ug- 
glutmatioo, and that in properly ftt«ised sped- 
mcn^ it ciui be seen as a precipitate surrouuding 
and betwe^i adjacont orgnnisms. 

The multiplicitj' of tboorics Icftds one Lo suspect 
that tJie true nature of tiie procesft Tcmiiinp objviiro. 
Th« pbyicnl mtiirw of the resrtion if strongly 
tuppurtefl by tbr fact* Ibnt brtftrrJa niny n!so be 
A^lutinated and precipituttxl bv well-known chcm- 
Jcfll dubetancea, sueti ae I^ydroclilohc acid, and by 
vapionB on^anic Jind inrrgnnir rnlloids (eolloidal 
ftolutioiifi of eafiiuiii chlorid (CnCl,), zinc *n]phflte 
(ZuSo,), ferric bydroxid (Fe(OH)^), alntninum 
hydroxtd lAl(OH),), ferric chlorid (FeCi,) and 
MluminuiJi ehloiid (AICIj), Some of tbrse sub- 
stiUutH beliavu like tiie agglutinatiD^ serums in 
the poMewion cf tbc H)-calkd proKonc; i. c, th*^y 
may fail to flg^iutinate in more eonccntmtod mIu- 
tioii*, whi^n-an aflrr tlilinion, thi^ir ag^iulinating 
power bi!PoraeM nmnlff^t [liydrotbloric acid and the 
fltopbyloGOecn^ nccordia; to Buxlon and Itohe). 
sun furtlior indirect ex'id«nee of tliis natiin} of 
tb^ leRDtioti is found in tbe obaeiration, mad? ^nt 
by Ndfser and Fricdbergcr. that two coMoida which 




liear opposite electrical charges result in sedirtienta- 
tion ^vhen they are mixed in suitable proportions. 
EoBin and Bismarck brown^ mastic and colloidal 
ferric hydroxid (Fe(OH),), colloidal silicic acid 
and colloidal ferric hydroxid are mixtures which 
behave in this way. Here also the inhibiting 
"prozone*' is obtained in concentrated solutions. 

An analogy appears to exist between bacteria 
which have absorbed agglutinin and certain colloids 
in that both may be agglutinated by the ndditjon 
of suitable electrolytea. This phase of the agglu- 
tination of bacteria was referred to previously. In 
a like manner "agglutinin- bacteria" and the col- 
loids mentioned may alike be precipitated bv 
various salts (electrolytes), such as the chlorids of 
sodium^ calcium and potassium, and many others." 

1. Bititon and Rnbc: Jour. Med. Reseorcb. inon, ie, 113 

rAPTER xr: 



ltc<;aQfie Df their Aci«iitillc importance uid c«f- 
tain practical feature*, Ihe ii^runi'predpttina 

«houId rcceirf ecmetinng more than the mcidcntal 
mcDlion which baa haen ^vi^q ttiooi under agglu- 
tiimtiiiTE nud In other cliapE era. 

In 1837 Kraus diecovered that bouiUoa culturw 
of xhQ orgOQJama of t^'photd, dtoTcm and plai^uo, 
rnsin vfh\ch tTic luifkTia had brpn rmror^ by fll- 
tralion, wouM oauae precipitates when mLced with 
thoir r*ap(Wtive snttEenima, The njactioii is ape- 
dflr. As tilsiti^l Inter. bowBver. thifl tpocifidty 
holds only when those c|uarititntive relationships 
ftr<* ol«orvcd whkh were f^uml no OMpntial for the 
a^'yluUuntifju list. The precipitins of Kratis are 
the bacterial precipitins. He propowd their use 
for the identlficati<:>n of micro-organisms, Tf, for 
mnnjplc, «nr- hiis in l»uul a cuUnre whidi he sne* 
pocta to be that of tho typhoid Iftcillua. it may be 
grown In a liquid me^uio, the cells remoTed by 
filtration, and the filtrate mixed with n Icaevm 
artib'phoid eemm : jf a precipiUte ocnirs n^hen 
tJi(? ^erum is STirTicifntly dilulwl, (he rpjidion imlU 
crttcs that Ihc organium in question is the typhoid 
bDOlIliifl- Inaamuoh na precipitins are formed dut- 
inRth^'CT^iirnff of snmp irfn-tioHS it maybe piKfliblf" 
to use thoin in clinical iiasTTOsis. for (ither 
hncti^rinl or cUiiical djupioeia flic rt^lulination 
twt ia mow readily pcrrf)rm«-t and interpTctal. 

I'lmvif I'll jus;. 

riijtoprccipitins are produced by iramiinizA' 
tion V)th albaminoua eubtttftiice« of plant orlgiu, 
u ridiL ftnd albumin from griiinK. nncl thi?ir nction 
18 epecifio fur tW huuiultf^'uus suLuUDce. 

ZoiipruapiEinfl trc oltmntd by immunui:iff with 
sniirsl albiimim. Through the work of Waawf- 
maun and Oilenhuth, of Kuttall, find otiieiv, it 
h» bocn dcmoriElrfitod 04 a gcnornl Inw that im- 
miinizdlion wKh an albtunin fron ubftUo^vcT 
tiource ci^cfi rine lo the formaticn of ft prccipiltD 
which maiufwta ite action only a^inet tho par- 
ticular AlbudiiD ii^il fnr iVie irnmtiiiivntion. Hence. 
ijie nlbumui of a pnrtimtlnr wmm, in jw>me un- 
known r»p«Gt, ia dif!«rGrLt from that of all others; 
it b KprdjiJ l» Ihi? nfiMtrji, 

IiRmunixation with milk CAUM:a the formation 
of a precipitin which Ihrova down the caB^in of 
Ihc milk iiw'l for injrrlion, bnt iiiit that of milk 
from another flppciea. The milk of the goal may 
b« diffcTCDtial«(1 from tliPt of the cow by tho tiM 
of the lactose rum. 

Ukoviee. after th* injection of c^f: white a 
pmipitin is formed which la fpociflr foi the type 

Tbr« fubatnncca aro opon to atudy jn the pre- 
ripiratinn reaction. Flral, the flxild or Biibatance 
which i« ti»c<i for immunisation ; it boan ihc name 
of pTCdpitoj!i>n, i. c, the pnwipjtiii-proditciiig «uV 
Flnnre. Secottd, (he specrlflc confllitnent of the 
prvcipitatinjf acmn, i- e, the prfdprtin. Third, 
the precipitate, which is a con^oquonce of the reao' 
liuD iN-Lwcni pnic-]piti]^;rn nn'l pnripif-in. Wp nm 
nUe to i«oo^iit in this instanoe tito actuaJ ood- 
prodiLet of a reactlonj a oomdition which ia not ao 
««alj rr*li2P"3 in other "imnuiniiy reaction*,'' II 

I In* abd 

II Inn. 




lXt£CTWX AyO ^JfJIi/iV/ri". 

ft* r nifi t litu « f 

Una ■■4| 1«M. 

is (rut, af courao, that little hots boon l«trued oort- 
caming the nnturc cf tbi^^d^proi^uct; ita diecnU- 
trv is OS fJark oa that of tlie protelija in genera]. 

Aa atatv^ ill the chapter on ''Nnhirnl ImmtJii* 
itv/' nnrmai Bpnirmi m-r'nairinntly hnve the power 
to cause precipitates in otW ffernm*. Precipitins 
for egg nibumin nnd ^rKit Aenim h^ivo b^n found 
in ENtrnots of or^aiiFi, nttliougfi al: t\\& ftame time 
they were tilj«ent from the «rnim of the ftnimal. 
In tliifi CRuc* tho ai^livft boi3ip« met in th? cells a« 
''sesfiile receploni.'' fiml Ij Uie pmc'ea of i^jilraciUon 
they arc brouftht into solution. Durinir immuniza* 
(ion Ihwo «am» rdceptora an? fltimulatwl to onar- 
[iroiluction and «re throve inti) the circulation a."* 
free precipitin rutwptom. 

The powrr of forming prncipilirs jnav he wiflcly 
distributed among the orfaos. This fuB(?tion haa 
been aa«if;(n«d to ttio leucocytos (Kraiis nn^ Xjtva- 
Htti. Koll)r fttJil in one fa*e they were formeil 
loeally in tJic fintorior chnmber of the eye (t< 
Dungvrn, Homer). 

Por the £rtiOdal produclion of preeipitiiia the 
J^rcripi[lnoJ;Pno^l^ rtuiti in«y bu injected into the 
vrinn, porltonrnl cflvJty or thp stih<-ntftrieouft tiwiw". 
Within from fi>ur ami a 1m!f to five linxi iW pre- 
cipitin hflji boon formed h^ inch nn **xtent that it 
mny he ilemonHfrnted in the semm of the fui- 
mnnixefl animal, 

Ab in the f*n£C» of agglutinin formation, not all 
nnfmaU have equally the power of forming % pn^ 
ripitin for a given albumin^ This point, as re- 
late to aonim predpitina. is of partienlar impor- 
iniitv^ ami involves a fiiclor whiHi i* rif nn (rm*r- 
i)ucnce in bacterial agglutinins. In the fi»t 
plaoo, an animnl tHII rot form a precipitin which 



ii teiii^c nt^ninH iU own i;cntin» i. u.^ V bloecHng 
ui oiiimsl 4ini] rdiijtcting llie ^cnim a fip<'clfic pi-e- 
cipilin irt not formal. If Tormcil it would he an 
autoprocipltiiif imd, ]i« ft ru\tj, nmmAU do not form 
aiUibocIied for lliinr owh Uxhuc i^utiHliluciit», 
Afiakn, iimmolfl nro Ica* likely lt> form nntihodica 
for 1h« tUflue ron^titucnU of other mon^bers of the 
Mn^e ^gin^vsL ihnn for Lliutn of tfUirr H]K?rL(^; tlii-»i\ 
nhcn formk?(i. are cnllcd uo ontibodiot- Sohuto 
imimmiiied tliii1v-t«y> rftljbit^ wkb iernm hnm Jho 
rabbit Anil otitnaiwl an isc-prccipitin fnjm cinly two 
of the nuinbcir. In th« tliinl pk^P, nnminU do not 
readilj fonn arll-bodie* for tJie ti^wie ronffituerts 
of other animnlA vrhuh xooIo^rirnEly nr bi^ioirkittly 
nre (?Io««ly ivhtcd. TTniniiniianon of ihe piiiipft- 
pi^ vritJi tbtf »-rmii tff tlii* t^Lbil, a fg^i-un w'tlh 
tbnt of a dLickcit. or a monkey nith human fCTiim, 
*rf» prooMnroe which innnlly do not vipid prt^ripi- 

Cl>emi*iilh". little it known ol prr^oipitinp. Thfty 
nro thrnwn down hy amTnoninm milphate In c-i^d- 
jtindfon witTj tbr-euplobdiu fmctio:iof »cnim, nnJ 
nro destroyed by thoM? substftncca which niter d- 
bumiDous bodjfs, OA acidii. alhali^^ p^pr^Io and 
tTTpain. That bacterial (.recipitjiu are n»t iden- 
tical with Ngglutlninfl fur the anm? bact«m is 
■hovii by ihtf TolWing fai-l?: I[tiii]t]fiixali»i] witb 
ecrtoitt bacteria nu-iv produce njc^lntinin but no 
pncipitln*. Precipitins d^elop moro flovly than 
H^^lutinini:. A« n nilr prvcipitiDS are inacUiate4 
at lower lempi^ratarc* than A;:s^utininn. 

When aenim ia boated to from fiO* to 60* C. ita 
ability to cauae a pr«cipitjile in thr homolognxia 
pnecipitoirm J5 ikntroycd, aJtfacii^h it may be dem- 
onstrate that th? po\^«r to rombfno irilh ih^ )nt* 


ifiF/^ryrmx a^d iHMUXirr. 


(cr M ttiichjui$«d. ITenrc fTecipaitiir like Aj^lu- 
tiniQ, %$ composed of tvo $T^oup«, a bindini; or 
tiipFophorous, and & ferm^nNfihe group in uluclt 
the active propcrtj reside; t*»e Intter is the eoag- 
TiliD of tlio moleeuU. Wboii pr^ipitin hfts lost Uk 
eoaguliD it bocomcc j>rccipitoirJ, and jib precipitoii] 
it mar UDit« wiUi precJpitog<^ iiad thereby tabi^tt 
1li« action of a frvBJi precipitin wliicli may be 
Ji4<lc(l later- Wiicn a prodpitnting scmrn has 
partly iJcgen^rated into pr*cipil;>id<, that is, when 
it i»iutij^ of n piixtuiv pf prvvipitiii uud precipj- 
loidt it is found thBi tJic latter hAvc th« greater 
anrmStv for preeipiio^«D; Iiencen in corc«ntrftte<i 
Pfllutionn of Ibc wrnnn, prtvipitoHl may be present 
ID fldficicrtt qtmDnt>' to bind all tlic ATaiUblc piyv 
clpilo^, and the ri?aotion t^ould not occur in 
ipitc of the prcceticc of active precipitin. TttU i% 
Bpokf>n of M ^icciHe inhibitiort The aetion U 
tian\ni^u% lo Ihitt of tnxotdit nnil Ag]crTuttnoJdR, and 
the phenomenon i^ mentioned again in thifl in- 
fftan^ in or<ler to emphostiBe the foot that oertAJn 
pHfiHpIp*! t>f action are romTnon ixt maity of the 
irimiine RubiAaneeft. Pntipitoidft. likrr toxoids and 
a^^hittnoiiU, «ro formed by lonp *trtnHfri;, by the 
aefion of henl Anrl 1i|rlit and by otlier injtirlous In- 

The molfeulc of preeipitin. 1Jk« that of ftgiEln- 
tiiiin, is u rm*4'p(or nf tlie *i?i-*i>[n] unvl^'r (Fi^. G). 

Tlie attempt ho* been morio to produce anlipre- 
cipittns by immnntiation vriih prwipltatinp: 
wnim^; thi* is SmmiinErHfirJT] with *ti immnni? 
ecnim. It ia reported 1liat flntibodies have been 
obtair*d for Udoe&riim, but not for haeterbil pre- 
pipilin*. niiero is h limit f^ the cycle of nrlil»ody 



PneJmtojML toav be deGced as &dv alttTiminmi); Tt«rDrt> or 
sillsUnci^ immunu^IinJL with which aviU ctiuse Uie «mi. 
formation of a epeoiflc procipiUting ecrura. In 
fld4ttion to those uicntioi^'d above, altiuminous 
ttrine, pleural exudates, ascitic fluid and Uiat frotn 
tiTdnwcle flfc prcoipito^rifi. The ia trvie of 
eoma albuminotis frjii:rrioDK of scmrnK, lu ftloliEiUu, 
llie prtcipitating aeruiti for ivliich m^y be called 
■LutiffloLiuliT). Krazi5 boHeves timt th<^ prccipitogca 
of bactena] flTtratPS is jiHfitiristpd with ftlhinniiuni* 
iiiolcciilc!^. Jacoby obtairjotl by Irypttc dipcatioD 
of ricin, a procipitogrtn which ^vt'jt no albumio 
n»ctioTi. On the other liand. certain prtvipito- 
f^jit^ Arc destroyed by prp.iin add tryptcc. a fact 
which indicates their slbnTninotja nflturn, 

Cprtiiiu pntipili)j<t'iin jire said Lo cGiiaiat of a 
thcrmolabilc ad^ a thcrmoslnbilc portion, the dif* 
ferenliatiin of which wd nwl hardly ronsidpr. 

It is of no litlJr iiitrrrit tK«t m'tt^irdtoiwii, eimi- I'mclifiiBW 
lar to prpcipttm. coraiala of Iwo irroups, throusn rr«'oii>iio«;Tti, 
one of vhich it imitra with pTT?i?ipitin» whotviwi thr 
other ha« a congnlnting fimetion. K^g albumtiit 
for exomplo, wlipn hontcil to rather htj;h tempera' 
tiirtt, loin*» iLn hhiliiy l-> pjLrtici|iato fn the pre- 
cipitation reaction, nllhoLiirh it retains its binding 
power for precipitin. In viaw of tho fact that Iho 
two mihuJani?™ ohich enter into the reat-Uoii liate 
aimilAr etructtr^fl. it is <Jiffic:»It to say which m> 
•umci the pufiait^e and which tlio acti^o r6Io, IV- 
Ifrncnitfd prcripito/r'n \n niKo en1ti>il pnvtpitoid. 
To ord-^T to dislinpiiish the t\vfi proeipjtoids ore 
nni*t «piTnk of t}ic preoipltoid of precipitoaon. and 
th^ precipitoid of precipitin, Tijc pracipitoid of 
protipitnBcr liclda ptcoipitin by immuiUEation ; 
iintro. It h all th^ mon) nnsilognui to th« torddt. 


tst£VTW}i Axo iM^uyiri. 


I pirn' I'm II lid 

llic |)r(cifiilate wliieh U cavtct] when n bacterial 
AllrsU ii miKcd with iU t{>ccinc^ onUfcrum forms 
ia from on^-faalF hour to 5ovcral boors, ildJ oppcara 
Aid H coherent wliite kvilim^Tit which in the txtuntf 
of Iwpnty-foiir bour* hn* left the ovcrlrirg fluid 
luile cl*ar. The action nf tlio precipitini; foi 
ummft i« itioro I'aptil, ami in dihor coae se<limcn< 
tafion ii }ia4tcn<?4l b>' pidcinf: Ihc nui<1« nt bwly 
icmporatuTO, As ifitimat«i) aboT^. tlie uccurren^ 
i)f Ihf- n<iulic)ri (Tf'jicMiU au iin iiibu'i c-Diidilion of 
Ihc coAgulio ^'oopa of botli snbstnnccR. A low 
coil (^cnlTAt ion of or^mnic ac4il fai'ors^ wh^retu miii< 
ctilI ncliK nnf[ nlfinlitvt Li]lii]>it, or prcvitrit prorJpi* 
tfltion; a ncutrnl roactioD is iDiiifForCDt. Tho pre- 
ciplUtc containi albumin, whi<^h, hoi*'e*^r. hu* be- 
come 90 chim^ that it it not susceptible to tho 
action of trypsin. The ivtt id coiiibiiun^ hnre in 
9otm vnv jthtit afi the point of nttOf-k fnr trypftiii, 
A ladciwrum precipitato the cawia of the corre- 
cpottdiDfE niillf. The pn^soDCC* of aolts is ttoocitLarv 
fnr ihti rE<iii-tioii of pi-iH.-jpitaUoi]. Bnlh H^lutiiiiti 
and sgglulioogen are prcaefit in the precipitnte, 
but ihciu teemt U> ba no law sov^niinjr tlic 
aujt^iitiU of «<rcli iit the conilinotior. 

The supcrnntant fluid oonlaina a rcnminiBg 
^luhk' pait of holh Ki)bfitanc*p« n» can l>« tihown by 
mWmyi frosih ptpctpitin mid vica ver$e. 

Oro\iTi precipitation is not eo pronounced aa 
group [ijir;: ;Uinfttion, vH it oxiita to a eorlain da- 
irroc aind ia of Ihc ii(mcn4 pmcUcal impcrtnnce in 
attempting to diflCTPnliati.* senima by tht? precipi- 
lafion method. Although bactorial pTvcipitinn btv 
hijhl.v specific, it is iinpoitant to observe Uie prin- 
ciple of Hcrun diktioD which voa ^mphaaized 
under a^UitinaHon. in <it*1ot to obtain tho advni- 




th«y do Dot iriicrfcre with thv chu-f prceipitin. 

'riiat feiitiire of the prLVJpIUIioD rPActJon whidi r«n*ii»i*- 
haa tK« ii:09l; piiicticnl beann^^ has to (lo with it« rrT-c<itiii»< 
modic^toj^al u^i* in thi^ c!ot«<?tt^n of hiiirtAn blond. 
PW Uiift [fuqujH* it liiiB tiupiiWileJ the ej*cilic 
hemolytic fcniin«, which arc to be referred to later. 
In Th» <N3ura6 of inr^tigiLtioriB it wite found thaf 
even tlir KTimlWl. dritftl hlood slain, dlthougli 
monUifi old. noiild cauec the formation of a «cdi* 
meet vrhcD tiiU&d irith Kn homologona precEplUt- 
in>! NTum, U TV^Him^l for c^rrtnin import>uit de< 
tiki[8 to he worked out in order to render tho l«t 
tufHcipnllv rdinhlo for fon.'UBit wurk. The upr- 
dlkit;r of Uie reaction appoELied to be threati^ncd 
aomewhat when it won Ivarued that the eenim of 
mottkovs iindrr^t'ii pi-PcipitrtHnn whi*n (n-jiipil hy 
«ti immune terum wliidi is Apeclilc (or human 
tfcrum. Thi« ii^ nj^iiin, ^^ronp precipitation. Ail- 
ventitJoua preciphalion is, in f»ft. «i widenprp(ul 
Hint some have fett juatificcl m ApcakiDg of a mam- 
mnliari erriitn rcneliori, Honoo, in OTt\tT to inimrc 
^pK'ifJcity. it has become Deoe^arv to ii^ ijrwiw 
CjLiantitAtiro mcUioilA in dilfrrf^tiatinj; hlootht or 
«ipnun9 by thU m&lhod. The immune wmm which 
U TiBral in ihi? it*** must En- diluEM lo wme lytti^nl 
in order to Himinotc occiH^tnl prcripitinp; but 
(ven a more Important prec-antion fa ihe volume- 
ric mpaxun^nicnt of (he prrcipitntr whlrh i« 
formci Tbc tedmic of Scl^nr may be eit^. T*«t 
ttibti are tornado Ihnt tliolowermmt jiortbn <*on- 
autt of ft iJaduaCed capirary lube. One e.c. of the 
fluid itt fce teft«4 in pia^^M in one of thece tnbG». to 
vhich is thc-n addgd 0,2 c.c, of tho prcoifiitating 
0cram. The miULte h Itept at ljw3y tempcraturt 


ixfEcrmx Ah'O tMMUfarr. 

until the roacUon k complcU, and the Aedimeat xt 
tlMi Utrown into Iho npillan' portion of Ui« tube 
by ofintrirug«tioQ for a «Ut«d period of tiioe 
(tmmty muiutc»>. The volnmc of Ui« Mdimcnt 
miiv bo read faj Vw aoale. NutUll ftllovs the Mdi- 
immtiUion to occur Tuitiirallv, with the Lulioi In an 
ttprif ht poflitioft. Otii^ acromfl CAtHralty mvft 
b« luod t# cooitrolj- If the 'Smknown'' blood U 
»nfLj>fl¥trd nf b«ing litimui, « controi ttibn mn>4 1« 
prcpftrrd in which a mniiJar uoount of knovn bu- 
man wniin w ^nbtnittttl 1o tlic fonw Utt. If the 
tv(» liibn yielcl simiUr «r)ioimb of prrcipit«t« 
w]^n ttiCT »rc trt«1«d wiUi 0.8 c.c. of a prwipi- 
tin yihkh in fpoctfic for hnn*-AD vvrum, tHo identitj 
of tiie "Bfikt^owii" blood AM tbat of ruao a olab- 
Ifebvd. To obtain the specilie prodpitio it is cvs- 
tomary to immittiw rabhiu v-Itb buTnitn onmnt for 
aevenl wf*!;*, 
M*Biti*«iUB Another practtctl f^atnro of th<^ preeipitntiop 
ivd b«a U> do with tfa» difTcTvntiation of mMtd. A 
pncipitosietioui lulwhuicv Tftich ift diandcrUtk 
for th« nainnail may b« ^xtrftd^ or pr««i«d from 
the flfttb. and vill }ielil a precipitate vb^n it ia 
miirrd vii!i » prreipttm of bomolo^oiu natnre- 
Tbic ift of particular itit««st im tbow eoiotHct is 
wh!cli the moat of tbn borsi* in put nn the mnrlxt 
M A imbatituto for that of bc^f. 

(For 1h« r*lfltir>n of preeipitiiu to anaphvlaxti 
M^ chiijikr or nnaphyljiiM-^ 

fn n«w of (be fact tliAt th« protoplasm of the 
body and the aTbnTftinonc cooKtitnmits of wnim 
Usrea cloe^ Tr^Intior^bip to. or really sk, collojds. 
mwdinUor* ba?o Hudied oortaia rcootiom irhich 
ocmr amnajT tbr knnvm colUidf with tbi> wp<*rtt- 
lion thai the r^artions of protoplasm and Ibose of 

»t Mhh. 

r*ltnM- And 
or IwtiinaMT. 



»emfUA trouUI receive «onie eluoidftLioii. Xot mudi 
adrttiiCiMtictit con Uc mode, however, untit the prop- 
«rtM« of colloiflft iLT« more thoroughly und^ratood. 
SubiUac&i nvliiL'!! \!p iulu miIuIiju were cla«ii"* 
R«i br the i"Jnjcli=*h pUynioiiL Grahnm, n» rmtol- 
louls and colloids. Cmtalbids Indude many In- 
onciuik NLhd. usually tlicy fnrni clcur H^ltititiait 
in tt'aler and cic^rt osmotic prce^furo, euppoect^ly 
betTiiise of the »inaU si^t* jf tht-jr moIiHrult-!*. They 
diiruH irith some TApiilitY and nan}- fire conduo 
ton t\i electricity. Organic oolloiclfi <iompnao encli 
NLitbiGtmirL'^ wt ulbumin, Klnrc-h, ^cxtrin^ liiruiio. 
gelatin anrl macv ^ma- By prtiiKT Irealtncnt of 
f*L*rtnin metal* and their wiltd, inoipiuriK* colloiJ* 
may ho prepared ; for psnmpln, fiTrir hydmtiil nnd 
th»* sulphida of antimony and uwcaic. When col- 
loidi lire (liKuoh'Lv! in wntor thA lolutiomK arc often 
more or Ictw opaque, aiMl are soiiietlmcp opaU'ecent 
because ihvt pnrik[e« cr molccnlcsi crc of tiucH ftize 
tlint they polariso light. Th«y ^xist in watarcithor 
aa a «ulu(iofi uf rtit)leL-ri]e» of great ^ize or aa a aue^ 
(H-nnifin of eontridcrnblf particle or a^rcgates of 
mole^n!*»*. In srime instanciw the pnrtif^lpe are ks 
1ar£V that thvy may 1)l^ «cim by a ma^nificatiou of 
1.000 diamM<>riti «rhilo in othcr« no dofrfee of ma^i- 
iiifSrslion rfnd^rs tliom vifibi? with tlip ordinary 
mtrro!»rt>pc. iV ^J"J ^*™^ ^f' *'^'' recently derised 
ultrani}croeco)>«, howe\xr. the finoet partioTpja in 
aorne colloidal aolntioiw mfly be diwrrnofl. T^il- 
loifla] tab«tanec«, audi oa albumin, ditTnac rery 
alawly and e.vcrt little or no OTmoti^ prwsufe. fup- 
prunlly Itrf-jiuif of thr Ur^** M^i' of thii' pnrli^^le*. 
They do tot condnrt el^ictricity. bnt thfi particles 
^omaelTfn xittX to the eleetrio current by alter*- 
tioTjn in tbr dircvticm of Iheir motinm (\. e.. towani 




iSFBGTtOS AXD JifJftJ,V/n'- 

•r t-«iiAii|a br 

the pofiitirfi or tbe [M<gaUvc pob)» And, moroovtff, 
carr>- dcctric chirgcv th«ni«£lvies, 

lliv fcatiir«e of colloide which hrin£ them into 
relation with thv Aubjocrt in hand arc th«ir coagu- 
Ub!c ntturo in ocrtftiu iuAtBifcw uud tbtr fAct fhnt 
Ihvir pirlidcs mov be akjc^^^i tilled or prccipj- 
tutttd hr Ili4r aiMitfon of minnt# Amoiinta of soItA 
(dectrolytfs] . In tbU counectioii on<< nkturtlly 
TisCKtn to the ottservatioD of Bordot, wl^ich was 
mcDlion^ in iVr pr^edJng chapter, c»Dcerniiig 
the lAiffgluliDaliitity of inicro-orjfiujiinK so loBg 
Aft salt 18 withhold from tho eolution. Tbta final- 
ogi^' noiiM flug^eU tliAt the bacterid after their 
tinion witit AjrJZ^tJtittio tn*y conduct themMlvce aa 
n>1loid«l pftrtide^ Id th9 precipitfttion of c<^loid« 
bv »aItA it hoa b««u Higgwlpd UiHt tht> ultx so 
niter the cltclric condition of the oolloldal porti- 
rk« that thdr Gurfa^e t^naion is Jccreaaod, and u 
a rank of IMn HianK<^ iici^))bi>nng particles 
conloeco in such <iuontitieB ne 1o produce ft mil^lc 

Ndafi^ acd Frictlberfcr hnt^- ftuiUed certain 
oaLloicjp, havirif! in mind the similarity of th<^r bC'* 
harior to ui^mm rvactionF. Tlifv founrl, for ^Kftiii- 
pie, that tnro of our common dyas nhich arc col* 
loitM and bi^nr opposite chiirjic* of doctricity (coain 
and BiHrnarrt brown), give rise (o n pmipltflte 
when the iw'O nrc mix'^'l, FiirlhffTmor^. the *po* 
nfi^ inhibition which may be obtained in tho reac- 
tion with «emm pr«*ipitiHs (see uboire) conW alito 
be realised with tbe ec«iii end Dimnarck brown. 

The Of^Jvtti nation of baelcria and of red blood 
Mitt mflv nhn be flfrdmpHnhpd with (\ilIoifU- 
tAadsteiiier aEglnlinated cryfi-rocyles witJi col- 
lofdnt fiilioii? fioid. 


Antibacterial, WCcrloidd and Isact^FtolTtlc arc 
UtreeUrmi whicli an: tscti in a ratlicr loontt, inter. 
cha&j;o«l>!« vay* flUlioiifih iticy oro not *tnclly 
Bynnnymous, A bflrtpricidnl wrrum in one which i* 
able to kill bftcteria, a« tlie t«rm impHes ; if at the 
samo time it dtn^^lvot tho orgonintng it i* bactGrio- 

<lo kill boctcrifl withmit disnoWinjc tbcm^ while 
othere, &fl Qntieliotcran hav« the diasoW^nj; power, 
th«! (ttfttinctinii liflii ji ciTtnin sti^iiflcnnrc. In nilhrr 
caae tbe Mtuiu i^ of courti?, unEiU^lttial. For 
lick of a more conciw Kn^li^h term, bacUnoli-nu 
ift UAcd to de«ig7iHte the prooeu io whif^h bucterla, 
witli or wllhoat folutioii. are kUlc^ by »i^uiiii«. 
B«rT«rloh<Fin infers 1o tho tiibfrtancea in ktuiu 
U'liirh m'C^fiiipUth thii ncltfiTi. The mt^uiu of il^ 
tormiiiing tJic bactaicidal power of a serum aw 
iadlciti>d on pA;^ 25-1. True bacti>rio]yiii b b««l 
flbaerv^ with thr or^nrtltm nf rholrm nnd !l« 
IBtittnun aa described Ijit>:r under the title of th< 
Woiffcr cxpcrimcot. 

Bartmi>ly«?nR itr*^ fiir more compleic than anti- 
loxinf, Ajci^tiitininft and prrcipttins. One maybtMt 
appr^iBtc thflir w.iturd ns nnder*tooi) at pMAent 
by Inu-'iii^ t^iinr di?vHci|irnmt. frtmi thi' rrUtiTrly 
rimple alojiDs of Buclmer. 

FotlowiofC tiM inTtttigationi of Fodor, Bohrinfj 
and others, wfiich riiowed tiiat nonnnl blood ciav 

■Kill Rjirtrrl* 




Til* Phrnikm- 
man 'It 
r fritter. 

kill bactorifi in the tnt-liibc, «iid after a^ditionftl 
fftctj were obtained hy Nutlalt^ Btiohner d^mon- 
f^mltnl Ihst it is doi ntfi^vfoty iy ii^r tJie full blood 
ill ordtT lo cbUin the boctericiilal action, but that 
li^rum nlono bfl« o fiimilar effect Hq spoke of the 
urilibadEml ftaWanravi mllrdivrly f^i^ nkxfnfl 
(«abstanccB which vaH olT), taking iht rciMii- 
abk Tictf thfit nntaral immunity to htidortA do- 
p^daon their preacnce in the body. Tho increued 
bartcridfla! power of the Mram which devolopi 
durinjE iminunttatioi: or itifoction with certain 
micTO-OTgjinisma go^ hand in hftnd witb the in- 
crcMCfl rcsis(nt)f« at il^c indiriduAl s^&ijitt iht 
infw^tion* 'llic al*^\iiLi have undergone & apcdfie 
incTMM; tliey afo now immune alQxiui or, as vt 
MV tv-day. hnmuue W'teriolysiti^, ninl it i* *np- 
pMed that acquired immunity, in tl«* instiDces, 
dopoads on their new formtitioiL 

Alofin* Vfen wiy ieosriti^-e suhrtacfcs ; they liia- 
aj>peareJ sjwtitaiKoujly from aerums iii n few 
daya, were dtstroycd by a nthcr low t^cp-cc of 
heat (55* Or by acids and ollctUa, and were 
active only In llie presenra at certain salts, espe- 
cially eodiurn cblon'f^. A «tnkin^ feature of 
alexins, a« di|;tin^[^bcd from cbemicii] hactcri- 
cide*, wflj their marked wlectiTe action on boo- 
icm. Tlie alexins of animal A might destroy one 
micro-organ iom readily and aSoct aaotJ:cT httle or 
none at all^ whereas tbo« of atkimal B might have 

Work wliich waa instituted by PfcUTrr and de- 
rolopc*! furlbcT ly other* led Iho way to a mora 
correct im^lerstaiiding of tba nature of alcxfno. 
PfrifTcr stndii:i) tic bactericidal action of seruma 



in tli9 Wlj of tliL* Ihiiig liuiinul^ i. i^.. iii tlie peri- 
toneal c&Tity. Hifl most t\&mt rctulld were fib- 
taincd with the orgoiiinn of cLolera. A gulncA- 
pi^ i» imniiniL^'pd A^inat iJtii^ iiiicrci'm-gzitii.-'in li; 
injeciioiiB of i\\t kilM or living; bockcifl, Wc Ihitc 
«lroiid^ learned of this procesB oe that of active 
AntJ1>BctcriAl imiituJiizBtiQn. WJien tlm animal is 
vtU imranniaed tho cxponmcnt is bogun by the 
intraperitoDCiLt injeL-litm of u quantity of culture 
which would be fatal to he uoimuiiLni^ci Aiiimal. 
At intervals dunri^' thf* «ext twecty or thirty min- 
DtOB ffmsU amoiiniH ftf jmntorii*nl f!uul im^. rc^muvfK! 
for .nitCToticcipit: L^xmctjnution by ntcarA of iino 
pipctioi which ha?>T bc^cn cirnu'a out in the Hame. 
The flbdominal wall la punctnrpil with the pi- 
pdtc tiirougli an inciaion m ih^ ebiii and the 
fluid 6owft into tha tube by capillary attraotioii. 
A portion of the fluitl is oxamtTind 114^ a h/iTi^in^- 
drop or dncd on a cover-f^law, futod in thcr tlatno 
and fitained with a dilute eolation of carboN 
fw^bMti. Til l-he hui^liig-drup it U fii*t noticed 
that t^c organiBm* have Jost their motility; the 
comtua-tbafwd and S-fihaped form^ soon bocom^ 
«pJkcri<9l aiid iit fir^l appt^r sHulltn niid ilean 
irhertM in later propnrolioUK they ^^ndunlly de- 
emio in si^o and shnw a very rapid rihrsting 
movement, tlie jio-tvLlKvl BrotfuJan movemenU 
whicli ifl purely phyiai^al in rntiire. In the courac 
of from twenty to tbii-ty niiniilea the organisma 
TiAT^ hcrm completely di^folvrd. I'hcM nhjuirca 
iTjav hi" f'>llownd in Iho stained 'pocimons, in whirh 
ilir Hlt»'»'i] ci'lU pvi<ntmil1y ^ippmr its fiii"^ ii'd 

Si )f4?lcUiii):olT. H'^rdct and o1h*T» have «howii 
tb'' ■am'* mult mav hr obUini'd without the intcr- 

mmi 111 Vlir*.i 


tstmrios A.yn mavMrr. 

<laA Af an in* 

voDtioQ of Ujc auibiaI body, by luiiJDg perfMtlj 
froeh tatJcholcTA «erum witU tho ribnoe and 
mi>iiiitjiig a« a liangiog-drop prcparatioL. TTic 
tUde maat be kept At the tempcrAtur<; of tbc bodr 
by En^ne cf n wann «ta^. Tb« reactioo* how- 
ever, U fnr ItvK tfigorouti Utau wlit^ it Uke* place 
ja the peritonei CATity and the aolutioo of tfa« 
colU may not bft complete. Xo bacterium 1b bo 
('omplrlrly i^liittDltvd umirr Lhiw? rociOiiionK jm thi? 
vibrio of cho[«T«, dtiion^ the lyplioii bacillua and 
umiUr orgaiucmt undfrrgo tcma cbangct iu Ibeir 

Tho «p*rimi^iit of Pfoiffcr mar nlfo be *iMi- 
rlnrrCiMl in tb« nMomirRl r^vity of n noD-Ttnmune 
guiaea-pig liy iiijwUtig uxittcTiolent *erum in con- 
junction with the culttiK (pa^ivc untihflcteritl 
imTOTiTilzatioQ). Thfs is the clnulc Pfoiff«r ^iperi* 
mcnt. Tbi? iiriEiitinr larTuni iJioiilil Iw* i>f such 
etrcDgth iLnd should bo jEivcn in euch qiiflntity that 
|}ie animil it vn*^ in i|iito of the ten fnUt do^es 
of cuUijrc wlkicb the typic&l experiment dem&nds. 
KxperimontR brou/jht to lij*ht a conditirm wluch 
ivomftl pflmiloTio; nn ahl intmuno (flrum wbtc-h 
bad 1t»t iU b^cUrrlcidal power aa maiiif««te^ in 
Wfro, or one in whidi thd Alexins bud bocn, do- 
fifpnyel hy e l^mperatiine of fiO* C sh<yw^ it* 
oriKinil prolcctivf power iu thr &nimii] experi- 
ment. F^rtb«ritiOT«. when an inactive immnno 
m^nmi was iitjwloil info th« iibilom^nnl oarily. al' 
lovpd to rcrmain for a time and then withdrawn, 
ita baotpficidnl T»<>w^r for Mperim^ts «n ififro waa 
fmind tn br rp-eatahlislied. On thp hnj=ifi of tb^s* 
f«ctB, PfeiffcT condttded that ^t specific aub- 
ftiiBCC is prsemt in t^« immune scmm in an ina<^' 
iSw form, and ihtt it beoomw artite a* a r*»Tilt 

rF£tFl^^lC'S rUKSO^iESOX. 


of cookct with living tiaeue cells, aupposelly the 
akdoithdial Cdlla of the peritonmim. According co 
this condLuiioii> on utActitc scmni couM become 
fictivo ojEALD only after its irLtrodaction into the 

It rerosined for Bordet to show, on the con- l')^^^'*j^^^l\'^. 
trary, that coatoet of the scrum nith livins cqUa 7u!h. 
it not ittfcpfi«iirj 1o leniWr it sdlve for bncttrid- 
dp] exjwrimenU in vilro. It ih sufTMiient lo add 
tn the heated inimxinc Fcrum n amnEI Amount of 
fresh tiorirtfll serum fmtn ^me nonnal aikiinnl, 
Hit <]uniLlitj' of uoiiual seruiti which is uaed doI 
bnng in itMlf bucti^ricidnL Utiil^r thofio condi* 
iiona, then, vre h»v^ Eo do wiDi two serarim whidi, 
vben combined, nre hactcriddnl. hut vrhr^ii wpn* 
rated sr« insclivo. Th« di>«triiGtioii of tlio active 
jirijpt-rij of A H^rurri b_v lu'ai or hv otIn*r mniiiif j» 
CoJlcd Jn&ctiTatian, nnd the re'e«l8bli«jimc-nt of its 
poorer bv the addition of fresh normul Ktruin in 
rtficTlivfltinr}, Thr immunp serum, whpn hrflted to 
55 to GO* C, loses somcthb" which is t'sseiitial to 
iti ictivity, atui tlii* something mny b« rt»pTiiccd 
by the normal wnmi. Tliat (lie substance h\ llio 
Dermitl ecrum i.t iflrrntirAl with tlmt ^-hich wn« dc< 
stro}'^ in th@ immune serum i« ind]ca1«d by the 
fftcl tijiit it iH df'tstrtw'il hy f!ii' jwmr rln^frcw "f 
hcfit; ft he&tcd rormal scntm vlll not rcActivate 
en immnne ftenim^ 

'Hie ronc^usinn of Ponlpt that tlip l>acl*-riculal rtrn *Hh- 
pQver of a wrum dep^ndei or the coiribined action nnnvFipiiiiii 
of two wbrtuncTfli has bpen «iihet6Qtiflted hy nuirer- 
one Savntfgetor^, Tlir?^!' nrp the HuhMtimfys whii^h 
in rwcnt vcflm hntc become familiar under the 
nftm«e of amboceptor and coicpl^rment end thdr 
vnrioQi pynortrmF (wc p. SjG). One al tliem» the 



ITCr^CriOX a K& fUMUMt V. 



imloceptor, i* 1i<4t^rf«utant tthermoftabile) , l ft, 
it lA not <Jn«troj«d at ftS" C»^ vUereaa tlw other* 
the complement, b ^ntceptiNu to hetl (thynno- 
Inbitc), bcinjT destroTcd at thnt tcmpcroturc vhkh 
killed tlip ftkxinp of Hdchnor. The term alojcm 
ifi bUII apjilitd hy mmt vfniKn io ihf. Llitfrmulnbtl^ 
ffubatancc (compIcrniicDt) , ita onjzin«l fjj|niilicfliic« 
hitring b^a modiflod. 

The npecificity which provaila «jiiong auiUtoiLnji 
mill r^gglutinlri!: :a found aUo in the actioQ of boc- 
t«nddal serumE. When an anticholera a^rum u 
injectnl into ihn prritomnl cnvify of a guinea* 
pig, protection ia not afforded A^iiut other Ttbhos 
or oilier pathogeuif? orgaiiiam». Tlje specfflcily ia 
so great thftt the rcnctinn of PfcifTer moy be njicd 
for the id(>ntLfLcat;on of bact^d. II ono has in 
Imml im imkniiwn vibrio, tbi tOiMitity or non-it^pn- 
tity 0^ the orjraniam of oholera m&y he determined 
bv InJectiDg it, Jn coujunetion with aiiticholeni 
sFTutn, iBin tbf* prrHonwi! onvitr of s nnrmal 
;:i.>mea-pi j: : if the microbe i« truuformed into 
^«nnW it k the vibrio of oHoIot'ii, otl^Twiae it U 
not. Oth<?r bnderia tnay ho identified in a similar 
manner hy the use of the proper *icruma- In apitc 
of thif high »p«ificUy. tlie pronp reaction may 
orriir f^nn w-itb hiu-h*nidrhil wn:"!^- An anti- 
tiphoid acrum, fr>r eiomple, shovi tte elrongeat 
haelcrif*Mn] power for the tj'phoid bne:llas» al' 
though it ifl at the sflme time more destructive for 
ctoKly related orjsrAniGma, nn the colon haeiUnaT 
than a normal si^mm from the sflm* i^iecio?. By 
diluting the senim TTufTiricnUy the Hrlvifntltious 
bftrlfTi^ly*inB nrr eo nearly elimirotcd that the 
^fvifdh" ftf the eeram for ita homolo^^na orjian- 
tstn bivotne* manifcfct. 



BsidLTiriiliil M>ruiTiit &n< iidL obtuiited wtUi equal 
rcadincM for fill micro-CT^tiiftma, We atc most 
fntnilinr vith tho^ \.'\\\iA\ tire yielded bv imtnimi* 
thUdti nr infivtimi wifh ihn mirrolrfw of chnlrr*, 
typlioid, plagxif, th« coIooq bflcUliu and r«ktcd bac- 
toria. Sfony oth^ bactom, m th? pixumo^occu*, 
fltrvptocoocun, lubercl^ barilliis ani] othem, ^leld 
neither Antitoxin* ttor bni^tcricMd iub>tiuicc«. Id* 
Asmtich fia recoi^ry from Kiiob inf«!tlcTifl is an «3C- 
pnWoii of nrqi^intil imtiiunity, na mntii?r how 
tomporary it mar be, it is cvidc'nt that not all C-\- 
aiDpIc* of ftp*|Lurcd immunitv con be explained on 
Um basia of Ihe iw^nim properHcfl wliiHi wp row 
recognitt^. This will be referred to apaiD in rela- 
tion to phoj^ieyloais (Char^t«r XVIIl). 

K)[|>enmj*titN of nornr impoHnnn? bnvi- fn 'to 
vith tlic ftbilitv of bacterid to abarrb Hit homolo- 
gous bactcricidat subsUnci? from a aerum when the 
twt> aro miiifd in tMt-t:iib<>e Hcnr^, if natnrn! 
anlilwderial immunity [Ifptrii^K on \\w Wb-noly* 
Bin whicH ia prctfcnt in the cirrnlatioTi* n^c 
maaa of the bactoritim when inject<*d jutruvcnotmly 
«Tioi^M absorb or fix tbe bactoricidal sulstonoefl ; afl 
a oonacquenctf, ncmmt wbich is <lrawn lati?r shotilrl 
Aor & peat docrenvc in Jt» bactcncidal power for 
the or|;an[Bm which woa injcotcd. Althou;^] tc- 
mlli of thift nature have been obtafoed by a niim- 
Ut of coTnprtcril investigators, they are not with* 
(mt exception. In the ramc connection fatal infcc* 
tlona aliould be aoc<riiipa&iod by n dccrcaac of the 
natural ba^crlcf(!a! power of tlio eerum for the 
organism lovotvei]. This baa been found to be irae 
in man in rcbtaon to pla^c. and in Mtne animal 


ixrifCTroS AXO tHUlMTW 

?rriiriLft i>iK 

III a preceding chapter micro-or^-aiiiams vc» 
diridnl, lint, into tbOM which nivrpto «olab1o ti>x* 
infi. Immimization wit^ nhlcli caiiv^ l)ie forma* 
tion of onlitnxins nnd, «c<'oiid, tbcw which do not 
ftMTOlC Guch loxms and for v^hloh no miLmpuia- 
linn« known lit ihn piviuvnt tim*' nn- Kiirt^wsfiil in 
vtimulatini; (o tlic fcrnmtion of uiUtoiiDi. TScn? 
linCB, howOTCr, COQ not bo drawn fiharplv. fortbere 
nro a fvw miero-org:nni«mc ^hicb, ucvordiog to 
m»iii|Ki1atiaci, vnate tlu- fonniLlian of trJIhfrr nn 
antilo.xic BOTOm or a bflctcricidal «nim. In g*n- 
<:ra\ it may tc ^td Uiat the charflr1<'r cf the Acniin 
dtfpendti dii Uir bjirUriat 4'nn«ti1i](nL whidi lit iiu'd 
for iminuni^alioD. If tlit diphlhena bacillus it- 
self, or the py(jr>'nncnft bnci!to, i* lnjcct«d, the 
tox!n having been i^aihod uway, baGtcriddal wr> 
iiin» Ar« funned, wlif'rtug if toiJna alone are Sntro- 
dtTced, nntifoxiup arc the rcsnlt. After all, it 
MCiTiA plain that thv baetcna of th« second group 
iDuai bo pjit^og^nir. becau&@ of toxic Ruhslanoea 
uliiih tbcy ainy viih Ihcm into the bod)\ In 
view of the fiict. iiower^r, (hat they do not wccrctc 
iulubk' toiini iu culture media, it U held tlut 
Ibeir toxrc firojKTlieFi ai^ inU-grally a^80(!Latcd with 
llje bactciial protoplasm; they nrc the endotoxins 
spoken of previously. 

Tlie queatioB nAtnmlly ariftoe! Tlora a bactf ri- 
ddel senam in dimolring or killing iijt Tiomologcua 
orf^anism ncntrAli?:c the endotoxin at the t^mt 
time? On tbe baela of very positive expcrimcnta 
which hflve hf*ii pprformril, I'jtjin-ifllly by T*finffiT, 
it IS ei'ident iK^tt tbe serum hn» oc sudi action. In 
the experiment of PfciffcTt one may inject into the 
abdomen a snillcierLt quantity of antlcholera scrum 

BACTSItWiOdL ifsauiiit. 


to IriH bII the OTgnitisme vrhieb hav« b««] iiitr> 
ducfid. And yet the imiinAl oiny flic with the into^i* 
tioi\ of cholera. Furthermore, if one considers t 

culture of tho cholera vibrio, which hn« bwn killed 
hy hmU iiA T<^|)n'seiiliiig io mudi cliulera iUTii), 
tnticholcra Acrum protceU against no more of it 
thui rlanc the j^atnc <]uanUty of normal noruin. It 
ia be)iuvt>il tljat nnttcholera aiiiJ similar iniiuiiite 
beruriLa ma^v wen iucnrutic ijilciication hy diasolv- 
iiL^ the bacteria and tlius liberating on excess of 

We have Ht1l« poiiiive knowM^'« ccneernlng the 
or^aa which form the bactericidal subalaneca id 
acquired immunitv. PfcifFcr and Man;, in rela- 
tlon (o cholera, ami WaHternuui^ in typlioiii, found 
lltat Uif apieea antl the hunojioietic or^ann la gen- 
eral contain the irairnnc bodies m p^at^ concm* 
Imlion thap tht.^ blood flf^rum, nmt in imTnunizatJon 
eiperimenU the hiiMiic^ m^y he rh-inuntirrateil ir 
thcftc organs at a time ivbcn the/ arc absent from 
the circulation, Tliui fact in j^cnernll^ accepted a* 
proof of tli«iT formation at thcs« points- Woaser- 
lEtann mnd others have (.TerionetTBteil (he prewncf 
of complement in the Icucrocytca, nn^ MctchntkolT 
holds Umt it lA produced od]> by «utib ctWs. (See 
origin of upch'tininfi. Clisptcr XITI.) 

The jdnnditMuntion of bnctmcidal nMnim* J*al 
prevent more of theoretical ttiim of practical in- 
terest, bocum of their limited therapeutic lue. 
Their vahi™ mn nut hn t^ptpm\^np^\ with th** «e- 
cnmcj" with which one m*?a«urr.* a unit of anti- 
loslo. One mav 'Tclivor from a pipette a definite 
<|Qinli1j of toKtii ftnd if Iho toiin hn* bven w«ll 
procrved the ^ime quantity may be ohtalaed at 





c>bktopn)BerTcK(;uLtur«of Hvipgkftctcrna eo Uisi 
Ui9 uumbu of tho orgaitijimtt and tho Tirdeum 
of Uic culture rcnuLin coitatant, nor will bro cul- 
tures maJo at different times contain tho samo 
iium[ji-r nf cdU in n givi^n volutut- Hl<[i(?<-, ntoitd- 
«rd cultures ubich arc ncccaeory for the sjrstenuttie 
valuation of sicruins arc not ea«i]_v JivatlaLLe. OdO 
niBj UM a del1iut« volume of a boutJloa culture of 
AU organidm vbich has (towq for a certain number 
of hours, but in all likelihood no tno cnhuroa 
wtiuld cuiitaiii Llia nanit* iiuinlier uf or^huixma. 
rfciffcr UBC9 the nonud loop which has bceu ificn. 
tioncd, i, e., one which will take up from a turfaco 
nf iignr t\*'o njilligrntn* nf thr* hrtrtcml miw». 'ITiq 
cullunj muat hnye grown for a definite period, 
eighteen to tvcnty-fonr hourri. T<«le having soms 
Talu« majr be mude In the lest'tube with the freah 
or coinplcmcntril urniin. Thi*. however, gives one 
only the hact«ri{!ii]3l power as M ii inanifevtdd out- 
niifc thr txKly, am] il muy not hr n i^Drirrt index of 
tho protective power of tbe serum when it is in- 
jfytcd iuto th? living; animal. Fnr the tOrt-tub* 
e\|>erinierit vArlotis dIhilioDs of the eenim ar^ 
madi* as 1 to 10, 1 to 100 nnd J fo 1,000, and a 
similar quantity of oach dilution, proporly complo- 
mi-nti-dr is mixnl wilh it ^\w^ maa* cif tJit trultur*; 
tho mixtures arc then plar?cd in the thermostat for 
a mimber of hours. At the eml of tliis: timi? plixte 
t'liltUTT* arr made from cH^'h oT thn mixture, the 
plflt<*4 put ft^idc for !went>-fouT houra. and the 
rolonifB which hftvn deTckpod firn tlipn coiintod. 
Thr qiimititv of NTEJUi rt'quirr-d lo WW wW iJie liao 
reria mav ho taken as the hnsi* for computinir ita 
l>ad<»ricidnl value. 

tcnniiMxl br tDimaL cxpcriBicnt it i> not csecntiftl 
td odO tho dcniin vhen fresh; tn ffict« the nAtWe 
rompl^iTjpnt in tlie iirmtm? «n>m may be *?i*nv 
iraHci3. or, preferably, it mtty be rfe*troycv1 hr hc*t 
If the latter pro«dnw is ftdopte^K or if an old 
epram fg iittM in wliirh tlip fomplrmCTit hw ^<^ 
gencnted, itet rcacUi^tiijn ih Rciornplidhuil tltroii^h 
the complOBiect which i& present in the body of the 
»xp«rimttnt nnimal. Thcr* are p«fl(0M5 for boIioT- 
iu[( timt n ^irrH HrlWriim n'r)iiirLr4 n pariimlttr 
ci>niplemtnl for Ita Teacti^alion. an^l that thia 
cofDpIrnii^ht iTflv b-> profVTii in eooDO nntmnU on<J 
aWnt in olTiynt; lliis will bi* ri^ftrpud lo iRuia. 

To flD<3 Ihe value of ariticholcra fieruii] Pfeiffer 
prquirctt dilutions fimilar to thoM^ mrntioncH 
ftbcve, and lo t^<! aam* qnantily of each dilution 
ftdila icn faUT dofrn of a virulent cTiUiire of th^ 
vibrio of choicrn. Thwc are injected into the 
peritoneal ca^'iliM o( pjin<?a'|>i;rtf an^T nHor i-iorinds 
of from.fnriy ti utity miniiips Imnging-drop prep- 
anitioiu are madT' frnm thi^ prritcint^l ilnii? of rarh 
imimal to determine the formatioa of tlie diarac- 
tmrticgT*niiIp*; the liighoflt dilution which caua« 
Ihb chniigi' ill the. n^lf* stHmjw vjilur i>r tH© 
«cnim< The animal inu)t at the Amc time be pre 
t'^tf'] Ajrftinjil the ten fatal do^iea of the culture. 

The vjubi^ of un aulitjphoad Rcntm may be de- 
tennineil in tlie name truy, the rciiult being judged 
by the prot«:ti'>n which ia affonled t!ie animal 
rmlher than by the formtlion rif iifrflniileB. 

Antit;iphoid. aiilipEu<*Lie. iind wnne «<hrr nmimn 
ore alio l«ated by injecHnjc the icram twenty-four 
hour* In ndvao^ of the eulturo. 


n'F^rtox AKD jjfj/tT/n\ 

II Is ncccEsarv (o kaavr the rimlencfi of a ciH- 
tiiTG with which an niktiseram Jii teat^. It b po»- 
eibk to mfliritnin some or^picinrti.* At a rntlicr con- 
stnrt vinilenc© by pc^sjig^, i. e.» inf^rtin- animaU 
witli tiiP miirnilw" nml rwultivnling iL fmm \)\r 
imnt^^, With othc^ra* abundant controls must be 
made at tho timu the Berun U l*sled in ordtr lo 
know nt HibI niomput tfic precise vinilprco of fie 
culture. In al! probability it rtquircs more ncniin 
to protect agninat vary dnitont culturvfi than 
t^nat those of leaa viruleuca 

Va1u0 II tf 

f^vhn1« at 
VlpiiKilf iiir 

i:i|»i-f I iiiv nr^ 

n. nKUOLYwis'ft, 

Thctimplicity of hemolytic c\pcnment«iuidthc 
rapidity vith nhich they may b« porformed and 
(f?nniTmtiil luivi- n-mlcri'd Jienmly^lc 8(?rnins par- 
ticularly nscfiiL in the studv of amboceptor* and of 
con^plemcTita, for we 8to to understand that aiich 
wfumn wrc to\ic to coihrotryteH only liecni;pe nf 
the amboceptors and complcmcnta whkh they con- 
tain. The most important tac^U which hnve been 
Irnrrci concerning tiic action of hemolytic Mrumx 
liave been found to hold tnie for baclcTicidal 
ni'TurTi* nH w*>ll; hcneo it is an indifferent matU-r 
if principle? which arc common to both arc illuft- 
trnted by frequent roforeocca to Ecrum-bemolyain*, 

'FJic corpuiflcs for hcmoiylic experiments am 
obtained bv the defibrination of frMl^ly-drawji 
LInod nmt thp removril of the fibrin. Ufiiinlly tht\ 
arc made Into a G per cent^ aufipenaion by dilution 
with iflotonic (pbyfliolo;jie) eult toltition, InflR- 
miieh AH tha senim vh'wh in prvfienf may interfere 
with th* adion of the complenjent or amboceptor* 
of tlic hemolysin^ it is customary to remove it by n 
wa^ililng proee.w. The C per cent, emulslim, or the 



nndilated blood ia cenlrifngated, the OTerlying 
Huid dnvni oB by ntoauii of a pipetle and subrid* 
Uiifd by frwii salt solulion; the rorpiiscic* are 
tiioroiig:h1y miied villi the uew solution and Uie 
process of ceivtrifu^fftlioc repeated, the corpiisoles 
{tnnlly being dilated to tlip origins! voliuti? »it.b 
Bait solution. After from i-vro to four waaliinfra 
nny restdtml serum ujumlly may be disrcgnrdf'd. 
To tcfit tite IjctiiolyLic i>ower of a BVtiiin uue loe&s- 
nred idcctit^al quantities of the 5 per cent. wasEiod 
bliKwl itiln Pflrh nf n serira of tcst-tubpH by nipnnn 
of a. ^aduated pipette and tben adds increaeiug 
quantitiM of Ihc eenim to aiiooeEditig tubea. All 
tiitH4 nw l.hrn diluted to rfjtial volumes bv niPHnn 
of «aJt aolulion. as it is of wme importance to 
maintain a imiform oonwmlrution of the oor- 
pOHclev. Tlic er>nteiiU of tbe h)b*"8 are iriSxeil 
evenly by sbakinjj and the wncB in plarwl Jn the 
tbermoctnt for abont two honr»; this temperature 
u neccHary for corupleLe and rapid u'liori of the 
toxic Bubntaiieea. At the crd of this fim** t^fi tu>ws 
ftri' pbu'rd in fhp ire rhpnt nnd left over right In 
order that the cells may settle tfi the botlom, or 
»«diinentation may be aeoompltahed at once by 
cmtrif nation. 

In either case» Uje overhin;; fluid is colored red 
by the ditsolved hemoglobin in proportion to the 
Rxlent of destrirction of the erytbroeyles. In case 
•oJutloii hoi been complete, the Mdimcni ia india- 
tinot snd co1oHc«ii» biing mnde up only of the 
stromaLa of eellri, ^h^reiiH In ihe Liibpfl *jhr>wmff 
only partial hemo[yai« the nt^dimcnt ia red and ho» 
an indirect qiiantitntive ratio to the coToratir>n of 
!be OTfrlyinff fluid. "Ry miitabl'* varinlions in (be 
•mouDtfi of fcrum vtc^ in dilforeat fuht^, its 



nrKcnoH axd iMMuvtrr, 

oaci duioliiBf dose for the ^Tm volmae xd cor*- 
poicte luj bo fletenDined. Attbotigb tbe tcra 
h«tnoljna U & pcrf«cl]]r pn^r onm, w9 are to «a- 
denUkd that «eraras ctoaQ wluti^n &f tfae bemo- 
^bin, bvtt Dot «a1ntioii of tbo wliolft odi ; vo spcdc 
looAcly of solution of the CMpiueltt. 
BtmtimrUj AlitT BordH b^d ahowD the uuJosj betwtea 
^.n**!"^*! boctffTicidal and boixiotjtic fwmm«, nrd afur tbe 
ijrit^ "'ii^. pheoomciu of EnairiJraLioD and TeactJTauan had 
been developed bj Eordet And Mdohnikoff, £2uitich 
anrl Morgenroth un'lprtocV t^^ eli:<Ty of ambfKvp- 
ton nud ccimpIumcriU 04 Uier occur m temoljtic 
scmms. The facts fl***crtmTicd by thenk and tho 
nn«(hodi of r«««aTc}i Mthlch Ihey d^riwd liavo pro- 
ridtd many inrotijratora vith a etartin^ point for 
worlc of tho highnt importance conoorajng the 
iNkcl^rkidal >f«ntTiia and aiiti bacterial irimnnUj, 
tin^ their intcrprctattonii. moreoTCT, (crrcd to ex* 
tend the mle-cliRir theory of iBDmBuity to its pfM- 
«it oamprelierwlve limitx 

For the jflkc fif oonvcmVn'^c one rnav speak of a 
heated immTine eeniri, or one Ji which the pom- 
plcni«lit has become inactive from a^^ as a aoln* 
tioB of amboceptors, di^reftarding tempor&Tily tha 
B^aiitdHBf precSpItin« and perViajM other bodies 
which the wrnm contaiTit*. A!»o, since fresh nor- 
mal ffi^mms are rich in complements and usually 
conEain but a «malt amount of any one nmlmt^eptor, 
th^y may conveniently be considered as solutions 
of complementa; yet normal scrums mav not be 
cousidrnvl OK jnirii rnniplemciit nnd useil ns siwh 
in unlimited quantities for actual experiments, be- 
eanae of the bflcteriolysinfi and liemolyains which 
many ronUin. Only n qiinntify nf (lir nnrnial 
ecmm whidi in it^eif \i not toxic for tlio cell 



may btt uwd f[>r i7omp!einenting purpofics, and Ihia 
majr be es low as, or Lower thnn, O.L ex. for a par- 
ticolar eiperimeat. 

As poiatcd cut in the preceding chapter, the 
CombiDOd action of amboceptor and oomplomoDt u 
mpcMmry fur tlir cttntoxif? ncftitm nf n sitrrum. In 
mv of ttic foci that the tciic power b lost by ex* 
poflure to that t^mpermurd irbiob destroys t^omple- 
mcnt, it wetiiK that thu latl^r in th(v artunl Ji»- 
Kilvinj; or toxic substance, ^vhc^eaa tho ambocep- 
tor miutt pUy *ome inlerm^Kliary rflle. Invostif^a- 
tJOfiA hive sh^vn thai (be lw»> net (ogd.her in n 
Tcry definite manner in that the abaorption of the 
tmboc«pto» by the cells is a pn-T^quUitc for the 
abforption and action of the complement. Thia 
may be veriAed by ftuuple tsxptnnmiiU: Mix 
iTjIlirocytai witti the homologous amboceptors, 
and after a period of from twenty to thirty min- 
mea centrifuj^ate the mixture and remove nil the 
fm* ^rnim from thn cnlls by rppPRtprl wnshingK 
with isotonic aalt aolutioii. U the cAU are again 
Biu^ebdcd io nit lolution and n amail nmoimt of 
complement h added and thoroughly mixed, the 
hemog^loblu id dia^olvcd out; a control muat, of 
coiirve, ahov that the complofn«nt n1oii« hoa not 
tlic dif«oIving pover. Ttie n«uH iudicat^B that 
ttic erythrocyleA during their contact with the im' 
mun« w>nim had absorbed or combined chemically 
vith the antboceptora, and tbit the latter remained 
tttaehed to the colls in fpito of the wo^hinffs to 
whioh thi*y vere ffibtnitted. 

Jt would seem that the union of amboceptor 
with cell haa tho efTbct of Tendering the latter sus- 
ceptible to the action of eomplement. and for thta 
maon omboccptor-ladcn celfa an spoken of as 

Horn or Am- 



i^nslnu^ axd luuvNtTY. 


4>r'l*' «f Ac- 
tlan ul Aiiiitu- 


ftpniitixed cells, Ho&fw^ acconling to tho crIIm and 
MHinu eiojjlo)^, we may refer to aenaitited 
cryllirocjic*, sisneiliaMd Imcltfrio, etc. The experi- 
ment IH cfllled the aen«itJ7;ing, ahBorpticm or bind* 
mg expcriniiMit, Au immune serum may be de- 
prived of oil iU nmbooi^ptore in the bindinf; fix- 
pepjintnt if a sirlTicionl. qtkAiility of cells Iim been 
u*ed, and it would thereby be rE-ndcred iDca|>able 
of further rcJictivAtion by the eubi^uont addition 
of complement 

If, injitcnd of porfoTining the cxpcrimcut m Ihd 
manner dc«Til>ed. the process is rerewpd no that 
tlie corpiiffcled Are firvt treated vrith the sotution 
of complcmont and then vith the nmboccptora^ the 
rofpimcfe* are not hemotywl. DnHn^ thi* wnnh* 
injr 7>rocrte thi* rnmplemeut is entirely separate*! 
from the celU, and from this fnet it ia clear that 
direct union between corpHscle and complrment 
docs not occur; oaly »enBi(iifHl cella take up com- 

The quetrliuii £,» to uhelhrr the corpnMlcfl in 
tnkinjj up amboeeptora do eo by chemical combina- 
tion nr by phyaicnl ftbeorption Iins bwn coiitendftl 
with some vigor- Ehrlich bolicros that the procc« 
in one of elicmioal umon, and if on« adherer lo this 
virw it ln'coims nerf&aary lo nssign biiidin;^ or 
baptophoroufl jt^iiffi both to the red blood ccUa 
and to tilt? smboci^ptoni- In eontra^t to another 
baptophore uliicb the amboccplor |ia$w^asfn and 
which will be deBcribeil below, tbrtt one which 
unftM with thr iv!l U ndle^l the cvlophilona bnptn> 
pliorc- The baptnphetc of the ervthrocvte which 
cntt^rt into (he union Is an e^«ertial pnrt of n ro- 
c^ptnr of Iho re*! i^dl, om?«tucul]y we s«y ihnt the 
amboceptor iiniifH with ft rw-epTor of the corpuscle. 



The h^tlD^r of ovruin to 59* C. provide* one 
menus o! tppnrfHl i^oInUnrt of the nmboccplor 
from the complcmcni. but this is cot g tmo ieoIfl< 
tion ID that complement is merely rendered iuac- 
tiTe by the hent rotifer tlmn totjilly eliminated, 

Ehrljch and Morgenroth devisc^^ n method by 
vtiich the amboocptors nmv be f^paratod frora A 
fresh iuLiDUUc Herum without m nay wny iiijiiriitg 
the complement- This is nccotnpltahcd by per- 
forming the binding experimeot, already allndeil 
to, at a Jow t^mperjiture. The aerwrn, contmaing 
both nmboceptore and complement, ia eooled to 0' 
C or wlt^htly alx)ve. by mearis of a freezing mii- 
tnrc of imlt and rcc. A Mispcnsion of the homolo- 
gom corpuscles U cooled to the «Ame point, the 
wrum t% add^d iind the mixtur** maiiilained at 0" 
to I' C. for fnim iifr<'i'n to twenty niinutcs. At the 
end of thlB time the sensitized cells are removed 
bj iinmcdirtlc ct^ntri Tuition at a low tt^irpurature. 
ft&d arc Traahod entirely free from scmm by the 
nw of lee-oo1d salt s^Intion. Tf the ]ow tempera- 
tore hti* been adherfd to riKoron^ly And the work 
d^no qiiiokly, the corpuscles are not lahe^l daring 
the man) pnlati oris in apile of thft preaenee of botli 
hmboc^ptore and complement Furlhrrmore. the 
vojlied eensitized eolk remain intnct even vlien 
their tt!m|>Hr«tiirr^ nmr-hnji iUnt of t-hii UxTmfwtat, 
vhereu if «omc fresh normal serum or the aorum 
(torn which the amboeeptora were absorbed is 
oddeilr Uiry umlc-rico hnnohni* a* rrjidily nn wlicn 
treated irith the active immune &cnjm. The 
original immune serora is now a solution of eom- 
plcnient. and freoh rorpiuKlca which are o/Ided to 
it are not diseolTcd b«vande of the abftcnf<s of amW- 

lion RB|i*pt- 
■II* ■ I III tliv 



of Aimbao*p^ 


TKc« reaulls ehow the folloviu^ important 
facte: Amt>ocoptor and complement extit «ilc by 
s£de in an immune eenim. rot as a united eub^ 
etance. Union nf amboceptor with cel[ ia ind^ 
pendent of complement, the latter being tftken up 
onlv after tin? Mmbo.'eptor-i^tfil reanllon bae oo- 
cuTTcd. Ambo^:cptors rniite with cells at a. low 
lemperfiture. whergoB crunplemeot re^nires & 
big^ber temperature for ils union and for Lbe fer- 
ncnt-likc activity b_v whicb it dissolves or kills the 

Thjit comitltu«nt of tbe amboceptor which 
nnitcp with tbc coll hnw heca reforred to rus the 
c^lophiloua hflptopborf- Ebrlidi and hU follow- 
er believe thot complement in establishing con- 
nection with tbe celU does so hy combining with a 
§econd hiplopbore of t)ie Hmboceplor, ftfltr t\\v 
latter bos sensitized tbc cr>tbrocjlc or bacterium. 
Heno^, aii amboceptor bna. «s tbc name imp]ics> 
two receiving groups or baptopborea, tbe parond 
being: tbe complcmentopbiloua bnptopbore (Fig. 
7). It is bardly desirnble to diacusa varioua «- 
perinicnti vfh'ich furnish additional evidence of the 
amboceptor natiiro of the thcrmoetabile body. The 
observed phenomena allow OLe to a^ign to it the 
two hnptophores men lion ed. 

There ie a conflict of idea* as to the nature of 
tbe change prodiicecl by the ambooeptom. as a re* 
flult of wbich the cf.\h atv mndc flnsccptihlc to ibc 
action of complfmenl, Rordet speaks of tbe am- 
ho^ptor as the rubsimice seiunhQutttncr^ ibt? NCn* 
sitizin;; ffob^taccc; and hie conception of the ac- 
tion of tlie two BubstaneeB be has compared Toui^h- 
ly to Uie opetiing of n lock for which two keys are 
demanded. One key, amboceptor, ie needed to 

IHCOitAMga OF flfHOLVillti. 


prepftro die l<«rk for t^*^ action of the wcond key^ 
complement, the latter being tbe ono which really 
o|icais ii. 

IfetchmkojT appliee tlie naiue ihalor fo the 
Ihcrmostabile body, having in mind the action of 
a mordant in preparing fipsnps or othpr substance* 
for itte reception of a dye; tills di]T«T& little from 
pr^parntor, thf? word iiaed bj Gruber- 

The i^L-n. (if Klirlirli, howevt-r, is at 
T&nance with the cuacGpticma mentioned, for he 
•tea in tho union of amboceptor with cell nothing 
nore than the iDtHxiuction of u avm rhenticol 
•ffmity, i. c. one which attracU fonipIemeiiL and 
llii* ntw af!initj dof« not lit? in the cell itseif, bul 
rather Id the amboceptor (compi emeu tophi Ion a 
haptophorc) after the union haa ocGurred. Hoaoe, 
the tprms intmrrclinrv liiwly (S^uix'^hnnkorjier), 
cop^ilft of Mtiller. nad de^moii of LonJon. are 
words whjob cuTTy with thorn tbo meaniutf that the 
nmhornptor flrat laniira wifh iJic* (rll nud thpn ntrt* 
a& a UiUdrip tmbAtance through which cooiplement 
finally in put in reflation fu the o&\\. This ahf> ia 
the meantDg emWdied in the aniboreptftr of 
Ehrtich, tlie word jndieuticg more accurately his 
oonppption of tho methwt by which the ^ibstanee 
act« as an mteniieiliary boJy. 

If we coiididor it ^etablishcd that in the procKs 
of rytolynK nnirjn nt^cura |jf»twfvn complpmfnt and 
amboceptor we must at the §anie tirae amsix a 
haptophoroiu j^up to complemcnL Union would 
b« impoittihh' without it Corrfiborative proof of 
the eriattnee of this haptopbore lica in the fact 
that fmmutiiEzilion with complomont roaulto in the 
foTiDstion of anlicomplement, a prerequisite for 
irfaidi ia UQioD of complement with cell reecptore 





in tho imnuoisod aatmal ; snd th» nnion, it «oona« 
QflMcsarv 1o aflsiune, takett place lliraugb a btniilng 
j^r^up. Tl>^ mcTc possesBwn o! n hoptophorc, how- 
over, d<we not *o*H)uct for tlw fermeEit-like ftctivitr 
of compleiiejiU Thf- liitter i!liiiracteri»Uc miiitn 
m tho mcallcd Kyniotoiic |m>iip; hcnec, comple- 
mntt, Variitg a binding and s toxio group, bna a 
Hrudur« like that of a Uisin. 

Sooicirhat looitcJy wc have i^id that the inoctir- 
ity of a mthtti which ha« bwn heftt^ to 56* C- 
depends on destruction of the complement Thia 
te not strictly trut^, hawover^ for »tich troBtmont 
doibojrfl ooly the vyinotnuic group, the haptophor- 
Otti MWtitutnt remaimos luunjurcd. Complo* 
aunt altered in thia rocpoct ia callod oomplamfa- 
loid, and it ia aoalogDna to tmotd, aggktiuoid und 
precripitoid. Two MMUlial fAeta |eo to Ahow that 
ihU a i\ie pritictplo change wrought bv hMting- 
Firft, 1h« fact atalod aboT«, that immunuatMn 
vfth oomplotnenCoid. cniuca the formation of 
ontironiplrmmt Snx>iid, mmph-mvBtoid mAj 
oxfwd tnic cocnplcai«Dt in its affinitj for tho 
nahoMptor, nnd if cenntood celli on tr>at«d with 
t aentm ooutaining ■ miitaro of conptpinent and 
oonnpJcrocntoid, the litt«T ma^ oeenpr completdj 
tbo oompltnantophiloua hapti^iboiw of th« ■fnbo> 
cvptora ukd thrua may hlocic th« v^ for nctton en 
the poH of conpkment. Tliia v mtnin the ope- 
cifie inhibition whk4i ha« bMn mentkoo'd in eot>* 
Mctioa with toioida. a^lutinotda anil prfcipi- 
toiil8. This ie Uit C^mfUmrtttoiJ*V9r9i9pf¥mf 
(rompli^tiwatoid obatmetion) of RlirlMi. 

The amboceptor, aa the chameierotJc propert; 
of a baetmcidal or of a hefnolytie aenun, i« n i^ 
eifte ptndnct of the ismnoiantion, wlierwa t&t 



^^M amouni and character of complement in tJio im- 

^^1 DlunbMl ut^iriiail niirWi^iu tUtlf or tto durij^, 

^^H ffc arc, of coiirnc, obli2*>d to conaHcr the auibo- 

^^1 ccptore n8 a product of tin? civile of tlie body. In 

^^H iy»e terminology ut Khrlidi, IIk-.v irv iliVjinlnJ cell 

^H ftcfiptord. ftnd ^ith tiidr tno hnptopliorrfl ropre- 

^^P i^nt a mor^ complex Alructure than eifti^r th« r^ 

r \ 

FlE. T,— (iniphlc rvprfvnintlvu oX rertiitvn M ihu third 
«r<l#f. anil irf aoiu*? tiilDHantf iiuhliiE vtih anr of HinsD, 
Ci CfU rttvplvr lb* 1tLlr<T cHrr. na fiuiLwn^rHur , «, one uf the 
teptOpbom ^rf ibe ftiii1potti>ic»r. *r11]t vlikh tnoi^ fvnl Biib- 
■tUM <r prvituct of 1td4i?(litl jllilnlrcmllob. ft mftJ uulrc: 
f, tb< albtr U4ptapTK<rft of lhi> ■m&oPnilQ' *v((h wblPh rani 
^VDWDt nir QDlCe; X. <vmH'^'»ol : ^- f^" haptit^Tifirr, *iii4 
#, Ibt Vfoiotiilc fTDVp of complimimr rmm iCbiUcb'A 
"S<)iliiul)i>l F«rhf uoiva," ^Juihnacrl* 8j»tfm of H*tfli^Ui«. 

TOl Till. 

npUim of luiLztoiij) or agglciLtDlu; tho Utter Arc 
vnic^ptora; the former ambcKWptor*, and bccAUM 
of th^ bighar differvntiation Ehrlich hu lullecl 
tbcm rcccptureof IhcUiird order (Fig, 7). 


lypECTioy A\D iiiMcyify. 

«bil Low pi*' 

When micrcMir^anisTTi* gjiin entT«noe to the 
ho^y they tixv kilLi^l niul t^is^^IreO in consii)i?ra.bte 
maesca, Aa a r^auit of tlic aolufioD, c^rUin bac- 
l*ml oonstituflnte r*aoh tha drcalfttiont and 
iiTiKing tliPiH ari> uitflts.'uli*i* or rw^pplorn wliioh puw* 
«es8 liaptoplioits capable of imitin^ with a par- 
ticulnr type of fLnil>oc*optar, the lattor boing &u >u- 
tcgral part of some tissue cella. This union hav- 
ing tiken p!ttcc> an alHnitr for circul&ti&g com- 
plcraent mav be cr«!atoi) aa in the t«^tube ocperi- 
mcftts. Wo hflve thus the pnssniilttv of stirnnla- 
tion of ttie cr^I hy the bacterial constituent ilfielf 
efi fl to:iic or unti^uaJ food substAncc, or the toiic 
Bctidn may be cbitW by productu i>t diaint/^gra- 
tioD of tlic baclerial .lubst^nce. the dUintcgraticn 
having been af^mpHshod br tha digoative action 
of the ("omplemfiit which v&% Iskvn up by the am- 
boceptor. The c-IT«ct ia that of on unuBual etimu- 
lation, in rrspfinse to which th& wll, if not fatttly 
iojuied, reproducer manj amboceptors coinepond- 
tnjc to the typ« which was ooeupied or injured. 
Ai in Uto formaticn of other anlfbodict^ thir new- 
fonncd amboceptors reach tbe gcaem] fluide of the 

Concerning the epocificity of aenimliemolysini 
and anriim»brti't#*r(olygins for their homologona 
<x\U. we, of course, refer to the Bpecificity of the 
whole amboctiptoT'Compiemcst oomplesL It ia nec- 
«ABary to throw the To«poasibilitr on both cub- 
atancMj beouiie nf the variations which &xisX 
moBg coniplesuenta as well us among unibocep- 
ton. InoomueJi, however, as tlie heat-resUtant 
body AtoD« ia ifier«ae«d during immuiuzation or 
infection, the grwter part of the spicificity would 



teem td 6epentl on the nnttfri^ uf Uie aniWcptor 
rather thfln on that of complement. 

AI) bacteria vhlch stimulste to the fonn&tion niiri^rUi 
of h*[L*tericidal seniins <3o fio l>^-atise of certain re* "^p*"*'*- 
cGptora which they i^of^cee. Thtst sre, of course, 
ftliftlogoas to th« recoptoru of erythrocytes which 
cause Uie productiou of the lit^iiiol^tic bodies it^ 
£Gruiu. Bacteria ha\c, in a-i^Jilton, many other re- 
<^p(ors, Aome of vhlch oause t^ie d&veJopnient of 
ajr^lutinins. In the Ifttter instance we epeak of the 
afglutinogenio receptors of tlie cells, but there it 
no immt of wjual cnnrenienci? whi^rh ia iiseil lo 
dcngnate tiie receptors which stimulate to the 
fonn&tion of amboceptors- Ko two miero-organ- 
han% cnriUiiti nil idenUt^a! receptor appur^ttus; if 
the contraiy were the ca*e their ontiacnims would 
coincide In their bactericidal action. TheTcfore, tho ' 
cdl reccplori (nmboccptorg) wilh which thffy unite 
dnriQi? immtiniitatioD differ correepondinglv in 
lh«lr ertophilou* liaptopboren, Tho cylophUou* 
haptopborc of the typhoid amboceptor l^nda iU 
fip^iilc connt^art in the typhoid bacillus, and 
finding no suich counterpart in the vibrio of chol* 
era, the Utter can not be aenaitiicd by the anti* 
typhoid leium; on this fact dep^^nda Uie epocitlcLly 
of tlie w<?rum. This concrption doe* not iutiirfcrr 
with the cxplanQtion of the group reaction among 
bact«Hddal aenims, for it ia conceivable that Di« 
colntt bncilluff, for cmmplc, has, in addition to 
Ihose roccptora which eharactoriio tbc organiem, a 
imnll perconlage of rcceptena which are identical 
with thoae charactcrinng the tA-phoid bacillus. In 
accordaDOfi with thia poaaiMlity an aniityphoid 
*mim may well, aa tt doc*, »how lome inrrrftKed 
bactericidal poTvr for cl»ely r^ated organiflma. 




llcncc the cxpliuiiLticn of group bjiclmoJTEiis ij* 
WenUcal witli that of ^^^^ aggluiinalion. 

There is ft wit!e dilTercfiee of opinion regarding 
Uie iintlj oF tH)iTi|ilt'int"iil, i.»r aleiiu, x\a aynonrm. 
Bordrt and hi* foUovrers sUiiri for the unitv of the 
oloxin*. and th^ir iweiti'^n ry^ste on the fact that a 
p;ivpn nonnvl wriim may hn nwd to artivafe many 
(lifttfrent fttiiWi^piors. W« aUoulJ appreciate thjit 
ttiia phenonicBon miglit depend on the broftii ranpo 
of aotton of a ainglo oompkmcnt, or on ttie pre*- 
enw of <Tiffefvrrt eomf>lementa each being sperific 
for a partiCTilar amboceptor, Khriirh njid hia 
fdiool take the lutte- view an*! have Actually deen- 
onatrntnl a multiplicity of c<om[il<^mpi>U in a fi;« 
instaxicce. Hhrlich ani:t Sachi treated freah cor- 
rul amtmii (conip1«m«nt) in vsrjona vaji, mch 
aa tlisvation trilh papain, parlfal rlntniction with 
ftlkaliee. hwil, ctr» and were able by tlieac tncthocb 
to deatroy tho oomplament for Dne kind Of ambo- 
ccplor, while the aerutn attll rrbiinad its powvr for 
ActJvfttiMj^ other ninboceptora. Accordingly, U 
Menu cfnar that Ih^ ability of a ROTmal wrum to 
■ctiTito a K^^^en ambocepU^r ilepen^s doI onW on 
thr prMenM of c<Maipl<^in«nt in a general aow^ bol 
w the praiL-iMw of a suitable complamant^ i. o., OM 
the baptopborc of vkieh oomepodda to tbe ami. 
pImentophiloiK haptopLore of tbe amboceptor 
THJa point i^ of fttmX imporluuv in nfeceoM to 
tbr tnatnfnt ef inf«tftioua 'Ammm vith mtilm] 
ttfMl aocui^ An* tbe tOaajr of tW mwB vwU 
t» dapaad <m Um Mraawtion of ^il trtrH 

' i» c««l«Mtloa Ttlh tba amb««itMi. 
er « tbe ««|.» of a^ «.i,.pl,,^i i, ^j;;^ 

mMrieuesT avd ASTtcoMPLCU^r 9» 

AdtM proof of tb« mnltii^ici^ of conpknmtc 
ka« bf«n oUaiiw^ l>y etperlnentA with iDticotit- 
plcmcnU. \9 stated, the Utter Are ottninccl by 
immtmiutioii of nitAU« jtnimaU with nomuLl or 
iniDiiiK aCTsnui Thidi contain comploiuait or CD«i>« 
plcoacat^d. Wlwfl tbey Arc miied with tbc hooaolo' 
^u coraplOBCEiits the haptopli'^r^ of t)i« lalta^ 
tm bound bj Kkcaim of tlxr hn;)iaphotT* of thr anti* 
covnplcfnaoU, Hie endcnce of this untoo Uce In 
the fu^ that a C0fnplefn«nr whkh haa been titttod 
vith its apedfic tDticompIcfocnt la no longer obk 
to artirat^ tke ap[>Topriat« ambo^ptcr (p. 2dO). 
With properly vclrrtj^] *«TDtnK. it mar be fihown 
that a fri^«& anticiMnpfcmeot will nrutrflluo a f«>if)- 
ptPTit^nt vhieh ia apacific for ddo amboceplor, hut 
vill Irtvv iu> elfert on nxiotber fompltmnit vhich 
activat««i i <lifl^r«<it amboceptor. H«ii>c^, <oiDp)a- 
inentailiir^rat IcHht in iMft r«ip«*rt tJiat not all haro 
identical haploptiort:!. Imtniitiinition with knoo- 
n^=, MU vhifh <^>nlflin <v>rip!pm**nt, aliai raniH^ 
llic fDirnaliiru ut aiilicamplniir^ut. Bulb luiti^rnl 
aod acquired antibnotcrtal immnmlv may be lavi- 
ffied by t1i« injcdion of nnlirnniplvriient whiHi ii: 
homologoiitt to the compleinei:! ct llit animal. 

Some time ajp^ KUrIicr!i cipr«(4<xl tho opinion 
that an amboc^lor in cprinin nuav, maj ha¥o mora 
than one eomplemealopliJbuA liaptophon! ; in 
other u'orilf. thnt it may be a polyce|)tor rather 
llian an ^fTilKjcvjitor, ThiA hns a^n been pmpba- 
ai^ed reccrjtly by way of explaimni^ the ability of 
an anboe^pior to absorb from a normal ccrum net 
odIt th« coiupl^nieiil wliicli 4^ves lo activate the 
amboceptor, btit al^o othem which happen to bo 
pronent in tbp serom The former ifl «poken of m 
the domiimnt compleirtent and the latter as non- 



tvrwmoii tMMCxnr. 

lU^Bte* If oBt hMntmiMa with on immuae aeron tb 




iDAunuch. howevei-, di the immune oerum oontatoa 
amboceptors aij^. tlic anUgonistic action of IhQ 
antberum may dejiieiid, in ^jart^ on tbe pre«i3rice of 
fintuimbocc|itoii^ Dittcrcntiation between tlie no- 
tion ot anticomplement and antmmboccptor is dif- 
ficult, but il taay Ijc accumplialieJ in curtaiu caate 
b}' uppropnntr binding cxpi^nmcnta. Seium K an 
inflctive humolTlic serum, i, e., n sointion of nmbo- 
ceptora aud complement oid, is treated ivith eerum 
fi. Serum H has been obtained by immuaizntion of 
an animfil witli seT»m 1, and contains anticomple- 
nicrtt iind posaibly miti;imboceptDrs. I£ serum & 
contains only anticomplemont, it %n]l have no ef- 
fect t>n the amboceptors of senim 1, when the two 
are miied. 1"be amboceptors arc free to seneitiwi 
oorpuaclea which may be add'^d, and tbe latter vhan 
sansiUxed undergo hemolysis in the prcjtence of 
complement. If. however, eerum S contains anli- 
amboceptors, eitber the c>'tophilouB or the eomple- 
mentopbilous haptophorc of the nmboceptor will 
be bound. In cither case, corpuscles which aie 
aAAeii subse^jucnlly would not appear as fienaltltcd, 
for if tho cjto[khiIoTis hnplophorc hftiil bwn bound 
by antmmboceptor union between call receptor and 
nmboctptor oocdd rot oimr; und if Ihff comple- 
rnentophiloufr haptophorc had been prcix^cupied 
complement would have no elTeet tven it the Amh<h 
CBpton hnil iinitrd with Ihr rr11« by thc'ir iinbontid 
C^rtophilou8 lifipt<:*pitL>rc-«, l''hrlieh an^l Mi>i'trenn>lh 
(fMiifmitrufinl *uth uTili^tmliCKcptorv for (^Tlain 
hemolytic serums, and it was their I'cUef that tbey 
combire vfiHi the cylophUoua rathot tlian with the 
compltmcntcpbilous haptopliore of the ambo- 
«ptoT, HowQi'er Ehtlich haa rocently been ablt 
lo ptovo thp aecnrronro of nn nntibody for the com- 


isrmjnos asd iMMUxtrr. 

of ABllnni-' 

j)kirieiitop1it!<jus ]i&pliip1iore \n one cMe., Pfciffcr 
Aha rcporhi tKc df^momtroticn of ojiti amboceptors 
for tho upwifio amW^ptow of flrtiHiolfra »*niT». 
Tilt fiosttbiHty at AiUmiubuceptur fDrinatioik iB one 
of practical brarinf;, in view of tho foot that the 
pr<i]fin;ri>t] tii?aVni«nt of a pitHent with a hnc^ffri* 
ci^lfll serum mny result in tfie (^etelopaicnt of ?iich 
«iitibodie«. If prfttcnt in cnilidunt amount Hvrf 
vniiH romliiiK* whhi n**« Hmboc^jijor* whirJi virrt 
injodd Ard Oitu deviftt<- th« latter from tl^e bac- 

A ph^tomonon eqnally of tlf<nrelica1 anri prac- 
fiofcl imporlincc has tft do witli ihc k» called ilfvU- 
lion {JM^fiL-fift^) of coniplini*rnt- It hns li«."ii 
fouuil that tlie action of a bactericidal or hemolytic 

^mEs^^^^^m )i \i y 

Viff. ft^1im*aiiti« «vv«ukiB at [iMf'iriBT TW frw 
•■WnvtHv iBT* PBBtaaa siifc lb* rninnTi cowti—a c 

h**» > <w vkldb liftn oklud vltH iM tertcrW «U (ma 

eenim is kwencil. if a j^raat cxnw of mmAoa^tmr^ 
oier c«inipl««Dcnt id «dd«i|. Tb explain tKia lact 
Xeusrr and Wtcbabei^ Iiatc nppaw^ thst vbM 
•0 mataj atcbwtpton arc pntf«b| tlal all can not 
be taken up bv tlie c«Ua, tlwat vtiM maav h«e 
at* ablo to coiAbin^ vtth aooaa «f iW voaplemcnt 
whkli i* pramt «d thtt* prermt the act^aaraD of 
the tatttf to IKc ^enaitirctl cells ; th»t i« to ar, tt* 
ctmplemot U diwrtftl fixiau »i* istiur^i dimiioB 
of artiTitr (Fin. >). T^ aiMWa Id a 



tlon of the ^mivTOi] <^IU hcmi the dt^tiin of the 
conipJ«iiiciit. TI« phriiOTrii^ndii l*(l Wet'hsbcrg to 
BUggC«t ^t in tbo llieroptTiitic ailmioistrntiou of 
bactericidal senima il may hv possible to give too 
much of tbe scnun. Altliougfi clivcraioa of com* 
pUsaeat U a domoDatratcd kct, ite im^artancc ia 
tcrtim Ujcmjn? iir pi?rbnpft not rlrflnitely Betlled. 

It i< of iiitrreKt tliflt uinljnfH.'ptors nre wIMy *lis- 
tribulcd in the animal kiugtTom. and tljat In cer- 
tain im^tnnr^ th<7 may he ^icmonMnitcH in the 
aecretloEs. It hna \onf^ been Uco^n Hint the 
rcnoms of many ^erp<inls hnve the power of do** 
troyiiij; rfd Mood cciU, A given venom rriiy 
ContaiD tevci-al toxic aobetacceB, nnd the poiiennii 
ofdifff-'re-nt «prpfnU hy na rnimit* r-niiiaidr* in ilic^ir 
toxic propcriits, Cohn vcixrm contamv two well- 
kcovB toxiI^e, oii« for the D«?rvouft tieeui? aod ono 
ithich difleolv<'a cmhrorytt's, tho npurototin having; 
tli0 gttTilnr p;Uh<^gcnic slgniJii'Aru^i;. <*Dbrn vi-rioni 
abo ajfftlutiiiatt^,^ i^cd blood corpu^le^. acd Flt^xnor 
and Xo^udii found tiiftt it ^^ontJiin^ (pecinl toxin* 
for the It'll* of vrtriouM urgiins (c^Uutoxin.-i). Tliu 
vcDom of tbe rottU^uake. on tli^ other hand, ia 
neurotoxic to a 1o^ ds^o?, i>nt Ua» a pronounce 
tufliience in cauflir»g cnpiJUry li^morrlis^ea. Tha 
UtUir power I'Icahi^i 0s?ni>e« to a toxtn for 
endothelial cell?, vhioh lie eallfl lictnorrhBi^iii. 
Throuj^lr the norku litjlh of I'lexiKr itnd Nogtuht 
and of Kjea. fact* were learned coticeriiing tl»e 
bcniolvtic toxin of cobra i^nam, urhieti tnftv he ot 
grrat imporunei? in pmblenia of |nD«ral inunun- 
ity. It n^nin that the hemolysin of rcnoiu 10 an 
ambofxiptor rather ihsnn a toxin of the L$ua! 
nature^ ami tliat :(i^ aid of LomplrMicnt ii n*cv«^ 



tyFECTiOX Aiit> SVliUyiTT. 


mrj fo7 iU loxic 4ctioo. The xenom it^lf cod* 
tains only the amboceptors, hence the toikity oC 
tLe tubAtancc depends ou its being com piemen tr^ 
afkr it ift introduced inta tttc body. *l'h« poi&ce- 
■Jon of miitabic! complement, therefore, U a <ourci> 
of dango* in this iofltancc rather than a means of 
protection Iot the indiiidnaL One may rery well 
tUBpoct that n Nimilnr rclatioanhip is pos»bk in 
connection vrilli other fubetancea wliich are as yet 

A frt/"t of ndditional importanre is that ttie am- 
bch^Rptor CmiU niiitjiblc C{fnij>leincnt not only in the 
somrn of the ftnirnfll bnc it may also be octivatad 
by A compleiQoiit which tlie erythrocytes tbera- 
Mlfta eonUm. Kyco apcoke of the latter oa cndo- 
Mmp1am«Dt, L e., oidooeUular compleinent 
* V^SV" ^^ attempting to diccover the nature of the com* 
plaoaant whioh is prcwut in the crythroc>ti», vari- 
oua lubatancQS «iiaiti[i^ norMinHv in Uie r«d tvWi, 
&■ cb(4MtvTin and lecithin, ven oMftinctl in part 
fMm a«d Uvtlr acUvatiiig pcv«r for thf cobta aai- 
bocopbm via IwM in rQucBnt-glaw eipenmcntiL 
Plua tiiia irocit tl vat kanod tK«; )cdthiti> a d«fi- 
i^M^r kvawn dun^cal aibitan:^, hi« th« actim- 
in|t po«<or. and ll waa. tbere rovr, aw>ma ecl tliat tbe 
andoMWpbflMnl a( «T7tkroc?t<a is MthiBg met 
or baa ttia» Mtkba. All aq uto ^ta i ooDtab 
kaWhln« ^«l ml all at* a^MH^r Pim^tiUa to tW 
tMw it ymvm to W# imM« «( aana eoMple- 
vwmlitlkal ia to m^t« ««Mk<«tbitar Ifcittuzi 3oec ool 
•C« M gw|fcawt vM f«Ml Milfii II in all 
fMft U mM H MoMiba Ma wWte it vaa 
niMMffv la imwM *a* *• WvMMa fa tha oiUa 
u4 ttM u^iabal iMv W waff* aaattM 



oiilj in a very tooM way, vliereaa lu ujore imi«I&ut 
celU the union is of a lirmcr nntiirc. 

The reUtionsJiip between cobru amboceptor anil ' Jj^^f"'"*** 
lecithin netrnv to be a. tctj definite one, for Kyiv 
iras able to obtain a uniau of Uie two iritbout tl« 
inleTTontioD of erythro^iee. The resulting sub- 
ataxtctf the cobra-lecitliiii of Kyea, is a eompl^eO 
torn and needs no fnrther activation. Wc Iiat* 
yet to lettrc of the true nature of this new com- 
ponnfl^ the fliscrivery of which »e<>iTi«id to sngiir a 
more intimntc chemical knovrletige of the evh- 
sUwcc« which are concerned in immunity* 

At!ccrdii]g In Bung I'vrithir its^tf hss no nctivat* 
ing povr«r for Anake yvnoim. He Attributes th« 
hemolytic nction of the product of the action of 
lecithin on v«nom according to the Kvee tochnic 
aa dire to pTPH^xiHtanl rmpuntirM in th<r Imthiu 
That hemolytic aubttances exiitt in uupurificd 
lecithin ihcre ia no donbt. The lecithin used by 
Ey«fl in his 9xp8nm«nti> however, vit prepnrGd 
with gn<jit pmuiiition to avoid Uit prawEUK of 
audi tiubatancetf. 

T. Dungem and Coca attTibtttc the action of 
lecithin or vimom to a splitting off of hc^molyttc 
producrU from Uie [e<!tUiiti anrl fail to obtain an 
'^antilecithid'' t»y immuniEatioa. They alao point 
to a similarity betvctrn Kyc^ nlemcnUiry analpic 
of tha lecithid and that of lecithin and conllrra hut 
analytiia. Their vievr is supported by Uanvarlng. 

Kycfi, however, bad potntod out the fact that 
elementary analytia !ft, as a general rule, ineuffi- 
cient to iIclrfTnine differences in *tiih^ur<9 ron- 
cemcd in Immun? reactJonA ind by a determina- 
tion of molecular weights sbowc tbnt cobru lecitliid 


l\rKVTiO\ AXD iMULWttV, 

«Iaii *r ml- 

BlruiTHl fir 

ha? it iriiK^li ]ai{-4?L- iiiiilei-iilt llian Widiin Ittt^lf. 
Ui» immuDizaliort of eninatik td protlacc id anli- 
locithid eil<?mlwi ovw a mtic'h largor period titan 
tltCTAu uf 1. Dim^L'j'iL mill <%ji^Ji- 

Jrfcilliin i* fl oolloiH. and io thi* oannofition it i» 
interesting to note t^int it tnay 1^ tised in combina- 
(loti with Ktill anoUier ixilloid in Hurli tnurmer that 
thi^ hcmolyei* whidi th^^ cniiBc i8 anabjZDQs to 
that proiluceJ L_v htiiriolvti^' ambocepUin and c<jTO' 
plfrmcntE. Ijand«tdncr trice] the effect of col- 
loidal tilido fteid on eryttiroc}leA which w«re en- 
tifF^Iy frivA fmni eirrum, wHh the ivjiult that the 
cOTpuaclfifl were a^iulicatcd under its inflaonco* 
It 4l«!Tdop«d further, howover Ihitt mlloklal aillcric 
■cid not onlv acte as a.n ofiglutiniii, l>iit atco mmu- 
latcs a heiuolyltc aiiihocoptor, and m the latter 
f^pat'itj ii utay h<? jii'HvatPil c-ilhrr liy tlit ordiimrr 
compIcmcM of srmm or by l^itliin. Iloncc, wc 
have here an m&lfiiice of the entire cytolytic action 
l>rin^ prrformml by twD known irlimnicala, nhtcH 
in Ihdr miction appear to be analogous to amboc«p^ 
foTK and ^omplementa. Yet even the aetloin «( 
thftu* si]l*1arir(^ Ir nWurr, for nTtJioiigh Ihc rhcin» 
icfll formulae of ailicic acid and LoriUun are suffi- 
ciently well knovn, lb* explanation «f thwr artiv. 
itr as colloids is cqiially obecarv with that of the 
albummeiia ^ubatancea, 

An<*t!n*r dr*™very whirh t/^ndu tn linn.ijr the 
iiankunr tTibfltancp* into clowr tour'h Tith pure 
eh«m]«try ift that of Hekioen ^novminf? the abfl- 
fty of CRrtain 4«lU (cttldoin cJiloriJ, barium 
chlorid, etc.), to combiin* vith complcmiot IP 
ttuch a way that the latter loges Its ACtfratiDt^ and 
combiDJD;: ftmciioit ia relation to ambcceplonL 
Thift wna i^cntfoncid ineid4^taUv under the nb- 


jocl of nntitoxiiut- The* ndivity of the compW 
moDt n Bgain rc^torod if tdo mbibiting aalta arc 
prM^ipifatcf) by ftwitflhlc rh^micftTfi, Th^ salts are 
used to siicL diluHons Lliat i\\ey tire Urgelv ioriur-il, 
and Macwftrinff bolicvca their inliibitiiiff action ia 
duo to iho formfttior of compounds of the po^* 
tiv<* ioRii with thi? complpmcnt, wsulting in Rich 
snbfttancca m Ca-conipJcmcut, Ba-complcment. 
etc. When tht- prwipitating chernieals arc aiklwl 
the ioTiB Rre frred from thi* comhinatSon. sd a rvv 
«Qlt cf which the complement recovers its activat- 
ing propcrtieB. It baa not ns jet been determined 
wtiPthiT Tsrifltionft in the gaits in th^ fliitdfl of the 
bo3y caiHtt? trhntigei in reaiat«Tice hy IhrJr action on 
nfttlT« complements. 

The work of FoirHtii, Haua Sachs and ToninoIiT. 
Bnitid uniJ Hnkrr )iii« whown ihnt rtimpliMni'fU 
may he diTiJcd into tvro paria by tlie sepumtion of 
tlia albunijn and globulin content}: of tho i^oram 
containing il. 

Nt-illit^r of thr?«e Iwo p^krU alone Ijmm llie pouer 
to brin^ abotit hfinoljiiiA in earpuBcIcA prcTiou^ly 
(OHMti^ted bv the addiliou of amboceplcr. WIlvu 
oomhined, however^ homolj^ta lakes plnce i» bpforc 

Abtorption of the Rl9btiUn frac-lion taki>ft plaa* 
when It Is added to sensitised porpiisrlen. Te^trlt- 
ing in "Pri>i*np!i*iawl corp".«"l(if" (Mii-h/ieliK and 
Slorirrtcy), which ttien undergo hemoly»iai en ad- 
dition of tb« atbumin fraction, The albumin 
frartion, on the rontrary. ie incapnbl^ of bemg 
houmi by iht atriffiiireii corpiij^clc:* in the abNcnoc 
of the globniin trnction. Brand therefore term* 
lli^ globulin fniclion as complement "iniddleplei^e" 

jiI^vIh uf 



■n^ deiignatCK tlie nlluniin fmctfon &9 compte- 
uioDt '*end' piece." 

The eiii3-pie<'<*, mEdille-piet'e nnJ aiitbo<*ef>lor 
bear the wimc relation to tucli other M whole 
oomp)«mGrtt Axnltoccptor and antigen. 

Thr.' iiiii?dl(*-pirt'n iR tharmcMfiiSilo whon attHclied 
to tlic aiuboce[jtt»r aiiligi^ii coruple:;, bat tbermo* 
Iflbile when tioflU'd alone or in wmbloatlcm with 
tlui vntl-pifirF. Th(* rr»]-puviT tt tliftrmnlnbilt^ In 
specific conipl«n)C&t dcviatios, it is the middk- 
pJece vhlch becomei twun4. ti^c end'pi«c Ttmain^ 
in^ free. 

Attempts to aMCrtttTi the lutorc of these two 
p«rU tv ftubfitttutjoo of hcithtn and oth«r lipoids 
ii*ve BO far been wJtVovt rtsuU m L'lpUiiiiiig Ihe 
ntttti* of the tvxi eonipoiK'ntfi ( IJcfnuin And 


coupLBU^^^T dkvutiov. 

!u !001, Bordct and Gengou oWrvcd that when 
An unti^cA won miiced uith its special; antibodj' in 
ihe presentee of uom|jlen»ent, the compleinetit wa* 
ftitd or bound And tliiis rendered iinavniUblc fct 
further it^aotione. This phenomenon hns ^iacebe- 
comu rtidi:!)' known as (complement deviailion^ umii- 
plemeDt binding, or coiupIcirtciLt fixntion; and the 
principle imdfTlymg it has beooaie of extreme 
vnhip in tbn drtpfminiiticm of thp jiresence of 
fftil>Bta!K«i wlioK iiittriiction ia followed by no 
TVAdily p«rcop1i]>li} roimU fluch as \yii9 or precipU 

It will be %eii Ihat »adj a reaction is analogous 
to curtain Hicjiiicnl njacUonK $\iL'\t q& the eoin1>ina< 
ttoii of ordinnry iiddH atkI Jilkdlics in whirh th« 
prtMDce of the ttactiom ia determined by the use 
of indifjitorc fuch ns litmui or pboaolphlhaloiiL 
Ttor\]et ;ii]d Hengou ui^ed as an indiestor a hem- 
oI>1ic system of eryihrocjl*fl with their ^ccific 
amboceptor. In thifl way, for iofttanoe, by mi:iiQ|c 
typhoid baeilH witb antityphoid uernm, incnhnting 
for A tinie and llien arlding mthroryV" wn^itizcd 
with their inactivated nnti^crum, it wn# obicrTtd 
tbal hernotyiiM did not take places The coraple- 
ment in tlifl nnlityphmd E^nim hnd hwn fix»d to 
Ihc tvphoid bacilli l>y tiie Ivphoid antibody and 
wflfl thm rendc^i) unni^iUblo for the h«inoIyiila 
of the AenHiLijed erythro^^ylea, auh§equently added. 
Bordct also abowed tl»t othci indicatora aitch at 


ft bicteriolrtie iysUm oouU be mod LmUad of 
bcmoljuv, in oirdfr to Utt for ll|^ binding of 
ConplABaeBt deviatjoo obviously bdonp la « 

ftod iiiKe tDDl* of atmt Kftre & rcrj cloae bearing 
oo tlv MObfliaiMnt deviation \yy iLeanfi of notigeD' 
tntibodjr ooDpIci it h well to reviesi ttiesi. 

Ekrlkli ft»d Jlorgttirotli made iim of lb« com- 
pfctftMHit iuhibttioiti or low«r«d t4B]p«rattiTe to 
Kfurftte cUKipkllWDt froiti HirilM)ci*pUtr. 

HcktofD and Riwdigirr fouud Umt tarbov iudji 
miffht rtndpr compUmait ifiectivo. CttitaiQ eub* 
fctsBCtt ttkkh iD ihema^tveft are hemolytic hare 
been ikon to uitft^niz« comptcmcot action. 
Aiikocg tb<*«« are to be mentioned bite vultfl, «ftli! 
of (Mit it-id<i, Uvttliiti d]n1»tcrtti unrJ other Upoirl 

ftiyjMM of finely divtded eubetanote have 
been daw»etnttd to inhibit complomooC «cllon 
and tke ft«»UEn|itx)D that thrir nbility to atitagurixi- 
rampWtnmt U due to tbeir adtorptite property i^ 
hii:bly probable. KaoUs, chalk, carbon, eand, etc.. 
bftTtt beta uKd in tluc vay. 

A vlda miety of oolkjiAal fiuti«tari(VA itaire Ikwti 
bbovn lo inbibtt coapkmetit ; eacamplc* of tbcw 
4rt ftlatiA, peptone^ alevrotiit, Alb^imo^i^, etc. 
Lattiy, axtnets of bacteria, normal inH pathologic 
tjann cvtrwrte aod tbe body jui<«» work ati corn* 
plesMfit inUbitor*. 

Bitfticll nod Bordet by immanuing a&iamle 
«itb nonnal «nn aaoeeed^ in proHnring nnunft 
btgUj aftta^oniallc t« eompIrfiiiTiit aHion, Accord* 
isf to tbv Ebrbcb ooooeptioQ. Xhtx bodies are to 

lymomoy or oouriSMEtsr. 


be Tfffarded ns distinct antibodies, receptor* of 
tbo JirBt oT-dGr. Moreaclii, lioirovor^ has throu'D 
i!o*/ht flo the c^iisti*n»*r of eucU distinct antihodiff 
for tho reaaon tiint ir using normal serum aa torn- 
plcmvnt a mixturo of proUtn ftub^tiiucej^ i« ti)K>d 
giving ristr. hi iiritiiunifatton. To antlalbuiriiiitnif 
bodies which read with the antigen to form lom- 
LiDftlioEUL which inhibit or bind eompIemeiLtH Stioh 
conil^inationii in the form of pr^ipitate^ may he 
demonstrated to set as anticomplements. The 
exutcnec of trut nntn't^mplcinentj", therefori?. 
vhilc not disproved, Ju» not b&ou fiatis^facitorily 
drmon strafed- 

Th« preseiioe of €«iiip]ei[ienioid in iaactivated 
scrum mny also net as a oaii^c of complement in- 
hibition b}' oc-uupjin^' the feesptt^r* of th« dull- 
bodj. VViien tlfejte various factor* whiuli ooru- 
plii-atc the complement Jl\ation reaction aie con- 
iidorcd, it wili h? eei^n thai grcAt carD mu^t be 
taken in boUj the teclmii^ and the tnt<;rpretatlon of 

The .-lubstnncr concerned in antiern, nntibodv *i»i"i" nf 
coiuplerneDt luaticD U obtained by procoiif;ea of i>v«iair»n 
imrniiniiation similar to those concemRd in oilier '' 

jintiboditB. In the one cwc tbc reaction is fol- 
lowed br perceptible reaullf. m the other by 
fiialion of eoinplomeTil. The f|Ucstion nriiu'<: ar» 
ihe antibodic»i in thi^se two l^inds of reitdinn iden- 
tical or not? 

Thnt th« [>omp1eni«Mt liKulion nntibody iit dtit- 
liml frutii pri^cipitiuH ijnd a^lutinijin ia indi- 
cated in different vr^Tt. Muir and Mnrtin« by 
immiinizin[^ rabbit* ttith (rninefl-^g wrnm, ob- 
fjiincd nil antibody i:apabK< of tximpiutnriji fixation 


iitvE€Tto?r xsa iumuxstw 

but trlilch coaUined no precipitin. Moreadii pro- 
doc^ in fowlg aotiEcruTik which waa hi^ in 
precipitin ofincTntrntiim Init did not prridTiw coin- 
plduteul ftA^Uim. Iti likiT iiihuuej' tin? (imstfiKv of 
antibwi^ compfciiicnt dcTiation m the nbaence of 
agghitiuntin^ proporlicu hi» \iMn\ noted, Tn 9^- 
eral, ctiiiiiilt-int'Dt devinti^^ii antrbody U destroyed 
at higher tcmperaturtt than &£glat]&ins. 

It is in lytic flinboc^^ptors flint <cniplcmcnt fiwi- 
tiou aiLliboJv Imt iu ^loeest analdfiv ami ojjlniana 
ai>> divided HH t€ the idenliti i:rf Oie two. Xehfeld 
And Uaundcl regard umboc^ptor nnd ccmplcmcnt 
fixation antibody as diatiuct from each other nnd 
applj" the name '^Borrlet's antihndy" to the Inttpr. 
They reach this eonclusioii fiom tbc foci thut if 
cholera Wi)U and their onti^runi arc mixed with 
oompUai«nt and a!lowt>d to act at 0^ C.^ hemol.TiiQ 
tTomplemfTZit i* alj^orbwi but not that Iltf^eft^a^J for 
baeti^nolj^iB, Th« ^nte mixture Allowed to act nt 
37" C. r^RuUi^ in an inliibltion of action of hotb 
(\)tnpltfnieiiU, The objectiou to siitli a proof liea 
in the fact that the dilTercncc' mar bo due to a 
dlff^ronee in the complementB accorcling to Rhrlich 
Bfid hi> vchoo!, nho ijidiciT in the muUiplicity of 
complcmcntA, Ncufcid ^nd Hacndct have also 
InmiuDiiied ^loiinalB with a oeTtain water vibrio 
and obtained a scnun wbich wn* hactcriolrtic 
against this vibrio, but not against cholera vibrios. 
Complement deriatioii, ou the othar hand, was 
effected by uung either of the two Eoicro- organ itnia 
aa antJgeD* 

If Ehrlich'fi deHnitinn of amboceptor as a sub- 
atauct^ vhicli unit«a antigen ntth complomeitt iB 
occsptod, it i» apparoot that the term will apply 

TALO^nox or c^mnMMKvr oMWiATios 

to "Beidfr^ utiwdT.- vKhW it m tdeDtinI 
with whci mboocpvort or xuA 

U vill be n«dil5 neo that tba tm>cCmii of com- 
pteMvt fintion likft och«r Imaiitti^ r«actiooa be- 
tvven BDti^ci aod AOtibodj: ma; b« oMd for t\tt 
iientificslMO of cither o£ tlw two bodic» coocvmed. 

Tb« oonplencnl fixatiOD t««t bti been i»ed Mi*ia«i« t«*«.J 
spsHiUj bj y«iaser and Swfn sJiniUriT to tlie 
prvdpitiD tcft for the difFcTT^tiation of protcittJL 

Animtlj art unmuiiui?d to A eeritiD proteilk 
t&d tn tottKnim is thaa obtained. A titr^tioa i« 
Iben msde wiUt knovn ljoiroki^it» SDtl^m aihl 
■iitiitodT, in mytDjr (jiuclttiee, to dctennine the 
■mOQDt of flDtt»«n]3i oecffiMTy to produce con- 
pIciMiit deviation. TZ.« (puniitT of notiiirnim 
fouod bj titration to be acccnarr for complement 
fixation in the proMDoe of homoloF^ouB antifen, ia 
then sdM to (lie wruin or protein lo be tMl«d. 
If thia protrin nnd thn inti»tiim An* homologotiv, 
ft completn^nt fixation viU ncmlL The method 
baa Iwen criticiwl because of ila extn>m« delicccj. 
It fi eatimntel Ibvl nmnuntii nt prclrin AubittaDcaa 
vill gire a complement Elation ttft which aia 
prcfeat in one-rniUionLh the qoantitT roqtiirod for 
n precijiirin te*!. UMenTiuTh ft'lviR?* Ihp rontrnl 
of the mpUuAi by llie precipitin test. AltJTOxigli 
othor antinEona tceh oa barterin may be identitlod 
hy eompletrient 6Kation. t)ie L^iiatenre of eaaier 
raethocifl make» complement fiiAtion of litUa ralv*. 

'i'hc cxittteDc« of ca»ier inethoda of dia^noafa 
reaiihs Id infrequent m^ b^iag made of tbe com- 
ptement deriation reaction a» a meana of diaffsoaia 
in infoctioos with organiama eapablo of caUiTn- 
tion. The preaence of tlic roactlon lina been 




deiBOMtivUd, b(nff?crr ta m large wunber of la- 
l«cttoM tjphoid, pnMjpboidp rtrvplococcBi in- 
fections findnditig tlnptocoectt ufcdioiis of 
fcatkt ftrcr), fsenmmia^ d^reoitcry, dipiitiitTu, 

Kolk ukd WuMnMnn Imw dnnoHtntod con>* 
pUnwot fiutico m ineninsiti« and aog^OGt the me 
of tke retHion to d«termine the fllr^ogth of men- 
Wforonripi antiivrtmi 

R^arding the pmcDce of antitubcrcaliii in tfac 
blood of Ub«reuloUft antmaL' and mtii, f^oD^ctinj? 
reiaJta sue nported. Jt vould appear that com- 
ptfrment fiiation mactjoti ig incoiietiiit dnnnf the 
OOVTM of tubertul^ii and that the reaction uci^ura 
more coiwtantly aft^ tho tit« of thefap^nlii^ in> 
oi-a!atiuiui of tiilienijiiti at*t\ r«[wrin1lY of i-rant* 
ftiorw of tubercle bacilU. 

It occiirteil to WadeermanD that by luinj? «■ 
unci* rif tiB>;iip« rontflining antigen, complement 
di-viati(]ii aiitiKudit-i mi^jht \n^ fuunil in infivLIoiia 
in which the antisen coold not be ctilUi/ated. By 
the uee of sfphilfltc tiaaucfi lie imitmnized apea 
againftt ejrphlliii ami by iiiiiiig sudi »jphitittc tissues 
»A iinti^:i:ii found complement demtioQ aDtitiodie» 
in the tcrunt of the immunitcd apce. 

Wuaarniann, NeiMcr and firuck, in 1$05. pub- 
liriheiJ thi^ r€«iklt4 of tlie^e i.'iperiiuenta togfrthoc 
with a method aduplinjt them to tlie aerodiagnoaie 
of avphilie vhieh haa beronin f^nDmonly known as 
ihe WaaaermaHJi rtMi-liuu, SiuciT ilw. yjiirnrhetea 
of ^Tphilia were known to be found in cxtrome 
nunibera in tlie livtr of (he syphiliLio fetiH, an 
nipieDiJn cJitfnct of Uitu organ whh u«h^1 n» iinti^en. 
To thU cjElract vaa added Ihe inactivated ^i^nini 

w-ixxsKMAKx HiAcrtoy. 


of the fluspected caw and after the addition of 
compicmonl. tho miiEtiiro nai inciiL^atod aii bovir. 
SJieejf'F eoq^iwlefl with spwific amboceptor were 
then addctl and the mixture again incvilMted. In 
rftM th« fyphiJitic antibodv wak prownC, compl«- 
PueDl iKH'ariiF 1)[>ij]ul iifid uo lit^iiuh'^i^ Lovlc plutv 
Upon K?cond incitbation. Through a Urge number 
of 1c«U the Wa^ermoTiri reaction haa b^n proT«d 
Iti be (.'liuniL'ti-riylii? fur MVphlliK. 

Th« idea of Wfltfiermann that the c^omplemcnt ^Biiir* n 
bindm^r wa£ dne to extraet of ^pirochetiv ne atiti- vr'wa*^ 
gtn and nppciflr amboceptor, soon found oppo^i- "**"■■ 
UOD. LandFtrijiTi. l^ltiller and Poeiifl, l^vndili 
and othrra tJiow^ bv the u^ of aleohoEic e:rtrach 
of norma] orfflnfi that a eubfitaoce eould be ob- 
tainrd wbiHi arled as antigen and could b* 
aubatitutRd for tlitr ?-xtta<t of Hjfphilitlc liver with- 
out changiDf: iht rcfulta of the reaction. FinQUv 
i( ha* )ii?w thotrn thflt mixtHre^ of lipoir^ sut>- 
MtnruvK or rnidr liuar fiTithin ci>ulil Iht cmiI a* 
anttfen, WaMcmiann pointed out that vhoreaa 
his Bi}i]eou6 e.xtraet of syphihlic tit^uef vn^ tlier- 
molabile at bciling. the alcoholic ^xttwct of nnrmnl 
or^ani vnti tli^rmoiHtahile : furtht^r that the aqueott* 
ntrsctfl of norriiJi] ur^na do not act t& eub^titutcf 
for aqiieoiifi cxlrncti^ of ej-philitic organ*. }U 
tiierrforr r^^joii'^h't^ hi* iirigicml idi-HH jlh to tlie 
tfpec-iHcitv of anttfvn sa correct aod held thai 
aqutfoujt extract of M^-phiUtJc lifcr uai the onlj 
eitraet which could he iif«d iritliont chance for 

8clij£mNnra nnd i'lnh^n have made a ^tuUv of 
the variotih extrsri* and roncind* thai the differ' 
mcv in heating iiqiteoLtFi aiid alcoholic e.\lracta h 


mrBCTiox jiXD luMUtitn* 


<]i»e lo Uic ftct that En lii« aqpuons extrftcti, a 
larsc uaonct of protein b pnMOt irilb the lipoid* 
itn wh^li xhe antigeoic Action (kpendp. and tliftt 
th«e Jipoidi b««omo bound to tho protein ihrau^^h 
lieating: fnrtlicr, they beli've tbnt thwr lipoifl 
niiliHtonfeti may be extratted with wnirr in BrpQi- 
ilitic li\cr li«caiL«e through dctrcnntitiri? processes 
lhe> tn'tomc split off, while in rortnn! orfion* tb«j 
iniirt bu tpViX olT by n^^ohol and ht'At. 

Tlipj rondiitlp llmt the siit.igpn U therpfonr of 
i]ou^«]M>cillc lipoid ntttirc and thflt it acts aa 
ntlivnting iht complement btrdmff property of 
^vphjlilic MTUHL 

Tho nAtutv of th» Ajbatanoi^ in the serum of 
■^>biUtJca nhich in ^iinhJuatiou vitli uangcn 
liUiftUs oomplfuitnt a£ti«>ii, 10 etill urknoiriu 
Kofuchi hn< chovp-n thiit it b«gitu to ehov tho 
•1TW» of h«»l at 4i" C At Afl' C it U waiewhit 
illtiiiiiiifaf^ ill Acttnty a»tl Ml Ad* C^ it« w^vitr 
M Ul. It \im beta tbou^lit of a« AS antibodj 
boMum of it« d«v«to|i«icAt with tii« ckrclopoKtit 
«f tito iltwAM uul iU dutppMTAMv with th< con 
b\ «^'iti^ trv«lmevkt. 

Ai sifti «i4i<^ in |b« bt^uuun^ «i ite cbAptvr, 
tW >«Hih^H vMtmibW u«*d fin ra»pkm»t ^eria- 
t' > ^ t*n w— tffn bAffa wmintm^kmMMf 

I^Vh«Wte Vj ^mt^ 1»^V ftW bAl« « llMiljtM 

TUCnSSO OF TTAffSE/fJfAJfy fliJACr/0>\ 2&T 

roqiiired for the l«t will Le described Jkiid then 
Iheir applicalion to the test. 

SlieepV i^orpusilrs mny be obtainei;) from ihe 
jopilar vein of tiio aEULial, TJie blood ia defibrir 
nated and ^rasliod by ct^ntrifu^iition with mit 
solution, the bbII KolutJon Wiirg L-Iiang^il LW«. 
A 5 |>er ccntv suapCDniou of thcnc corpuscte^ m 
D.S5 per cent, »ilt elation ia used for tUe test, 

Innt'livHl^d h<*innl}"tic Kpriim for shwp*s cor- 
pueckft is pn^parcd b; imiDiiniKLng ft rabbit ogninst 
ehoep'e t'oifuaflcft. The aoimoln ehould be injected 
itiCTRperitoDenll^ vitb ^asbed corpuscles lufido ap 
to the volanie of blood from whidi th&y were 
tekeu* by tiie iidditicn of unit ttolution. At leoft 
foar or five inj^ciionft ebould bf> giren at intcivfik 
of frum fmjr dny* tf) n wo^fc. and with aiuounu 
bcgiuning with £ c,c. ciml ciidiii^: with from 12 to 
20 c.c. The animal tihould not be bleJ befon^ ten 
dayd ^U&r ILe lA«t injection. Blood ia oblalno'l 
inm\ tlic mnrginnl vrir of tlir tnr uiid ulluwcil tii 
cloL 7he serum is then removed, Ii«at«d to 56^ 
C. for on^hfllt hour n&d atandardixod ss follows; 
Varying gradad amonntK of tbn mactivatod wnim 
plus 0.1 ex. of couipltmcnl (freah guinea-pig 
HFiUDi beet obtained by fifpjration from tliebcort), 
an added to oach of a nitmbcr of tuboA eontainUig 
I CO. of £ per ct<i>t. sb«fp'a corpuscle euepCTMion- 
Tbc tubM arc ineabatcd for one hour and tliot tobe 
DoUd in vihich the nnsTltft amount of kimEiocwptor 
(inactiTateil mlbEfa senim)^ piodaeed i-oujplele 
benolytift. TbU is called the hemolytic unit of 

The ontigen i« prepared by the oitractioti of 
miflccd frvphiliUc or noma) liver, iritli 10 volumea 


iXtfWrmJi ASa tMMtlMTT- 

of M per eont aJcDtioI for % vttvk ai 3T^ C, Tliis 
extiaet ii filtend And evnpf>ratcd by menu* of a 
r«n at Ji lompcrfilure belov 40' C. Tlie j»i<!tie 
ifl pxlraclml with etiicr and tli& cttirrr cTai>oratcd. 
'J'hitf rcitjduf w ajzniu tnkvD up in ether and frac- 
tionated twi(^e with dcetane to remora t])« ac«toii«- 
floliiW** lienirilvtir hubflianrpf. The acetone* iiuol- 
ubic ro^iiinr ill rvAporntcd t^ dryncia and extracted 
irith 95 per cert, aloohol. Tltm dilution u tued 
n* a irtork anrigrn flnd KitA^NrtDGimi^ in salt ^tiiliou 
are used aa material for leata. 

A titration ot antii^cn ihoiild l]i«n bo carried 
out ■« follav! A ^rum from a knnwn case of 
9>|i1]i]i^ -iliotjiil lir vbUititn] and 0.1 c-.r. of the 
inarlivBtfd K^mm added to ca*']> of a wriwi of 
tubm. Another i^riex of control* U Ent4e by tlie 
iiMj of a tiki^qLianttly of wai'ttvale^l normal apmm. 
To Mrh of ttie luW of the lc»t >«ri» jrr>d«d 
vttrrinf* atoo^inlg 4%f antijr^n an* added and like 
oiuuutils mMed ti> the cnniral tnbpt. Complement 
iKl C^. ia add«^ to mch of all of the tiibcK and 
tl>e aet in<Aihilfd taut botir. At tbc eod of this 
ttnw, two imit8 or wnhoc«ptiir for rt»««p*« «or- 
IMidea oud 1 e.o, of & pw c«nL attpensioD of 
•liMp^ cw^im^Im are acMfd ami the ttibofl imii- 
baln) for an<ilhrr Inur. The amalksC amoiinl of 
aiitijran whrcfc, vith the syiihililic atntm. will bind 
i<Qni|»baniwu h imU-^tMl bv th» tnW c<»Dlaiiiuis 
lh» tamil ^VMmiit^ of aiitipn in «hkh ImmItyU 
to tiot tiAe^A |ht«c^ IV central tvbe coalftbiu^ 
a hU «ttMrUl> Pf auti«v« but with MtmI scnim 
ahOttU be «<«M|>M*Jjr Keaftilywd, 

HivtMg »aia iUAdaidlMl Mil ttt%«i oiid 
ImhOtvtfr a»fcwej*ir, %U Wh vi ^ i*r«n ia 

qiKfUon U carried out as foUovs: C,l o.c. of 
Lnaetivated ^runi to be levtcd t§ ailded (o 0.1 e^- 
tti complcnirnt and thot amount of 0ntij:cn added 
vhjoh uat found lo be tho mioimum r^nired to 
bind complpmetit in t1^& preAt^m-? of 0.1 re «f 
fiyphilitic Hcnini- Control tiiW nrc made aji fol- 
lows: One pwilin; control ia iii&de aa Uio IcM 
serum tube biit with fl like qunntity of innrtiviitei^ 
btinwti ii}phi]i(ir H*ruiri in pljire nf tiu^ iu<nim to hr 
tcslH, On<: n«^aLUi' c^mtrol i« prcporcl with the 
^.Eirnt) (?omponc'nU aa tlio 1«Bt ecmm tubo o\<«p1 
that insdivat^d rnrrnnl Hnritm U lund itiEthmd of 
Ujc KTum to bi? ti;»1«tL Tltrec cuiilnil tubes are 
made witb the ttfsl eeium in one, positive acmm in 
a second and thfl Dormnl gnnin in thn third, ami 
mill Milulloti t<uli.*ilituteLl fur tin? bntl^rcu to ascer- 
tain vliether or not the t^runi fllone cnoHr?* coiu^ 
ploTDont dovinticn. Quo control tube in made irilh 
salt «o1u1iuti iiL^tead ui Htriim to fiee if anttg^n 
alone uUl biod eoitiplement. Another control may 
be inadc with complement, human »eruin to be 
lejtted and ctrpRSol^ to exolude hemolvAina for 
siieep'fi corpiiseleiN Iwing prewint in the human 
aenun. Aflcr iiicubution of the unti^n, eoinple- 
mtnt, «0rum nki:cturf« nnd control lubtit for odc 
iiour. Urn heiJi[iI_viii' hyi«Eem, eoiibtntiDg of t«o 
unila of hemolytic nrnbiK^ptor nnd 1 c-c. cf ^t per 
cent, corpnoc!? SLie|>pnHion, is ndded to each tnb^. 
After a vecond incubation of one botir the iuhi^H 
art examioed for li«n:ioltirh. TJicte should be no 
h«mol>ftiB In the positive control inbf. In the 
otiicr control Inbc^ fx>tnplctc hemolysis !*houlJ hu^e 
taken place. If hcmolyaa Ia pri^nt in the tube 
Cfudaininjf the tnt snxliire tia* miction la nega- 

txrecTioy lyo /jrncy/rr. 

W* *** r lata k m 


tm, tfctiiiutbmMiwcndoM^.tTPlMtift- U 
bCBAlTtii b aUat m b At pMitm «oahikl tiAe 
Ibv miction ta cJ Mra c to rirtic taf vrplntiL 

VtnoM tsodtAcatiow •£ tiiia tecfank h«vt b«cB 
uid b| diffcTtnt €xpinnMitoi« wiUi godd nvsKn 
Xogtirhi, ffir iiHtBMc, hi* oimI hvmui Uood n»- 
peiwocis vHb Ibcir amboRptor taeffftd of ttop'a 
blood. iW pQrpoM btiaf t9 ««oid eoaa^befttioat 
dmt to beuoljrriB* to »bM|/t evrpwdM forod 
oerMOMny ia hvamu wtnm. It W Wen fodnd 
UiAt A Ur^cr nsnibcr of pontJTc ratctioOA in 
f^phllia c«ji be obttioed br oainf noo-bMtod 
•emu of tbc sufftrrtod pstMvL It ia abo fouo^ 
bovtrtr, that a lar^r munbcr of Di>nn«1 ioftctiTC 
wnnni naci u pc^itivee; tike i^ctioa it tb«r«ri>r> 
no4 fo i^Msdfir m% vbtni Ibe hnted wnai b ctcil, 
STtithcliciJ aati^u cooapOAcd of muturea of 
Hpoid bodieo of kaovn ««>mpo«ilioti, bav« b«en «i«4 
with varyiog dcgmft of 

Tbc Watfertnaan teacUoo Baa proved to be of 
^mt ia]n« In 1l^ diagmwifl of cj^ilu. TtM par- 
ccnUgr uf pnHilivr rrMciion« foximS in the variona 
itafi«c of avphilii rarioe with liw techotc of Aifltr- 
vui obmtven. The followiag table ic ma^^ fron 
a «oUeetioB of pcrtcnta^ bj IVarc^: 

Bucecrn-Mv ph««bc a f <at> 

rrt»«T ■jiawB nzs at^ 

t i ci i n ^iT jyia^w* in n 

TiwttOTijfaillk,.-,. m « 

B>riy IMAM «rtUmt 7g -J 

L*i» uerfci irtittiiu. ..,*,„, ,,^,_ ff ^ 

nrnnaratr vrcikllu .,_. .,,,,,, "^j^ u 

Tbe perraiUs« of frntt* in whidi s^pfailii toul^ 
bt •tdwW « f.r at po»ibk from hintorr and 

WA8fl^RVAS\' I{K.iCTlO\. 


li^^Blive olinknl >yiiij>tom\. anil uliKb gave & 
poflitive rtaenoii, vuiif- fron* 0,3 Iji 3.0 prr iriit- 
Thc tcsulU in the paroByphilttic itieoaaea are as 
folLowB: In t»hvpy tiding blooii «cruin, the uverji;;i: 
of poaitive reactiitUTV in G;i.88 jjer oe:jt. ; iibmg 
cerebrospinal Huid. J^d.^ per cent in jzcncrnl 
p&rdds, miug blood fcrimi^ 88^1 jier cent, of cn&» 
ore iKJ^itiye, with ccrcbriwpiiiftl fluid flO per cent. 

The carllt^st appeaiance ot tli* Wswermann r«»- 
Action is thjit tT^porUil by l^wftr^ eight i!n/B aft«t 
txpoaare^ The rcactioQ usually oppcrurs by ih« 
tnd of Ihf fourtli wt*pk afUr iho apiH--hrau[.'e of Iht 

Amoiix DOU syphiUUc diaciuos tlic Wafi^rciauii 
irnrlion hn* b'*r-n oh<rrvrH in trypnn worn ins in^ in 
liTprcwj vitli Ie»4 coriHlanov, jd iicartet fever (aau' 
iilly u'onkiv po^iEivc nnd Irnimit-nt|, w frambofiA, 
tub^rcuIofiiA and ravciTiuraft, In the.N^ nun-^>'ph' 
ilitic di!€a«c3^ the :>nc^ gi^iiLg the hiKbcvt per 
ccuU pOHilivo rcscttooa aro ChOBc leoHt Ukelj to be 
uuufiitui! Willi *yphtlis. Tlw? rtafUtiti* found ml 
time» in earcinnma and tuberL-uloAis luay be due 
to concurrent ivphilia, 

^jKH-thr ttf^atmr^nt ha* hfc^n fmjrd hy all ob- 
s^nvre to have a profound influcnee on the 
WAWffmAitn reaction ami diAappoarance of the 
tat has been obf«r\e<l aft«r (reatmerkt for frum 
flix montliH to fivo ^^cartt. 

A positive KtflctioQ ie therefore rcj^arded by 
iDBuy oWrverd na an UnVu'nilon for further 



FoilowinK the discoTery of immune hemohito 
«eruriji il was a ahort etep lo ^xp^nmcntJi which 
iiivMvf'r] immiinicfttion Willi virions other Umuc 
cells, and as a result of such vork wc nre to-dftv 
familiftr vriih antiwruma for almost every orgius 
of tlic bo»1y, 

MotcliDikotf ffavo the Dame of <^<>t<uin* to tho« 
KfrrumK whiel) ileMtnir t'^lltf oilier tlian tiaciprin 
ftnd cT?throc_vtca , the won! crtolymti i« used tyn- 
or>>Tnowely. Xalurally ft serum which totroy* luiy 
rell wlmttfu-irer in (rvloUnit', but a(x.xjniuig Lo tie 
r»Jhcr loo« ciwtom vhich picwU, we sf>€a)c of 
bnctenol^slne. h^moTyelM and «th«r cytolysinv, In- 
cluding Amozij? the latter *cTnmB whicb destrov 
Itucoc^icf, the ccllfl of the IiTcr, kidocy imd other 

CYtotoiJD? ore of ^nt«rt!«t. not only b«ca(ise tlify 
iiiii«T «' ar« prodticod id accerduiM with tbe ^oaeitl 
ci.t.i.m>».. j^^^ ^^ ftnti-b<Kjy fornnHoo. but they \uit, in «d- 
ditkwt^ a r^rlaiD thmreti^l aDi! portiapa prteticttl 
ittiporiUK*. Imvodklcty on 1h<ir dbcov^ the 
poMibUily bonme Bnauifad tliat ^tff mUit be 
QtiliMd in tbtt diMudAtm of certain phynob^ 
and p4tbo1ocie pioUfimfL For eiampV, hr pnl- 
ttaf tilt O^vM out of fanctioo thr^ti^ in* 
}«ctioiM of thyrotoxic aeruv H m^t hp pot* 
siUo to ooBfim. or i* prore incorroct, cer- 
tain thron«e as to Iho wlo of the gUnd in 
vwtmholjant Or, by the art^tit* d^ctmetion o( ■ 
fnri* T«ncf-nuB« itt n^racnlm pmen 


aPFClt'tClTt OF CYTOlOXiya. 


nri^t be Icaniei]. Tbc 1100 of an ontipancrcatic 
MTum mij^ht throw «c»m« light od tlie nature of 
diabvtwp TherapciiUc pns«ilii1ILR*4 utso siiggestci] 
Ih^mMlTes, One mi^ht be ablo by tneauB of artiti- 
cinl anticrtotoxic norumii to counloroet cjtctoxln* 
vliich were being formed paLhologically in the 
body. Or, by iajectiuff small amouDte of a oyto- 
toxin, prrhftps onn ronld KttmtiUtc lo n r«iewG<l 
produetion nf Uie bomolo^ous c^lls : small doses of 
A hcmolytia [:<jrura mi^ht ho umful in combating 
Anrtninn. Or ktmilII nniniinfjt r»f Icucofu^iir- sr^ruin 
might cauae an io^^rejue in Uie number of leuco- 
cyte*, and thereby an increaj:od rotListance to infec- 
lioij. r<'r)iHpfl aijl'X-y*ofonin>4 aro farmed in some 
swch inftimer as the following: An extraneous 
foxio wibiilflnon oaugou tJio il<?ntruPtion of a few 
kidney cella, the cnnstitiieittA of tbe latter reach 
the cirpuUtion unci stimtilate other or;:Jin« to the 
formation of mctonophrotoiric arabocpptt>r«. which 
th*n a^at in the deatruption of more renal titnie, 
with the mult that a vicious cyek ta »et tip. 

Tn »pit« of 00 vnkny theoretical valne*. the fttndy 
of evtotoxic [^erums hufl not yirjdi-d llic nanltfl 
which were antinpntc'd, ppphaps clucfly bccanao of 
Ihelr lack of upeoifleity (PearM and otbe«), Al- 
Iboaj^h the cell* of the diffcrcrt orzin» differ wJdr- 
1y in their morphology and funi^tion, there aro no 
doabt rirtnin chcmiral coitMtiiiitMiU (n-<.v.'plo») 
vliich they poaMsi in common. Of this 'wc have 
expcnmenlal proof from the f^ct that immnniia- 
tinrn with nn^- t>-pp rtf fp\] pp\^K a «mm which is 
toxic for the colls of various organs. It ia difficult 
or Impossible to injnr^ nrr orpin lo Ihn ndtiBion 
of all others by meona of a cytoloxin. Ore may 
attempt to purify a ejlotoiie Bcrum tbrongh ab- 

E94 fXrKCTiOK AlfD iUVniStTY. 

eorpliou of the ad^^entitioutf aioboccplora hy imAiit 
of the oorretponding cclU, In&»nuoh, hovovor, ai 
Ihe wfiult U II dc*rea«e in the cii'iet ainbooepton 
AA veil AB of tlie £idv«uLiUoiiH, the desirgd oLj^ct U 
not fully rcaiiJtcd. Thoorrtieolly thp cytotoxic 
IreetuiQnt cf mali^ant tum^ra ofFen an import 
taut field for reaearch. Hut here, too, vanoiia dif- 
ficultir^ arc involvc^ij tui Inck of jtpccificity of 
■eruiriD and the multipUcritv of cell-typM vvblob 
Gflnfltitiito rlilTermit tumors 
n«^ftmtiBA. EAperiuic^nfi^ willi cytoti^xicwrums mavlff^coA* 

'llti/'AiiKSl <luctc(! in I'virc or in the living nnimiil. In ciUict 
case a. nocosaary condition lor the roeoj^nition Of 
tlifl rytntoTif at^tinr i» the prtwcnrp of Aom? di»' 
tinctirff ii^ nf vitality on the part of tlie cell, the 
loBs of which may bo takon a« pvidcnco of cell- 
dp-ftth. LoK* nf motility and nf proUfrTiitivi? powi*T 
indtcAte the death of bacteria, and eolEition of 
hemoglobin tho death of erythrocyte*. Under par- 
t](?uUr condltfona )i»a of motility on Ui6 part of 
certain imav cclh. && gpcmiatozoa, Icucocytos ao^ 
ciliated cpitholiurn, in an evidence of cdl death or 
cell injury. Tlie toik action of serums on cell* of 
flxfld form ir mnre difTKriilt fo determine, and for 
evidence one niuat rely on such pointa aa cleariDg 
of the protoflnam (digojtion?), ewolijng of the 
cell and iineleiis, actual solul.iuxi of Liu? (^yLTjplaam. 
or degencmtiona of the homologous orgin* when 
the Bertm» is injocted inic the Hviiig animal. 
The tpc!»iic of immiLni2fltion vni\i tissue cells U 

in.iiiii>.(<«iiA« dniitar to that cf immunization vith bacteria- In 
order to obtitin leocorytoa in abundance), artificial 
IfiiroL'vtnsi* is produced itj I he peritoneal or pleural 
cavity by the injection of bcuiUoTi. or lymph 

'icf'iiDir or 





glauiU, K[j]ctfn i>r bone-iuarrow itm^ be grounil up 
and iDJcctod. 

ImmiLcuuiLion wiUi solid ^rgonB, tA Uvor^ Icidnej 
or testit^e. is easJIjr accomplUbed, a iiecefisary pre* 
Jimicarj lor lajcction bemg a tJiorough diBintegrd- 
tiOD of Uie tissue by g^Hndiug wjth alerihj aand; 
the mntlting iim»« whi^rt 6u#p(-(u]eJ ill salt snliitirjTi 
|)ftae€fi tiirougb U^c lujccting nt^edlo readily. 

Cytotoxins^ like bftcrteriolyBins and hemolystnSj 4min,ff(*,nui«, 
tie complex BubsUucc-R, hi Umt tbej coo«iflt of ani- iliyi^^i^^ji 
boceptors mid comply Trent, p. The nmboccptoTv 
niane are intrrenfind diiriiijf immuni^atior, th? com- 
plement bdag & normal constituent uf tl]« ^eruin 
of the animnl, I'hc phonomona of inactivation 
snd reactivation aro oLspr^able here aa Id coonec- 
tioQ vilh otbcr cytolytic wrum-i. An tic jto toxins 
are z^dily prodnoed by immunisation vith many 
eytotoxiria; tlie njitiKenirn THually consists of anti- 
complement, bnt in some inrtances nntiomfcocep* 
tcrthave bf^n d«Bcribed. 

9iniu1taurH>ii>dy, or m^rly ki>, Tjini]sipini?r in •»*r"i»i««i»« 
Tunna and Mdchnihoff in Paris rq>ortcd the 
production of Bpcrmotoxlc aeruma by immuniza- 
lion witli HprrmatoxoA, ihr nnti.Tal maLillty of 
which rendered tbo recognition of coll d€ith tstjt 
The l^hnie which TjnndftUiDer ftrat employed waa 
Umt of the P/eifTtr ciptriment in Ibat ho immun* 
ijod jpuncn pieft with the fpcrmatoMft of oattio and 
ob»rv«d lo«a <if motility on the part nf thn coII» 
when tbfy were injected into the peritoneal carity 
of the immnniirad animal^;. Comparable irith 
many other cytotoxliB. ffp^r:notoTiti killfl thr* bo- 
moloiroUA cell without causing lis eoltition. The 
loss of motility h alno ob?*>rred in bun^n^^rop 
preparaMona provided n frenh or a complemented 

iXFtcrtoy sxD lyuvstjr. 

Mnuii ia afi«d. Most CH>nnAl vmttiu ahow m 
(TCater or kn ikgrce of Uxic action for the spcr* 
matosot of otbor animal^ and normal ipormotoi- 
ina like the Imoiiitie oonaitt o/ n^nboccptar and 
complcmcttt- ^fctc^nikDlfT cUiins to }iavc pro- 
duct an autoeperraotoxin by immuDiziiig guinea- 
p'lgt wiUi the apermatoroa of other guineji^pigSn 

When a. npc:rmAtoxic jcrum is injected into tho 
living aninia] it is thought that the amboeeptJ^rs 
arw tftken up by tim hoitLohj^tms celle, and thia 
noxtld Accm to affect the Titalitj of the aperma- 
tanan. itifismw^h u De Leali*? r^dcrcd male fni« 
•t«ilt* tor IC to 20 davBi liy the iTijection of tha 

It ia of thporeti<^al Interest that rastrat^ ani* 
mala will yield sperm o toxin by inimimizatioQ* 
diovin^ tliat tlift nmbocfrptor^ nrr rot of nooouitity 
protliicwl by the GnalogoLiH tissue of tb? immiiii* 
iBod animal. From the fact that spermotoxic 
•entma are hemolytic, it ia aafumcd that certain 
wccptoni arc common to errtlirfxrytcs and qiernia- 
loioa. Hemolytic eentrna^ on the other hand, may 
Ntit br spcinwloxio. Tb«rc in uAtbin;; rontmdfc- 
lory in thia lack of rcciprccal action, for tlioae n^ 
ooptora vhlch ara common to the two eella may not 
\if important for Iho Kfe of th«> ^jwnnatonion, 
>vhor«Aft Iho Qpi^Qstte condition prcraila with tlio 

It ia wrtainly of inlcrcat that Emmvnintion wiih 
ihm plaama of nta eauar* tha formation of apcrmo- 
loitc anttooopton. a fact nrhif^ pokiti to certain 
eowinoH ownatitvwntff of th^ tvo calk 

AntianarnMlQiln may b« prodiKwd bY fmnuum- 
lion with vpartiiotftxfa aenuu (antmmplemMt or 



Following tcchnic «imilar to that omplojod hy txuruiia 
ImiitlBteioer. von Dungern i»btAln&3 u cj-totoiic KpuViili ".'«,'! 
ftcnun for cilinW cpiUicImm nf the trnchcfl- The 
colU difiiiitegTBted in tlj« periloncal cavity of th« 
immuniKiH} animal, hut uot m that «f the normal 
imiinaJ. This scrum ulao proved to he hemolytic 
in epilo of tl]e fact that no erytlirocvtea were in- 
cludwl in (he iujections, Thnt llie ra^eptora whidi 
charackriso ciliated epithelium arc widely ciistnb- 
ut6d ia ahovm by the fact that ImmunlEatlon with 
cow*« milk cauwM the foriualion of a cytolytic 
acrum for the trachcat epitholhim of the cow, 

Tjeucotoxlf, lyniphotoxic or lymphttotoiic 
scrums arc prepared by immunization witli ex- 
udate which are rich in leucocytea- or with th< 
rmulHinnH of lyinplinid nrpm=: lympK ([Inmlit 
spleen, bone marrow. Htlchnikoff prepared the 
Ihrt aenim of thlJ nature Ly the injection of tlie 
eplcrii of rat* into jciiinpn-pi^, Tjeucotwc wnimti 
are toxie. not only for leiicocytee, but also for red 
eorpuaoloa anil endothf»lial celb. When injedwl 
inio the peritoneal cavity Lhe endothcliiJra is 
Ihtovo oif, and when pytn euhcutanooualy the 
capillary i-mlotlinlinm ie attnrkpil, with th^ rp«ult 
thai hlood eseapea to form a largo hematoma. The 
act]r>n of the flenim on leucoeytM may be ohflorved 
in vitro. Thi^ mononnrlPRr w*!!* arp *tftnn nmrr 
aujKYptihle thoji t}te polymorphouucleara, allhoui^h 
tbu dapenrlfl iiomrwhat on the animals and the 
partfcular or^an ti*ierl ft^r immimf/afion. Theeella 
Ictto their m'^tilily, th« cytop!n*m b^^comea trana- 
parcnt^ and swells to form a largo clflar voncta, 
vhirh nppeara to be Hurrorind^ hy a aharp. thin 
membrane. The cetl content* niay be rli^ehnrffwl 
OT entirely Ii<jn*fl*3. th& midens alone being r*e- 



BItf Ab«, 


Boh til an ||*~ 

DgiKi2al>le. Leucocytes «r« ag^lutiiuted bj the 
BBRtm, A 8tr<»iig Lmcotonc scrttm mdy Im faUl 
fo the anitnal vli^n iiijBct«d iato the peritoneil 
entity or blood strcftm^ the exAct cftuse ol death 
b^icg ob«CQre. 

Metdi[]ikolT, Iftking ILa vlfv that Uie phenom- 
ena of old Age depend on the destruction of vort' 
ous liesud cell* bj the mononuclear leucoc^vtra 
(mju.'n>plta£ea), eiprBsGcd Uie bope that a ljiii|»bo- 
toxic icrum might be utili^ to combat the Action 
of th«ee cell? with the rwult ttiat life- wouM be 
prolonged. Wlictlifr or not hb view oa to the 
cau«o of old itge is cor?«it, bi« plan of Antagonizing 
\i had to be abamfoned becaiise lencotoxlc seninm 
do not inJQre tbe mncropliages to tbe exclusion of 
ctbw lencocyt*«. 

Tlie injection of n \tfin^iiaxic serum into the per- 
itoDcnl cavity of a eruinca'pi^ coii5e« a temporflrj 
d«rreajre in the number of teucooytefi, find during 
Lhin |»tkk1 of bvpoli'Ui'm-ytoHis tbu re«istnoce of tbe 
nnimn] to pcritoncnl infections with the oi^oniamt 
of typhoid and oholera S« lowered. One may refer 
tbifl effect to tbe dc!«trucf.i\v oction of tlie Mrnm 
on the leuooiQlce, by which pbagocytoaia ie pre- 
Tented, «r, aeccTdin^ to WjM*cjTnBnn, it may de- 
pend on tbe action of anticomplcment which the 
leuootoxic serum contains. (Leucocytes contain 
complement, herce immunization with leiicoeytM 
eeuice tbr formation of onticomplement.) It ifl 
probable that both fflctora a» of influenoo, Tn the 
f?our*p of frQm Lweuiyfuiir in fortv-eiplJit hour* 
itiU^r pcriboncul injodion of the ecnim. the Itraco- 
oytea reacciimnlate to an enormous extent. Dur- 
bi;c thi* Kt'tjndary In perlt'Utcic.viosis re^istnnre to 
perilim^ oholorn or t}pboid ie increased. Some 




non-toxic sijbst«ncc», lu bouillon, have n aimiiAr 
t;lT«ct, and although the b«ocii{1fln leucocytosh is 
netrr an grmt ns tli/it (.-autiL-il by tbi: Itiuootoxic 
eeruui, the prolcclive action ia eqi'flUy high. It 
vould mwm that, knoooyte for leucocjt*, thoso 
whR'Ii acc^ufniilati^ following the injeclicm of lonco- 
cjloxic Mnim ore kes cfftc'wnt in uniibactorial 
Action thiui Ihostf whose prewnop ia rniinoil by 
noiitoik- aubatances (RkktttJ)- Heme there pj-oh- 
ebly ia no field for IcncoEoxic Rcrum o^ a meana of 
temporarily inrreasing rfwiBtAiico to bacterial in- 

By guardofl immunisaticn Bcerodks obtained an 
intileucolojic semni. 

NephrotnKit^ ^aumt have been brought into 
clo*c rclfttionahip with chmcal and anatoTTiic prol)- 
Ifltns by a niirnber of investigators. Some iiormnl 
aenima are lield to be nephrotoxic inaamuch as 
thoir injection is followed by nlbummuria njtd 
]*enal fl^genCTaliona. Immnnp npphrotoxinw bsvA 
ft ■imilar but more pronounced ^ei:i. ami Lindc^ 
man refflJTGfl tho death of his erp^rimcnt animals 
to the HevelopmeDt of a uremic oooflitlon. Of 
moTt than cidinnry intcrcAt u t)ic dnim of ncr- 
tain workprg Ih^l sutonepbrotoxins may be formsd A«<iB*iitiiHi* 
in tl* liody. Oil** (T^nilt-muit) rauHPil a toxic 
ncphritin in do^ by the injection of potflwiiim- 
bichromate. The wmm of this ^oi-. allhoujfh free 
from c?iTomio aci^l, Mvnn toxii- for othpr do)^, pro- 
ducing: th^' j^f-mptoms which ar*j catjsc'l by on im- 
mnne n^hrotoxif? aemm. It wa^ supposed that 
the chromic adrl in the frtt doc cnuncd (?]*intcKTa' 
t)on of Ttnsl cells And that the constitucnla of the 
falter vere th^ti Inken uji bv ntrphroloxic nK«ptan 
which nonnally reeide in the organs of the ani- 



/>T£cnf>A JtXD tMMVhnr, 



ma\; M a r«ult iW rw>^plort were dverproduo^ 
ocd their prcwDcc L^camc m»;ijf(4t when ih« 
iemm vr&s iujocted inlo other dogiv In ac^rJ- 
fluio^ with thin vi^v thf orij^nul ti>xi<t (tauw; of & 
dfigooerattve nephritia would he of Icse cooec- 
qiioncc fnr the continunncc of tho condition than 
Ujb formation of (Vie iiGpliratoiicanitiocrplor*; i, c-, 
tho format ion of an nutonophrotoxin. 

Somowhftt airnilnr roAult* vera obtainod 5y <>th* 
er» IhitfUgh li^atiuu of tlie reuaJ vein or arter/ on 
ODO tide* Oocutitucnt* of cclln of tho idotaU<l kid- 
ney wero euppoflod to bo ab&orbc^, and na n conn^ 
quenc« nephrotoxic amboceptors were produced in 
oxccM by CT^nns of uncertain identity. To the 
aedon of tho new-formefl bodlee were nttrihiitpd 
tho dogcnoTntiTv chATLjEca which vrcrc found m the 
oppoeito kiiincy, and thi? tiophroloxic pToperUa 
which the Aernni inanifeeftted whon injected into a 
h(*AUhy animal of the Mme irpfciof- 

Ac(*ortiing to Ancoli an^ Figan tmllatoral neph- 
nvtomy =v injiirw Uu- upfiuAilt.' kidney (uvt^rwork) 
thrtt the M^nim of iUe uniniaL hccomca nephrotoxic, 
Thnv Mnte aIvo thnt an ntiimal . the i^mm of vhi«1i 
cfonUiiis n^ptirotoxin. may antacomce tlic latter 
by Iho production of untin^phTotoxin, and Jcaggcot 
tltnt upmilAnnnMii nvor^rr f^^rn n^phritia may be 
duolothoadiooolnohanaiitilMMly. Tbcyvould 
iCMimt f4r tho oardiM hjpcTtre^y of n^phritia 
by Um Mtiui ttf b^brotoxie aanui Id cuniflg ooe- 
tnolioii «t tlio pMiphffal rmmh vitt tmtipuak 
liKTiNwt r>f hhxtd pTfwnw: and for Iha n i r ma 
iyiik|bt««i« on tW Wit tfcat tl» vcnun cttataiika ■ 
iH«HM<ktie cwiititvaMt 

W» Wdly 4ar* comMit mil tkMwAI^ 
flwki* it iliv4ai*« mill lli«y k*t« 

oraicx vYToivsts/s. 


confirmed. Yet whafeAer iiia^ lie ihtn real valae 
they 8CrT9 to emphasise the posfflbility that thOM 
principles which are ao imporUnt iu rdntion (u 
imtntiiiity against infectious iliaeuAtu, may be 
equaliy Lmp(^rt&nt in reUtioti to cbhcr pathologio 

Hepatoicxiiis have been obtjiiued by u number 
uf workers, and the aJtonipt line been made to pro- 
duce autohepatotojins by injecting liver tiseae ot 
the guincA-pig Into animda of the snme apeciee. 
'fhc ttucccAa was not unqualified. HepatotoJCiM 
when injected arc reporlPfl to ctmsQ insular degen- 
entiens of the ti^er; Ijowever, tlic lesions may be 
attiMd, in part at UosI, by capillary emboli of en- 
^otTiellfll cvik or crytlirocytcK. 

Xcurotoiic seiums Eiavc been studied with «omc 
tJiomu^fhnnai, Whether oni* injects the cerebrum, 
cerebellum or spinal eord. the resulting perums 
apparently are sirailar; either an anticerebrfll or 
an Antie«roMlar eerum will enuse do^nerolionN 
of the apinul *;aikglion ctA\g. In \ii:w of their 
brand ran^ of fict]{>n it r.ccma imprab^iblc that 
neurocoTic wmmK will b*^ of nervier in Hearing up 
the etioloi^' of ft/*tein degene fat iocs of the nervous 
tracCa. Thty are equally hcmelytie and hemofr- 
ghitinating and rnay also V endnthpliotniir nnrl 
lencotoxic, When mJicd witJi emnlaiona of the 
homologona brain tissue the neurotoxic omboeop* 
tors are boiiTtd hj the receptcra of the nervous tJft- 
nie, and the acntm confcqucntly loses its toxicity. 
Antineiirotoxic aerumB hav& been described. 

Syni-ytiolyam U tlit name j^lrvn lo a lU-Tum which 
ts obtained bv immunisation with the placenta. 
Cerfain writer* fVeit and Scholten, Chtirln and 
7>Taniare) report that the injection of placentsr 

>f nmlnviH^ 

lH<|«in III 




ItcnM alone causes albinninoria, a <vMi8idoraCion 
which IckI tlinn t» ftft«iinic that th^ pUc«ntar d^lU 
oontftin a iicphrvjtoxic mbetArtcfr, Tnn^mcjc^h ns 
placefitar cclU or their convtitttcntft mty reach the 
oirculaticm daring edampua (Schmorl) it voa 
iiat ff long sUp to BUppoe« that the n^bHtiA of 
projiriAnc}' ie ihic to the lo:iic syncytial cell* which 
rtro obflorbcjd. The resuUs which Weichanlt re- 
portfx) gave eomo etrODgth to the view juet cited. 
By tn-nliiig plnrentar tiwtie of rabhils with th^ 
*prc;fic cvncytiolysin the toiin 8Hppow?<ll\ was lib* 
crated, nnd the Trnna when injected into normal 
rabbits i» said to have produced «vinptoin» of an 
Mnmptic tiRtxtrp. On the basis of these ob^prva- 
tiona the hope ho? hcco expressed that an nnti* 
torn for cclmrapaia mi^t b« prepared by imniui- 
iialioi^ with pTacentar ti«siio. ITov&TOr, the «wi* 
ditioiLS are bv uq mriui-i xiirpic; luiy vmltirr which 
tlitt deetruction of ctrcii!atiDg ayncvtial oelle or 
thviT UoAn vrould afford tnigbt be more than oftnt 
hjr Uw action of tli« heruotoiva mod cetirotoxiD 
wlucti tfct emu ta aiid to €OBteiiL Vbitfcv or 
mat tlie hjpetlMtkil toxin ol §jMw6al edb uy 
btt vparatcKl from the oUwr cetl constitneati^ nid 
«lk«th«ir imvi«uiatiofi vilh &e toxin will yMd 
ii uitttodo Mnm om poarihitttSw wMdi T«nattiB 
ht fUite breittptioii; tbe mnlta ett«d baw 
iwtfcaaii ebOiaeA ty nil obear^er B. 

LifyiMHB hopM lor a amm-Jia^noofi of p c^> 
navcT. It. aa a nf f awd , Ite blood of o pngDOBl 
wQM4n c^;tllU^M ^cy mtM eatta «r iMr protela 
ot dMMnti««, th* aim vfcm wivd vitib 
o a^acw i^TfttjrtiitvibK iB«y eoMt o ptaayttoJa. 
He Mim H Uw J Nwwat T on a te ataaMo wt 

tfVCLHOi'iiOTKJD SUlWyiZJ^riOX. 303 

plftcentnr constituenU in the pirciitntion by this 
biologic method. 

Antithyroid serum is prepared by immuniwi- Th7«tft«i( 
tion with ground-up thyroid tissue or vilh extracts 
ot the organ- It la hsniolytjc, «Ten ilimi^h all the 
hlood has been washed from the tissue which was 
injecteiT, Porlis immnnizeil with tht^ "colloid" 
material of the gland obtftiniu^ a hemolytic thyro- 
toric serum. When tnjeetsd into the living animal 
degenerative changes are produced in the thywid, 
und Ewmc authors report the tetjiaic phcnomoTin 
which ofton frjllow mrgical removal of the thyroid. 
In Tery caretul work, however, Portia could not 
produce "tho cxaet picttiro prelected hy thyrodoc- 
fnmiypd unimela" Degenerotiv? ehnnge« were 
found in vhtious organs, ti& liver, Aplecti nod Icid* 

With the idefL of preparlny^ an ftntfgen xvhftdi 
would contain, eo far as po^ihle, only sAibstances 
chftrarieriflltc of vari»*ty of oelU uned^ Bt^be hne 
Hiade iitv nt iimh'uprateidf* nf ynnnxin tijghnft. ewpp- 
cinJIy thyroid elnnri, to prodac« antiserums. His 
refiiltH would in^ionle that In tliU way serum? mav 
bt oMdincdt which nir Kprriflr for dilTpmnt iTiri- 
ctioe of cell* except in hijuh iron central ion. 

With the nv of such a 1hyrot'>!cie s^rtini he hiti 
reported good W'.iultn in ca^cfl of hyperthyroiditiu. 

PeBiro has failed to rontirm thoM reeult^ nnd 
obUiiiH rexTilU, with n^MiMeoprot^id aa antigen, 
whicli arc similar to those which }« oltnincd with 
•implo cxtrat^td. 

Heehe, however, eHtieiMH the tei^hcic of Pearcff 
in Ihut Pfircc h^ted hi« pn^parAtion. thus, aeoord- 
inj^ to Bcobe. doftrcyicj* tli« fpocilK biologic chttr- 
JCtCT of th» PTtracH. 


tsFEGTioti d^•D liiMUhin: 




It would Appear tbat. further observatiooe arc 
desirable be-fore i^ondmtiou* cin bt <lniwii rrgsrd- 
inji: the laliic of rtuelcoi^ioteid sa uMlgeu. 

Brown Puaoy has mode the interteting eti*r)CC*- 
Ltoii in regnnl tn ayrnptilhrtir ophthalmie thai the 
diecoao may be due to the formation oi autocjto- 
tojcina which are apoeiCc for the cell* of the innor 
siirfnrc of tlic ciliary body and iris. The diatnte* 
^clioD producU of tho eorreeponding cells in the 
eje wiileh wu« primnriiy injured irould constttuto 
the stimuiua to the foriitatiou of the apeeiilc anti- 
bodJtt. T)ic posaibilitjr ia as yet a problematic 

Tl)e experimectal study of cytotoxic Hrruma for 
tho pancrpfls haa, up to the prtscct time, tluown 
liitJf? ligbt on pancreatic diseases. It stated tbat 
the eenim may cause transient glycosuria, and it 
U i^iiid to hove ati nntitryptic action in cxponmecta 
prrforifieil in tJm teKt-glass. 

The r<^^ulbi of different obscn-era conccminie the 
action of antiaeruma for the adrenal gland are not 
ill pnUre nMXjril, Althougli degenerative chaiigH« 
mBy be cauied in tlic gland when the ecriim is in- 
jectodr tho action ia not apeeific; tlie eerum may 
he highly hemolytic [AbboU). 

Goni clainia to have demonstrated In tbc circula- 
tioiL of epileplics a cytotoxm which cituAe» tho efv 
ikpUc attackfi, and leporta the prodiietioo of a 
apcoific aatitonn. 

Wisichardt has puh!iabeil Jespriptions of a toitn 
which ia peculiar io slates of exhaustion, giving 
an account of the sp^iflc antitoxin which he pro- 
duced by inimuniRafion. 

Oilier cytotoiins which Lave been prepared, aa 
tbow for tli« pituitary body, gaatric muooMQ and 



oardioc- musc^l?, have at the present time noUiIng 
more tli&ii general biolo^iofil iiitcrc$t. 

Jt would Bccm that no question in Tclolion to c^Hrcmi-. 
T:jtotoxic serums ia mor^ imporltt&t thiLii the fos- 
sibilitv tliat autocytoloxJiiG muv ilevelt^p juid in- 
stitute tJio vieioua cycle which wos mentioned ear- 
lier. It is true tliRt the rcsnlU of «ome mrestiga- 
tora euggeBt the probability of such & procefis^ but 
it vould be going too far to say tliot its exiBt&ace 
lU an imporfant patliologle law has bwn «8taV 
iifhcd. On the contrary, the dcvcloproCDi o( aut^ 
cytotoxlna is one ot the rarert of occurrences in 
expcHmental work; ftnd I^hrllch haft spokai of 
tho inability of the bo<ly to form such antibodies 
as a eonditioti of "liorror aufotoxicua/' The cells 
of ciur IfuliirvK and our erythrofTvfi** riTrUinly ilo 
clegencratc. and it ia quite poaeible that the reccp- 
lor* Trhleh ato thereby liberated jwtunlly roacJi 
cytotoxic nrnbocoptors which »re eitnatpd in rAhvr 
orsana. In fh<f <*vcnt that the procesa extends to 
thit point, 1[hr)ieh assumes that tho ambocoptor» 
am of a eewile nature, that i[k spite of the atimuta- 
tion tr. whieh the cMIb are subjocteti the "aewile 
ambw^fptorft*' may not he overprodufV'd and liV 
erateil aa in the case of aotibodiea for hactCTtnl 
»nb<tanccs or for the cells of othor apocicv. In 
ficeordanoe villi Ihia explanation we are saved 
from intoKff^ations of th& nature in question be- 
rauf^ of tho ef>a«i]e natiir« of the cytotoxic ambo- 



tor r«rn*keB 


Ae one may learn from llio wriUnga of JtetchtLi- 
koff. fhfljcocyto*i*, in its broad *etifle, cxoTCi«e« 
three distinct fimctiona: nutritional, rworptivt 
naA protective. 

PJiagocytoaia, for purposes of nutrition, ia moit 
highly developed in uTiiccllutuT n.T>ieboid organ* 
lAmA, but is fi>uiid also in aniuiul^ of oooaidarAblt 
crgnnic differentifttioii. It is, pcrliop«> nowhere 
more stritdng ITian among c?artiun myxomycetea, 
vliinh are large, nnlced, imiKiniirli^fnl, pnjti>i»lai- 
mic maaaoft belonging to Uw plant kin^piom, and 
nhich po^csea pectitiar, stow, undulating motility, 
IngGatlon h accoiiipltsheil llirou^h protxiplGumic 
amiB (pscudopodia) which arc thrown out to en- 
velop the object, Mimite plant and animal c^Ils, 
living or dead, are ingialed in this manner hj the 
inyxcm;^cetc8, amebds and oth«r unicellular organ- 
igma and aro eubsf^quently di^rwted by meana of 
intrace]lukr ferments. Tlie fermpnta whii^lj have 
been citrnclcd from s^Mch cells are proteolrtie dncc 
thoy digott gelatin and librin, usiially in an acid 
but vometimeH in nn alkaline milium; that from 
Bmcto hna Vpcn callM amibMii'itflse. In the proe- 
eia of digeatiou a '^vacuole/' aeid in reaction «kI 
containing tlic ferment, forms around the in- 
gfstei3 particle. In certain phoeocrtic unicellular 
orgnnicjufl the pwitoplaBtn ahows a d^^rree of ^ifTer- 
entintion, a mouth and an anna beiitg ^imulntnl nt 
points vh^re tJie food ia most readily taken in and 
dlBchargiKl. Instance ar« nt«d in which ameboid 



or;ganiam£ protect tliomscivcf oguiiist inimical colU 
bjr mating, killing, and Unatly discbnrgrrg or 
digesting flie latter. 

Thp boinnisl:, Pfriffrr, flrflt: (lennribpil Ihe plus ckcBaimtu. 
nomeoa of cegaiive aud positive chemotaxia in re- 
lation to the myxomywtcB. Under cerlain condU 
*ion» tbfty either are attra^twi tnward or move 
from moiflt place*, Thnt n negatiT^ cbemotaxU 
may l>e ohaaged into a positive vne shown in rela- 
tion to salt solutiona Whsn pl^sd id the Tic-inity 
of or in contnct with Bt.roTig solutions the cell re- 
cedes, whoreaa if otjo pnsace gra<Jwal)>' froin wealtcr 
to slronj^?r sjilutions the latter evenlitally attraiH 
rathor than repel the celL 

A* one gops higher in the ui;imaT scale iillrattJ- 
luUr digcation for purposes of nntrition is cod- 
Boed to rather deiinite groups of celts- The intce- 
tintl epithdium of certain invertehratee consists 
of "ecsaik! plingtM-ytps/' rclla which, indiviJunlly 
or after fLision into plasmodtal ma«flee, aurroun^ 
flml digest wiHd partieles of food, R is suid thnt 
in spongce the digcsHvo tract i^ not aliarply sepa- 
rated from the rneeodermal tissue, and the cells of 
th» latter *1iar».* with the former the function of 
intracellular digestion. 

In higher inrertebratea And Id all Tertcljrates 
t}ie inteelinal epithelium ocflace lo ho esaontially 
phagocytic, digestion heing aooompliahed rather by 
fanncilta which have hvttw Ki-crcteil by the intestinal 
and related jflukdular cpithclinm. 8uch animala, 
revcrtheleM. poii oa an abnnJanco of phagocytic 
cells, bnt they are in the main nieHoIilmvlii: in nn* 
ttire, and may have nothing: more than a remote 
T«fation«hip to the nutrition of the organivm. 






Mt'b^hnikviT OiviJts Liie p)i£,goc7tJc cclU of rrr- 
tebralce into tho macrophages and the micro- 
plLag«£. Tlie niaj:rropheg«e or Ui^ phagocym in- 
fliiiln thn iargi- IvmjihcM^ytcs, eriJollieU*! celb*, 
nmeboid c&nnectiTe ii»UG cells and others which 
may occwioniilly take up for^i'j^ partiplc*. Our 
[lolyrnorplioiiudear Imicocytea are the micro- 
pliairea- Jn relation to immtmity wc arf: concern^ 
chiefly with the large lymphocyfea {macrophage), 
find the polymorph oniielpflT leucocyt-ts (micro- 
phagc*). Although £itch cella may coaiam many 
fiH'montiL. MctchnikoJI recognizes but one type iii 
reTfttioTi to their rpsorpjive', <ligagtive and bacteri- 
cidal actirities. Tliia he calls cytaae and dJjtin- 
jniielice tliat oE tho macrophage aa macrocytasQ and 
thjit of t,hc» micropJinge as micrncytafie. CytBnii 
corrwpoufis to the complement of Ehrlich. The 
tvo ecllfl dci not havo idcnticnl activities, tho ma- 
crojdiajfe being concerned spft^iaJIy In the r^orp^ 
liuij of iiKsiie cell]* am! in immunity 1o certain 
chronic diacasca. as tuberculosis and loproay. 
whoreaa the micropliftf^c ia tho cell which ie oon- 
spicnoitMy snltnierohie in relation to ai^tito tnfoc* 

AceorOiwg to MetchuikolT, Uie leucocytea are 
very active in the resorption of uaelc^a or foreign 
cells. J^urir^ the metamorphosis of certain in- 
vertebmtra it is said that the Inrvii] tissiuii nrit 
r^nglobed and djgrsl^l by vranileriTig phfe* 
gocytic cclla» In involution of the utcrui 
the muscular- tissue is invaded by leuco- 
cytes irhich laXe u|j ajid tW^^i or carry away thL 
''retrogrewivc elements," Metcfinilfoff's concep- 
tion of eertftin atro])}iic procowe*, particularly 


U^oe^ which aro j*n>upcd among the senile atro- 
phia, in of lut^rttt to patliologtaisu In eclrrN.ic 
fttropliy of the oTarics tLe large l^-mphoo'tCB in- 
vndc the tiuiic, turrouud uiid Jeatroy the ova and 
follicular epithelium an<1 eventnnllv. as fibroblasts, 
participate in the formotion of fibrous tiMue wlkh 
10 a liogreo i* aubatituW tot %ho ori^nal etrno- 
txin. In oil] iitiliTidnftts or in 1l]oi« of failing 
moiUUty it ia aatd Ujat gacgliooic cella are foUDd 
in n iTTcfitcr or loss rfcjfr^sc of atrophy hocaucc of 
tlie fiction of certain moDonttolear phagocyt?« 
{netirDTopiiagwi) which are contigiioiis to or form 
a ftonc around the cell. The ncuronophacefl may 
repc^Mmt niononnclpar nelU from the hloo-l or 
Uioite of pnvlifi-niK'i] n4?urog]iij,r tiw4iJi!, Tht! bettt 
«xaniplc« of thia condition were found in very old 
dogr The diromophor« of the akin, according lo 
M^hnikotT, may be ccft»^ii1ered as chromophagee. 
Whether or not they arc of rpithclittl origin, aa he 
elaima, th^ are SAid to eiiat normally in the haira 
in a latent or innL'fjv<^ conilition. Aa old a^ come* 
on. or as a result of ether obacnre c«utic*, their 
attitndc bceomo« An ac?tive one, and they proee«d 
to take lip and di^Ht the normal pignienta of the 
haira. Hrnfc, white hairs are the Temlt of an 
autoponiflitiam by certain monorudcnr pha^* 
cytM. In muscular atrophy it it held that the 
sarooplaam takca up the strfAte<1 liasue afler the 
manner of phn^oc^tca. 

We come into closor touch with our i^ooorfll 0ab- 
jecl ef imrannity when ve consider the resorptivo 
function of the phrtgoeytw* for *>elU which ar** for- 
rign to the host, for r^xamplp, (owarJ crylliroc>'t» 
whidi are injorl^l for the pwrpofc of predncioff a 

IKK «r ii« 



n'fgcTiOjr A3!D iMuvyirr. 

Formal I vi> 
r«f Crt*|DiilHaH 

hfUKilytic mrom. FolEowlag fooH m Injection into 
iht prritoiwal G«niy tlicre occnis ft grnt iccatrion 
of rQACroptftgeo whish i3ff<^ tb« errthroqifv, di«- 
£olve th« hemoglobin &nd er«iitualJf digoet U;« 
stTDUU- The fflcie plmgocyt« are inixilTecl in tlw 
resoi^im of any other ford^ cells of Kolma} on- 
fpsx vthixAk mar b« injeot^d. In tieer of the ictroc«1- 
luUr hecnolTSis by th<^ leuox^'tes, ouc nmj suspect 
that tbc btter contain a hcirtoljtic fciment; oitc 
whieh, perhftpi^ i£ anAlo^tu to the henolj^aln 
(hemolytic aiDbocejiton and cotrtpleinect) of 
MTums. On thU point tlierc hiu been nbLrp dift- 
cuB«ioa. MetchnikoS cit« obsen^tions to ebon 
thai A frrmrnt of thi* nature mny be pxtmctfvl 
from the Ijmpbold organa, that it conUina a bcat- 
fiiuceptiblg constituent, nnd thnt whan frecli it 
ma)' be used to reactivate a beatcd hemolytic 
«erum. ThU vould iiidicnte that tho leucocytes 
contain cyU*e (compUment), but it t* not H<yir 
thni ibey Moold also con(Hiu tbw fijaiora (ambi*' 
oeptCTs). NcTcrtbclcas, tlic demonstration of on 
SDlmloLicocytic hcmolyiin and a knovrMge of the 
phagocytJc power of tlie leutxx^'tes for erythro* 
cytei form fJm bft?i» for MetchnikofT's belief that 
aemuT-bemclvsin is notlunj^ more tlian iatra[<inco- 
rytic hemoljuin, wbirli hthW pnJfUT fnm[3ii[oiii« 
may reach the aerum or plaama, By an eitenaion 
of this concq)tion it is held that all cytolynins are 
prwiiieed by the mficropbages, 

Konwbur and Mor^nrolli, on tlie other hixnd, 
obtninwl from lymphoid and ^rioua other organs, 
not a thcrniolahil'? b^HioIysin, but one which with- 
alands prolonged boiling — ft coetoatnbile hemolysin 
vbich is soluble in sloobol, shows no antboeeptor* 




complctQcnt coiupoaition, and U incapuble of yield- 
ing antihcraolyain by iiumxmiiation. Theae re- 
tullx, MolchnikolT IioMs, ure only in apparent <5im 
cord wilJj tliosc obtained by himecU and his pu- 
pils, imd depend on the methofls of eJttrftction 
which were employed- In order t<» obtftin the ther- 
molflbile hetnolj'fiin uncootaminated witli the ther- 
uiGfitiibile, the extraction mtist br n rupid one. If, 
on the other horid. it la prolonged^ aa MctclmiJtoff 
asaames that of Korfichun and M^orgenroth to have 
l>een, llie intracelfular ferments i]ig^nt the remain- 
ing cell coimli L II eats, including tl)e thermolabila 
hemob'sic, and the thormoetnbilc hemolysin is lfl>- 
enttcd or formed in the proceiss. 

Believing thah cytase, under norinal conditions^ 
exiatA cnly withir the leucoc>U6» and tlial lU pre*- 
onco outside thcac cella ia Artitieiul, Mctchnikoff 
citct exp&rimonU elmilnr to the following in sup- 
port of hifl Tiewfi. 

Oireu R j^'uinea-pig which has been immuniTfid 
n-itli the blood of a ^ooae : if frcfh goOK corpuacla 
an! injected into tlie peritoneal cavity, the cfllls are 
hemolyTted in tlio fluid without the oecurranee of 
phagocytottie. Two e:tplanat)0us of \ht eitraleu- 
cocytJe presence of eytaae and fixators, which ia in- 
dicated by this result, are possible: first, that they 
are present normftlly and continuously in the plae- 
ma of the immuni;ti:id iimmal, or, eocoiLd, that they 
become liberated at tho time the ('orpiiwlos are in* 
Jected. Aeoordinf; to Mctchniko^, the latter eon Icu- 
tion prevaila mther than ths former. He rccogmi«« 
a plicnomp&on whioh bears the name of phaf^oly^iF. rhii««ir*i«> 
i. If,, pohition, ptirthl or (»mp!rtP> of phagnryt***. 
Almost any foreign substAnce or fluid which one 



tyrsvTioy asd jvi/r.v/rr. 

m*.y cbooac to put in cotitaot willi ie^eocvio* ^ 
•limtilatn or injures them that t1iev diinrlmrg^ ver^ 
tain of th^ir ccniBtitucnt^i. If the Bxatora ^t\4 
c I™*'!" '^)'tu*f ftri> among tlic cionetituenta whioli aw die- 
I'lijiaDirvit. chw^nl nh thf? ttmn tlie injection la midd, tiio 
extrudlular hrmolyai* onconnloroil in the pxpcri- 
Tsitni d«crihctt nhovf niijjht depend on the libera- 
tion of thv«c tubntnnoof; rntlicr timn an tlioir nat- 
nra! wcurronce fr the plasma- If this bo true, 
juid if nue roultl in some wny fortify the lenrotytpfi 
ii;r*'n»t pha^'ol>fiiflj the pliismrt vmiKl rpm^in free 
from liemolvtic power. MctchnikofT nccomplishcs 
audi fortifioation, i. o., prevent* phnfjolyeiB, hv a 
simplo proi?odnre, whidi d(?mmKl« nollnnj:* more 
tiiu the peritoneftl injocLion of a small tiinintitv 
of bouillon t>r wtlt Bolution fwenty-four hours in 
ad^^aneo of the experiment, rniflifily by thii* 
roeaoB the kueocylca have been lial)itiiat«U to the 
preB^voe of a foreign flniil, or Ihe new li>iii?oeytoi 
which accumulate posiiess greater roai&lauce. W!iat- 
ever the ejcplanation, tlie erythrocyteft \*hicli are 
injected at lliie critical time are said not lo un- 
dergo eitraeellvlar liemolyais, but instead are en> 
glnl>pd nnd diBfiolvnd by Ihp mnfrnpUnpr*. Tlie§e 
results and cthtra of a siimlfLr nature are tite ba^i* 
for the belief that cytoac normally is intraecllnlaT, 
and thnl it beeon^efl exlraccIluUr only when tho 
leiifw?}' tea arp siibjprfptl lo injurious iTiHuencea. 
The fnct Ihrit the wrum of defibrinatecl or coflgu- 
latcd btood containa cytaae is not in discord with 
finch an opinion, for in this instance nlao the Icti- 
cocrtce may be injured to euch a degree that cer- 
tain of thdr constituents nre disehnrged. We are 

riiiCOCYTQSie IX iM2tcynr. 


wr?II awnw that fllitirj Jorment n MhtitiM undw 
these piPTTTmsdircci- 

It \\ti& ^iiall)' i-lcfi treble, if pOB^blo* to flcicrminc 
th© relation of fijatora to the knoocytes. TKe 3it- 
uatton ift^ hovever, very oorDplex^ and, although 
Metchnikoff regartls the fii.itors as soLTdion or ex- 
cntioii prwlui^U of p]tugoc>r.ic cells, \hc qucsLion 
ii, perhaps, not definitely aettM. When phogoly- 
ms is prevented in the manner described, the in- 
jected erythrocytes mny well absorb fixators from 
the pTnanm Biid %i\\\ undergo nf> heniolj*ia imlil «l- 
globed by liic phagocytca. It i* considered tlint 
Gx&tors in eontnwt to oytaso inny esiet in the dr- 
cnlfltin^ pljumA. 

Phagocjtofdfl u a fcnttirc of IocaI rcsiatonee 
flgainat mtcrobic invasion was considered in re!a- 
tion to inflnmmittion. We eome now to tpaak of 
the relationalu'p of the leucoeytes to geiicrd 
atAttf of immunity, having reference tn the rendi- 
tion* which havf* been d^signaler! us natura] and 
dcqnirci] antibactcnal immunity, and natural aitd 
aoq^iin>d anUtdxic immunity. 

The first &iEpr«S6J0T>s of M^tehnikolT eoncoming 
till? nntimicrobie actiritj of phaj^Dcybv, the power 
of freeing the organism from "inradera of every 
sort/' were made Alto^^tlior from on a priori i:tam3- 
point tn an addreaa dfllivpred \ii IflSS. "Veht^t did 
Hdlkriifte dcj Oramniamn*." lie juitiflcd hie pe- 
tition on general gronnda, having Sn mind the 
"more giPii-m1 phmomma nf phAgor}1ofd4 and th^ 
reaorptioD of corpuacular elemcnta/' ai be haul 
observed them in varioua zodlogioal studies. 

Shortly there eam? to him the opportunity of 
atudybg an infeetiouft diaenie among the Dapimta 


■■■villi J (If 



tXFKcrmy a \d nr vrry/rr. 


(\vater-flea), a am^) transpArent cmvtacciLit. Tlie 
diflcosc was caused by a blastomycce which tonat 
a long iieftlle-sbiiped spora After being iwnl* 
Iowlh! L_v Uie ttuimul lie njionw |n?uTflratif thtf in- 
l«stina] wall iato tiie lody cavitr where thej- are 
Eurroimdcd, ODglobod and dif^eeled by tho vhit« 
blood fiorpueclee. If this occurred with enfficii^nt 
dgor aW the fpore* were dispoa^ of nnd the aiii- 
mftl recovered. SometiiQ«e. bowevcr, the sporos 
gQrmJDatcd even after they had become intrnectlu- 
lar^ and when the parasitic cell? reached matTirity 
thev nppaTently had the power of killing tho leu- 
cocyl*^ througli the agcncj of a secretion peculiar 
to thcinaclvefl. In the event that the latter proc- 
e$s was suflick^ntly tyrteasive the tissiios were soon 
overrun villi parmatai ^uil deuLli r&auUed from & 
«C|itic(niiic condition. 'Vhc obacrrutions vere mflde 
in tl:e living traDsparent animal. 

Although the eiarn]])o t^lleil seamed convincingp 
it wfifl, of cour«c, ncccwary that obRervationH 
aliould extend over many infeotioud proceae«e bo- 
foTf phn^rytosts na thecauKe nf iinttirivl immuiuty 
could lie at^cepfed aB a geoeral fact. This haa been 
dono on rather brood lines by MetohnilcolT and hia 
pupili, anii tlie resulu have ferred to convince 
thorn tliat the phagocybt* arc rMponablc for nat- 
ural immunity in all Lnfitancofl, and that tho dfr- 
gT<tt> of natural imnit^nity in a giren case depends 
on the degree of pjiagocjtosis which is manifested 
a^inat the oi^niein. Aa atated prcriously. tho 
microphage, with its microcytaso, is held retponai- 
hli? for antibacterial imciunity in tnuEt luslances. 
altliou.Ch the macropha^ ia concerned in certain 
fhronic infcrtioua. 



li an ftnimiil U Gu&^ccptible to & virulont culture 
of atithrai. but rosistjint to u weak culture, the 
phagocytic pciwcr 18 Jouad to Lc greater for tbo 
weaker crgaaisni. Th« higlily virulent culttm 
LTr-n.tr9( u (Mitiililinn of nitjpitira chemoln.iis, with 
the conj^quencc tliai leucocyt^d are not attracted 
and microbic prolif oration proceetlfi rapid]}'. 
Without going Ma deUili, ^ttulicH of the follow* 
in; and perhaps other micro-organ ism a have 
fltftnxtheja'il Mptt'hri(ki>fT jii Hm M^wr; cliiphylo 
coL-ci- ftlri*plfh'tK.'eiii»- piitumofOi'tn*. j;ono*?04.'eai, 
vibrio of Hinltra in infcttion* of the ;iuinea-pig, 
Ihi^ vihx-io of ^'ii09(- j»rptiiriuxji in ivliitiou to tho 
gnincB-piE* ivhjch U iintiirfilly immune, the ^\>\- 
riUum of rclapTJJnjT fcvor. tiibvrob baciMuB, yeaEt 
Ml> iiii'l i*Tht>i- fLiTt<:i. dTid certain animal para- 
Hil^s {Trr/jjiinusoma Itivigii), 

Mo«t importftnt are certnin cooditioiis whicli 
creabe a condition of nogative ehcmotasis. or othor- 
wiJW OTgng* the phogocrtcs no that U»c\' kIokc to 
take up t}ie «HSBntial organiaii. Vuillufd aaya 
that ali animals arc immune to pjrc cultiirca of 
th^ tetanus bacillus or ita aporca, providad tlie lat* 
ter havi? te-r wflsI)©T rntirply free of toxin. The 
abaonce of toxin pernuta of po^itir^ cliemotaxia 
and phagocytoiiiiit whorota toxin when present 
caiises nejfathe i^liemoUxia, an3 tie hacilJi pro- 
coed to further to^fio fonnation. The same 10 heli 
to ba tniG in infoctioDH by fiomo other or;;artBKiiiE'. 

It t«eiui« to L>L' ilL'QuiUly nlablitdied thut eiM\- 
taminating or^niiian« (pjojEcnic cocci, BaciUu,% 
protiigi<itvi) may ^eatly LDoreaie tlie virulence of 
t)ii^ biidlhis of HVT opt OHIO I if mithniv, Jiacilluji 
IVtlchiK and the tclauut baci^lua — anaerobic or- 

KcIhHiii* of 
|u Vlrnlfiiei? 

Trntlhs ■■ 




iXFK€Tio\ Axn liiitvffrrr. 

tiilifellT la 


guniicrm^ On tlic one hnnd, the Becondarjr bu^ 
t<^rtA mjiy produce more foiroroblo conditions for 
iJi* growUi of th4> Jtnii^ri>!w« Ijy consuming loGftl 
ojvxt'ii, ur, ua ML'lirhuikiilT Ui?li<?Tea, thty may «0 
Cb^fA^ t})C pFiA^ocjles that t!ie latl«r have no dia- 
pofition to tfttco itp th?T CMcntkl or^Antzm. Thia 
c^tituMlmij msy he nn important one in «ib(?r mix^ 
iiif«cUo»d, aa wljeti tJie stxeptococcus complicates 
(liphthena auJ acarlct f«ver. 

If ihe phs^ocjtic pover ia an index of the de- 
gri:« of nntuml nntibndonal immunity^ is Uic mmc 
curn!*pnuU'ncir to b(* r<H^^T»ised wlicii Uie iminnn- 
ity i^ ocquitcd ? To anawcr this quoslion satinfac- 
torily it ifl nocc£«irtry to bring pbugooytOfiia in rola-- 
tion to two different lypt* of untibactenal iinmim- 
ity whicli it ia [xjmiUe In riicoguisy. Cholera ii* an 
example of tJiat type of antibactenal Iminunily in 
wbich the buctcncidnl powur of the nerum tinUcf- 
gow n grvnl incrfjuw. Tt w slntpd thst AnHimx 
reprCMnttt aiiotbor type in vliieli tlie immuivity )fl 
not dependent on tbp bnderiHflnl power of th* 
aerum. Probably Lht a^nir may Ijr said ot acquired 
immuni^ to tlio EtroptococcuiB, staphylococcnA and 
the pneumoeocfna, jtt 11 U }>*Hiajw not lU^finitdy 
ettahUffhrtl that tlic in^niunity In tlicM* iii«Lancf« 
ia nrtlibncterial rathE-r tbau antitoxic. J''or the 
)>n?^Til »tf :iitty, ho*-<?VL'r, vith M^tchnikofT, oon- 
sidfr that the immunity w antitwderial and thnl 
it ia a eelhdar or phaflooytie immunity. 

HiiblnU w)ue]i havn Hpen immunit«d agAinst 
anthrax rcepond to sal>cutaricoLiB or tiitntpfnliin<«] 
!nj>f rinn of a tirulfixt cruUure by concentrating ao 
Ta*t a onmb^r of micropha^M at the Bite of inocu- 
lation that tht> fluid b<Tcmca purulent iu appear- 


HBLATIOS U*" ShiHUM TO fliA{iVCrTft)S(», ai7 

UUCP. Ei&ruiiiation ithaw« &d mormonA ^«givo of 
phajTOcytMii. HVhcn, on the other hand, non-JTit- 
mune mbbits firo ttiibmiU^ to eimilar inoouU- 
tions. Ih«* iTnif] wJiii^h nrciinnilntp^ lofjilly is cif a 
clear «rou» chflroctcr, contflin* few !ciicocjt«, and 
no plmj-ocytoai^ itt obitorvuhic ; tlic emimub d;c of a 
rapidly H^volopirg 3i>pticemia, From the reanltw 
miff m»\ veil mispwt that the iminiirity is n-Ialed 
to And perhaps cooxtcnsirc with the acquired pha- 
fCocjtic pcwcr. 

But i* the tierum of no influence? If hu* often 
heeu helil UhiI phfl^tHrjtii* hiki? up hnt'ti-riji unXy 
after the latter have been uijuTeil or killed by the 
ncnin or ploama* MctchriUff nnsttcrw thia objeo- 
(ii>n oi: peri men tally by in<^euUliu;* hq Immune rah* 
bit witJi salhraA. with drawing «otilc of the cxU" 
itate at a Umt vlidn phagocytoalb ia compEctc, and 
injpctin^ it into a noD-iramUDG rabbit, Th^ sec- 
ond uiimjil di&. Since nonu but plm^ocytixcd 
bacilli were injected into tlio non-tmmitcic rabl>it 
(!}, and nnce tho latter tticcumbfl to flnthmx, it 
—oin* not only uimctesBary^ but unjiislifinblif. lo 
oaoumc tlial the boctona mudt be cttcriiatcd by 
t.hc jwrtjtn bftfon> Ih&v can \w Ittlcen up by llio lou- 
cocjtes. May d>e serum, neverth<?Ie<ft, bsvi* some 
obKurt action whicb tnny not be jndiidwl untter 
ftuch lerms as boctei'icidal and altenuatinff? It 
ffljoms fflirly vffM vAtMinhcd thflt nnti-nnlbrax 
oerum. at leant frorn certain aniinnl*, mny excri h 
protective int!iicnc« when injcctod into other ani- 
inalB in conjunction uith or in advance of tho oul- 
tnro; yet MctelmikotT dE^cre^lil* tla* impuHmice of 
well protection nnd fsxy* that '*thoso pi^pertirt of 
the body fluids, m the bflCteneidoL prercvttivD ond 

TpLr tp 


tyrscTios a\d immumtt. 


■gglntinating, U\\ tiw^y into thj> backgronod in 
vn^ examples of immonit.v/^ It ia the teadency 
of tbc 5(^hool of MelchnikolT to rcfor the protective 
power of a aerum to its faculty of fltimulAting thd 
phagocytes ratlier ihfln lo it« tftcct on the micro- 
orpanianifl. Wc eliall e«, howo^r. in tpcakin^ of 
npanniTiH (p. 324) that evGn Id teUlion to anlhr&x 
the «ermft ma/ po^e^ a iliriittcl property whidi 
ficilitAtce pha^oc^vtoai?, not by atimulatlng the 
phflgocjtce but l>y eomo action on tho baot^ris, 

ront^rrnirtg tho^r disi*BMs in vhich immunity 
is chnriirl,c'ria?(l by i\ great inrrt^wi^ of the bao* 
tcTtcicTnt umboccplorfl or Tucator*. Mctchcikoff docn 
not diart'ffflTi! tbt ciietCTiee or importnnoe of tbo 
iminane Lodios^ but rather iweka to abow that ihey 
Arc a pioduct of phagocytic activity. The oon- 
<iitioun arc held to b« eimilar to those already 
majtmDHl in connection wiUj intra vxttim hemoly- 
»ia. That \s to w.y, microcytaac cxiatft only in the 
lottoocytco of the immutie ammal unricr norronl 
eondJtloiu; it eaeapa into the plasma, or tnto ihe 
apnint durin^^ coagulation only .15 d mnsf^ncnco 
of the phaffolyms already mentioned, 'l^he pho* 
nomenon of Pf«if!«r oocnra only bwaiis^ the id- 
jpclii? cuUnn- injuria thr leui?ocyt«, rPSitUinf; In 
tho hbcration of microcytaac, which in conjanction 
with tho fiialora caufieH Ihc solution of the vibrio. 
When phngoh'fiis is prevented by a preceding in* 
jodion of bouillon, phAjcocytonis and tDtrar^llalar 
ttolutioti of tijo orgnniiimF (rrtirely anpplant oxtn- 
cdlulnr solution. 
t»4»<oii<-Hii>i' 1' An immure animal rcceiToa an intrnrA^inilar 
i^maooHii>ik injecitOD of the vibrio of choicra nnd w sacrificed 
rhasflUaUH shortly, the relation of the organisms to tha leo- 

Ofi/O/y Of CITS&E. 


«oeyteft may be atudirf m stained microAcopic *co- 
tions of the or^jina (limgs). Loucocyt«» vh^nih 
have uniiergone pTiagoljsts an^ seen to be riunipril 
in the |>ul]Qonai7 tcskIs nnd in their immcdinte 
vicinity ono linda m4ny micro-orgiiiiiams wEiich 
hiivt bocn chon^d into Ui* character] Bti<^ ltsquIps 
by Uie Action of tbc c^tusu wbidi }tus esc!ap(-il from 
adJBCont kuovcrytrs, Coindilcnt with the pbe> 
nomenoR of phflgol^-eia, the lcucocyt<« lo«j t^cir 
phsfoeytJC power; heooc, no tiaotorm are found 
within the leucoc}rtes. On tbe other hand, all 
ihosp vibrios wliicb are remote from the leoco- 
cytea have a perfectly noniial appear&ncc. Phago- 
lvftt« in the blood etrenm may he prcvcnt^d^ jutt ab 
in the pcritonoiU i^avity, by a precoding injection 
L>r bimilloii iutii tlifr vl'uiiIh, I ei thin iiii(lnh»< uhvD 
Ihe <^ullur« i* injected no extracellular *olution or 
tram^fonnntion of the organisma into granules 
luki-s pfjue. but fit In the pi!ntor)t<u1 cavity. (\mt 
iJtTilruclion If (irt'otiipliKhp<! i^ntircly withm the 
raicpophages, Mf^rhnilcoff holds to the correet- 
nCM of tlicwT obiRrvatioiiK nnd infeqirelntions, n]< 
Uioni^h eontmdictoTy rceults were obtained by 
Pfeiffer and hi* pupiU^ Aa further evidence thnt 
cvluse doeM noi eiint uonnally in Uie pUsmji Metcli- 
rikolT cit(« tlie condition which u found in the 
nntcrior ehnmbCT of the <*rc in iTnm\ino anininJa. 
The vibrioa continue nnafTectBl In tbe aqtieous 
humor until vuch & time oa !enco(r)-tca wander in. 
when they are deatroyod by phaf*ocytaais. Hence. 
r)tAiu* dnra not exiit in the iKtit^^fnis humor, nnd 
if not in the aqucoua humor it ia aonely abeent 
from the plajtaa; for if present in the pluma il 
would refte!i tho anterior ehnmber by n proeeu of 




VI«M<Ar> mill 
u| rbiiicdrxli- 

fliiMri, )n Another jziKtancc n portion of a vdn. 
t'lUvd wHJi Uood, WEU red«(^fcd and contrifugatod 
withmat t^fl formation of a clot (ahfience cf plm. 
goIjeiH) ^ iLe plasma conUioed no cjinec. AIm 
tienjfou ^ollcctctJ mwJ ccntrifugated blood in tul>c0 
wliich were codIihI with pural3m^ and tlius avoided 
tlottiog; here also c^biBe was abaent from the 

U uould sc«nL, tbcQ, that two importtmt ontt^ 
bacterial factors cbftrAct«rize immuaity to cholera 
iiufi pjmilar iiif*>ctiorjs: the dyv**lo[jmeut of BpwiCt* 
iixtttora^ mid a greatly increaeiiHl phagocytic power 
on the part of the Iciicocytco. Mctchnikofl lean* 
to \}ic view tlial baoLuria, having absorbed fi»tor&. 
are moi'c readilj pbo^oc^Lizcd. but no clear idea i> 
given ad to the chan^ which the Hxatorci produce. 
However, ho ^ould rol refer tlio increase phs^ 
tjlitf powM-T entirR]j to the iiifliipnt^ of th(^ fixA' 
tore. Uc leljovea that the leucocytea of the im- 
mune animal hove psr se a hi^'ber phagocytic 
povcr tlian that of the rormal animaL In anthrax, 
for exaoiple, tlic phagocytic ponder is height- 
ened in «pl|£ cf tlie Taot that th^re b no Snen^w 
in specific i1xator«, 'V]m view, however, is up- 
povod hy DenjB and Leolcf, who found tiwt llic 
hMicoe>li'4 of the immufiv mrimal, when trsiu- 
fcrrcd to normal ecnim. had no greater pliago- 
cjiic povoT than normal leueociiicf. 

MMfhnifc'ifl hrlii>vc« that rtTators. like cytOM, 
An> pn>*1ucfsl by th« microphaj^c- That the Ijmph* 
Old orjrani may form certain 6xatora weou pii>b' 
Me fioui th«* obfierrfttionfi of Pfeiffer nnd Marx 
in nfurd to cfiolen and Wajfrrmann and 'T^kaU 

LBvcocYTW ritoDVcnoy of dytnoxiy. sai 

in typhoid, thirlng the pTO0«a8 of immnniEatroii 
and lit It i'niiv mKcu «t.mhooc\AoT% were abeent Trom 
ihe serum thoy coiiU bo domonatrulcd in the blood- 
formic^: orgnnjs (»:plecn, Ivmpli gUndj?, bone-mar- 
row), Mtl^rhiiiKiflT ftuggesfs that the-y niiiy bt? pri)* 
duccd in these orgaoa by tlic micropliagc^a which 
have wandered iu a^t«r hnvirtg englobed tii« micro- 
orRjinisniSH Tti ciictrast to cylase tlie llxalora read- 
ily objiniion ilic Icucocytoa wliich produced tbein 
and bccomo a constituent of tlic p]a»TT]&. 

The l*iiooeyto» hnvc alio hooa hrou^ht in rcli- 
tionship to JUititoAii^ imintiiiily tind tht- forriDUiuii 
of aiitito£uia. Id cxperimeuta] tetauua exudaUi 
which arc rich in leiicocytoa contain more toxin 
than dow a AimilAr quantity of blood. That is to 
eajf, Ihe Ii-uctwyloi Iijivp tl*n jiowei" of sihnftrh'mg 
toxina, and it is htlU thut (he natural immunity 
of the animal dopcndR on Iho doirreo to which thi? 
power is pri*MeiiL Thi? imrnmiity at the ehickrji 
to tctuua depends iiot on ELon-flUKeptiLite nerve 
oella nor oa the prttonec of natural ontitoxiii, but 
on th« flhscrliin^ pow^r of the ]ouoocyte« for th« 
toiin^ Not only do Inicorytci aWrb tojiinjt, hui 
it is held Uiflt tlicy aIbo are the producers fit anti- 
tozintf. Aa comparn] with tho «ido-cliain theory, 
It ia a pw-'uliaiity uf the view uf MdeHaikoIT tliat 
•BtJIoxin doce not Tf^rrr^cnt a eonatitucnt of Uie 
tknu celts, but rathor the toxin itself, which has 
been altervil by l^ncoci'tiG activity in a manner ai 
yet ob«ciir«w 

In pnssiTe actitoiio immnnity the idea fit a 
Hii'mStnl union W^uvrn toTjn azul anLiUixin i\t)vt 
not Qifct with fcncml acceptance among the np* 
holders of the phagoc}ljo theory. It It aom^tiiiet 





i^KMCTtUff AJ^D ildUVMTr. 

•ud thflt ontiloxinn are cfTiranioiH from the fact 
that th^> stimulate phagocytoeia (al>«orptic>i) of 
Uw* toxin, th(r luttrr then mffrring i!tt!Qtq^lioii 
iu tlie leiicocjt**, 
innnarr, Thc foliowio^ fltAtct&oit^ fiimnuimc the phvo- 
cyttc theory of fmmtinit^v i* conceived by Uctcb- 

1. Hntural immunity to bacteria dcpeudj oa 
and id coejitcnptve ^itlt pha^^rcytofia und nitbie- 
que&t digestion of tha roicrob^t, Intr&lnicocytJc 
dftstniciLiin of the micro^rgnniKiiiM i* nimmjiliilinl 
hy thc (^t^ie, posnhly at^ed hy intraleticocTtic fu- 
ator>. Normal serum 10 dcroid of both fiiatovs 
and c}-tace. 

2. Atirjuinsd iitirmtrlty U: Imrtt^riA r1i-piTriiU <m 
the ^abliahmcnt of a heightcued phagocytic power 
as the rMalt of l[nzQuni7Atir>n or inflection, la 
dwun Ilk? nntlimx, ed H-hidi fUatorv an- not Jn- 
crc^aM^f thm nr^ power in an act^uired prap<'rty 
of the leucocytes an*! is independent of any in- 
flu«nco on the part of the eenim. In diseosee like 
cholera, tlie new fijtator* wtiidi are fortned inay 
render thc micro^rganijinns more auaccpUble to 
phagocytostB, but thia ia prot>ab1y aecordnrv to 
Lncrwwiyl fiiudinEi nn tht^ part of the phafrocylOtf- 
Both cyta*c an*.! fiicator are produced by thc pha- 
giocytic c«]It. U\ ftcqvircd active immunity to 
bactcrJn the ftxjilor* nay Iw fr^r in the* wn^m 
and plu^ma, but the cylnae in iitlnKf?UulAr In all 
ca«rx cytasB becoraea ^.ttrjkn'lliiUr only as thc re- 
sult of phigolyBia. 

3. In piuain inmiunity to bacteria, aa when on 
aittlbacterial aenini la injected for tho take of 
prophylvcif or ertrv, thc #crum a dBcncioaa chiefly 



because it fitiraulatca the leucocytes to mcTeased 

4. Natural immunity to toxins depends on the 
power of the leucocytes, and perhaps the genera- 
tive organs, to absorb the toxin. 

5. Active immunity to toxins is established 
through the activity of the leucocytes, by which 
the toxin is probably so changed as to constitute 

6. In passive antitoxic immunity the antitoxin 
presumably acts by simulating the phagocytes to 
an increoflctl absorption of the toxin. 



AlUjDugh Uie importance of the indiionc^ of 
tlie tcriiiM in p1iag<»cirti(! ]^iccii<»ni hilv rcrnfiii/^rl 
br Dtnvft flQil Lck^Jcf, it romniDcd for Wright nnd 
lloiiylwn Ui dpmntislnlo thnt frnbstancot eml m 
tilt serum which are ai])al>1tf of Trmlpring hnrtiina 
nfftcfjilible t'l pVioijoovtfrti^ The name opeonm 
whl-\, ilii-y ^pjilii'd l^^ {h\s nxih^iance hn» came 
into Ectifffil MfQ. 

TIk' proof of tiio action of opeonin on haotona 
■wftn hwKOfJ on the foUnftfng fnrfjt: 1, When tliB 
ffffllj <li^fJjnnalL'(l Mood of some oniniol i* niued 
with Iho tiiltviie of n ■uitublo niif'ri>"'>r;ianUm 
(*tiij>)iylfwofviJB, fit'*pto<^o(M*iifl^ nntlirjii bnrilliis, 
*tcl ami placciJ in llie [li-irmoatat for ^0 or 30 
nupijtci^, ttfiirrd prfpiirnlionfi of tlifl mtxtjrp nhow 
llmt tlie pciKTnorptioniiri»»ar Wiu^tiL-jtes tyintflhi a 
Jaigc Jiufuhcr of tlir microlwa. S. If, howcvpr. oil 
the «vnim ii washed front the hloo'1 ht^fon? Adding 
Iht^ m ir ni- c] rpi II]"' II w, [jriit'ti«^alK no hafUria are 
in^lcd. Thi^ shr»wf Ihc imporianc^ of the s&rani, 
but i]oM not diirerenliplo between norae effect On 
\]n' \v\icaf.y\,tt-f OIL i\\K one hnncl. ir the hurtrris, 
on ihfl oUier. 3, In oi'der to decide tbid point one 
inav enbjpct the fii^pention of Ijfld^ria to tb* 
nflion rf fnr%\j ri?iT-fti'p fccnim, ntiH nUi-r a mnrni't 
of nbout 30 tnmut«» ren^ove t\\ tb« fcnim b.v cea- 
tnfuj7AtLr>n. and miit thp "flCTnj;itis«?d" cntlur« with 
KiTiLirufiiv h]o(]d; pha^o^vioKi* orcm"* nlTrort to 



the *Hinc i!(»ent» na wli*n tlit" fr«*l] ikfi^rhinlwl 
blood, cimlfijiiiii;: ffrrum^ is iiwil- ThrTU- iv»tiUii 
ffscm to jthovr ilc^nildy thut phQgoc-,vtc»U licpcnda 
on the power uf thi; optoniuA to alToct tbc Imetcria 
in iome pccuJlur manner. 

T^tj^r t«i(peririieiil« ^liowt^rl tlmt llir 
power of the biyod vanctJ in the (^ourae of ilistese 
jtiet [Li IS fouDiJ in the laeL* of other immune mh- 
sUnwe- The relation of euth an abnormal opinio 
pnwcr to that of tinrmnl Kpmm vns (ipsigniitPil njt 
the op^nir indfi, 

Tlic Wrighl trcJinio dtala with three factOTt at 
V}\\ bo appjin'tit from the bL»ovc: Itfueocytea, b***- 
Una and scrum. 

Lericoc^tra. — The Itucocvlcd arc obtninrf iu dif 
fcr^ntvayeai'rordiiij^to thckinilemplcvcd. Human 
l9nCQcyU» an.' ohtuiued L^v puncturing the loh« of 
the riir «ir tip of the finv-ei' with a small lancet 
and iJLtiliing the hlocKJ in u 1 lo 1.^^ per cent 
solution of ^oiliam (itrute m V,S^ per cent, aodtum 
t'lilcni) wilnliuit. The mitukTiit uf blood neoewar^ 
ia ubuallr bmalh About 1 c.q. ind IC c.^*, of citrate 
(<))tition 15 roquired to keep the Lilootl from dot- 
ting. Bj ovntnfugali^ing, the tnrjniaclps ar* 
Mparated froiu the citrate solution and tho cor* 
pAiKiCF wn^hcd by pipc!ttirL)f of the ttupcnmtant 
fluid aud replafinj- it willi phyaiolojjic aait boIq- 
tiOD. Two fiurli wflfiliicgs are made and than Iba 
pcarh-colorcd blocd rrcaru containinc the Icuoo- 
exlos u rvinov«d from the turfuev of the rod ccUa 
for ^w. 

5«rtifm.'-'rhia i« obtainad m for ai^lytinatum 
or other ta»t«v 


t\r^£VTJOX AMD iMMvyinr. 

fheteri^ — ^71i» bari^rb am dbuined bj groving 
OB Ibe fUrfiice ot an sgir sltai for from 12 to M 
bmm; tbey ar« tJi^n mDOred into salt Mtetioo 
ttithvr bir Bwrna of a loop or by oiHing IIm mII 
voltilion rlirvctly to the agar tlftnt. The eon€ <» 
tratinn »hon7d be fqcIi tint a smear on a alUc 
•Jiov pltntf of bictcria to tbo fitid of the mkto- 
lacopc; whiJc at the* «ain« time the iDdivBdnal orgwn- 
ifliM ar* wll BPpftratpd from ont anoth«r« Fr^ 
<pieiUlj to (iblim lurh a niiiUr« it <■ uvosmt; 
to tliake the oiiubaoii Ihonxislilj to uitaro diTi- 
fltoo of diunpe. 

Hariai; tbo aW'e coivtitutnti th«F art mind 
together in tbo folloiriiig wav : 

A capiHarT tnhe \9 m^A^ br drawing oat a gla« 
tube of about 4 tnm. t^liber anil a tvDgtb of about 
16 cm. A nnail rolmie of senun u allond to 
ma into iha tuba bv capillarr attnctiou and tbt 
leogtb of the TolDne ieark«j od tbo outcfde of 
tbr tabr- A Hma!! air bnUili* whaot 1 mm. n 
lengtb IB tkcD dtavik into tbe lube asd tkea a Tot- 
mutt of bact«ria] euapviinoik «^ul to lli« tolum* 
of ««ntm^ Again a nutU babble of atr » diavD 
inlo the lube aDi] Ustlv a roluron of leunvjta naix- 
tma equal to thoee of >enim and bacteria. 

I'bo tbiM cooftittjcotB arc tbco nixod legcttf t 
bjr drmwmj^ tbo dim up into tbo largo put of 
Uv tab* aD<I miiiag to^rthcr tbtre br drawing 
back and fnrlli or they majr be mixad oa a glaai 
§l)dc aftd tbfn ilrawn bark ialo the ca|>Ular7 tale^ 
Th« mutnra U Ibaa iBcabatad tbt dadrvd IveHi 
ol time (uraallj about 1ft mioataa) and tta mnd 
on a blide av in making an ordinary Uood smear. 



The slide ia then Btained wJlU no appropriate 
ctnin (Tor mcwt hnctei'in i^no of th? ^OBinAtet of 
mtth^lcrifi blue) iiD(3 cifimincd with 11l« uumet- 
ttion lens of a mitrruAtfopo. 

The number of bocteria in iiTOGe«ftive Uucocytei 
Tfi counted and flu ftTcrnge made. VnrionB ftgurw 
ttfe givQii A£ iho nccessarir cumber of leucocytes 
wliirh sliouUl !»ir onitntwl to gJVi? ac^iirnt^ ri^fiulte. 
The nunil>err however, slicuTd be govi-inr^t] bv the 
QiKifon&ity of the nunibcia of biictonn in 6ucce«- 
■ivp kiicnryt^*. If, for iiiHtanre, ilin atpraige 
nuntbrr of bflrt'*rin in i\\Tvy. Ktin:eKslvr oouiitK f>f 
ten leucocyihi m nc^drtr the anme, it i^ more ac- 
curate to take puc}] an averaga than if more lonoo- 
ertw" lire comijUiI "ith ro niiifonnity of miml>pr«L 

The r«tio of the arcra^ aumbcr of bectcrift to 
the leucocyte tahen up in the pittfence of u %xT^Jk 
ftenun to the flverago number taken up io ch« 
pmtetice of a «erirm Ukea as normal is the opsonic 

By the immuaixatiort of aziiin«l4 by various 
bacterj« anil otb«r cells a aernm of bigb opaoDJc 
povcr mat be prodiicn], Tlii? ci|woni<i tctJon of 
eudb seruna* in comtraet to that of n^^nnal ^ciumr 
ia not dwtroyfd by hontin^ to ''<i" C- and diffore 
from normnl npuitiiti in nUn*r rvupppt* which wiU 
be dijfuned later. In iinmii&iimf; amoinln with 
typhoid badtli^ it waa noticed tliat the catimation 
irf thi^ concentration of optonin ir the typhoid im- 
utuiK? H^nim by tlie Wright metliod of cumparlton 
did uol ahoiv noulta tb^t vould be expected, Tbat 
iSr a -highly immune animal would «how little 
diffi^rciw frcm one with low immunity. Klien, 
therefore, estimated tlie optonic poitcr by dctctm- 



IxmCTltiX AAU IliliVXlTY. 

mug tlin (lilitfiGr t>oiiiI at nliid: tlii* number of 
bfloteiia tfttoD up by the Icucocjtei) oqnflls the 
nnmWr itkcit up bvitticnit tlie prvii«iio« of wrum. 
This dilution jioxqi ie Kim^icc« calJcd the point 
of <tpBoiiio extinc-tton, Tho phagoPv^loeU lakinj; 
plnn^ W]f>]orit ihn inHurncv of (vrum u known hh 

Th(TT« h«j b^cn foneiderablo conflict of opinion 
a« 10 vhethvT there ar« flpvcific optonini in normal 
dfrum ffli- cliiTcrrrnt vnHpticJ of cclU or one opsonic 
eiib^Unce capatilo of acting oji n variety of celUi 
HnklDc'ri roncKicji-tt tam hi* own Btiidiw? nntl thow 
of otheiv, consisting of eptcil^c nbnorption cxpori- 
monts and oba^rvaliona on the ftpecific fall in 
opeonio power following inj^cti<?n of specific anti- 
gf'ii, and hnin ntlirr ni jXTiiiH^itM, Uiaf, normul 
aerum coDtaloa appcifxe opaooiiis wlijth arc cnpalile 
of ipacific flb«orption and wliich aro tho eflin« 
siihT^larn't^* whif^b are iiifrt^aeod In form tba im- 

The immune opaonine are easily demonttralod 
by absorption *iporim<^n1fl to be highly ^ppcific, 

H«lctOtfn aJifi Rnoiligrr havc< (hown that nnrmal 
opfoniiiF ftre Hlmn>t rtjinp!inrlj tlt^troyotl or inacti- 
YBtcd by hai and nx*- Uiel'ef^>rf^ thennolabUc, The 
inactive npsonin (f>peoiioi(5] by unturating Ihfl 
re(*|itorji nf bnclc-nu M'ilh lhrt,linij|i>plinrt' ifnmp 
prevenla furtli*! aensitiiation with fre*li serum, 

Thcflc inv(»ti^atora aleo show thai opsonin mav 
b© bound or nfrutrali^Ptl (imikrljk' to oompltmcnt 
hj H>hilintis of vnri<iir* niIU, 

The natui« of inunune opsonina haa boon the 
eubJQCt of utuch diflou'fion. A? wa^ &taUd before^ 
Immune cpvonina teshi a l^njpcrature of fnini <*J£I 

SJ.TVJtlC OF opffoym. 

to 60* C. IVniti, C'owif nrd Cljjipin, and others 
hfltc ahown, hovevor. that Ibe opaonic power of 
heated icrum miiy br^ iiicronncrl h^ tho ndfjition of 
Dormiil w*njm Mniilnr to tlifit ronrtimtioii taking 
place <n addint: compi^nicnl l<* amborcptor* 
Browcin^ hafl pointBd <iut Ibal this apparent BJm- 
ilarity of the adinn nf rormgl i^eniio on heated 
op^tmiii mftv he due tti Mimmsition of elTpoU. He 
hA5 «houQ that by eepartiiing immune body iii 
opsonic w^nlm at 0* C, by Minrfttion witb bftctcriu 
and (bi>n nddinp ^i>mplfmf»nt thorp ip a truo acHv- 
(ilion, mid Ih/tt nn *iiHi artmr* oc-crirrrd in tnmHn^ 
the ba<d(<na nith roTiiplunienl, ^ritnlim^ nml 11ic?n 
oddiDf heated opsonic Mrrum. lie c^nclndcfl that 
Immune body and cotrpkment moy be coucomod 
in opsonic fiction, but leave* open tbe qutiticm of 
whether (ho immtin*^ body i» (be Uiermoi^Ubllf 
opeonin or noL 

Hcktocn couoJuJes from llie f'>Hoi*ins la'^U thai 
opgoiiint 6Tti distinct from other antibodio^i. 

I. Ucat mjiy iilmoul cjmplet^ly destroy the 
opsonic power of nertiiu leaving; the lytic ombo- 
e^ptont inUH. 

^. Scrum, normtil mt wtU ajt iinmune, may coc- 
t&iii opttomii for 3 ;:iTen oi-j^uUm bnt not. at Uaet 
00 far fie ia kno^m. the proper lytic aroboecptor lor 
thflt org4ini»ia. 

3- A eernm may c^Mitain opsonin for an orgsn- 
i*mj hut uo M£*^hrtjnm and the opviionin may perifUt 
after deftlrurlioa of baeleriolytic compleiiient by 

4. Id immunisation lytic and opaooic powers clo 
not run para:i«L 



isr&jTJos A.V/* iSiuv^rr^. 

•c»i»aiaK ttt If Hi niittiiml if* iuJK'lnl wiLh a projret duw of 
l^mii. bacteria or alien red celle, there resiilte u 4 rule 
in the Uni <Tay or «o a fall in the opaonie cotit«nt 
of iht* liiruv] a\ottg wltli oUjpr jiiitiUnlics, Tlii* 
period ia known oa the "negati^o phapc.'' and i» 
followed by a siwidy rUe which rotichcfi its height 
from the ffi^htJi fo Uic twelfth dity iipd gradually' 
fa11» ti} Konniil The orgatUei jdiaae as pointed 
out by Hekt^es ia epccijic end it hai not been 
det«rtnin^ whctlicr it U due to s specific abeorp- 
lion 01' lo Ml ^CTeit oa the autibodj producing; 


''Ia aevcral acute iufoctioufi dieeafi«e the course 
of tiic fornation at tiQw opEonm for the jTifvcting 
agent, ill Uie typiffil nltaci, terfuiuatiuy promptly 
m recovery without com pli cat ion a, shows a marked 
guncral resemblaticc to tlic opsoniu and antibody 
curve flft^r a alngle antigen injection in the 
normal animal; it ol»o bears definite and constont 
relatione to t!io clinical phenomono, Durinj; the 
riiHy >'tag(*H wlipn thp jiymptoms arc pmnonnred 
thiTie i* n negative phase ond (hen us the a^-mplomi 
bef^in to »ub*:dii tlie opsoniu curvL' rises nlov< 
normal, teaching the highest point i^everal dHja 
aftrr ihf imw^t, followed hy n ^tudMni siibsidiMKy?. 
TJiia is true of the pneuiuococciia opsonin iw piwii- 
mcnia, of the opponin for the cliphtherirt barillas 
in diphtheria, of liit- *trep(o('(jL'cii? opsonin in 
erysipdas, and aleo of the cpeonin for tli« dip- 
tococcue of mnmps in thai diw^se. The t-nvv^ is 
typical also for tlis sireptocoooii? in *rarlet fewr, 
iudicaliii^' oleai'ly that this organism unqueation- 
ably plo)^ a definite role in Ecorlrt fever, whatever 
it0 Bctnal cnuiativo relation to the dioeue nay b^^ 



Tu piivomouia llie gr^tt^l Hm in the leucocj'toMi 
•ppon to precede somewhAt (he highest riae of 
th« optoniiiH In nil lhf«9 dUcRses the typical 
w&tV'liLe opMinin curvv '\s moiliflei] !>v llif devel- 
opment of conpiicdtinnn of vnrious kinda fln<I at 
the onset of vhkh it eommcnly iitii^l^rgoeg h diic- 
ttnet deprvraion, hi nipiii)1> fatdl coees, for in- 
ataneft of pnonmonia, the opinio turvc or index 
may not return from Ul@ primary deprt'S^ion. but 
ftiiik Ifmcr and lowrr. In prolonjicd infeetioDii, 
gTjneral as veil && looalj tberd oecur irrogular 
riiutiiatium arjil hi dirfmk, more or It*ft* stationary 
ea«ei, the epionie index is oftm ffubnormal. At 
thii time funhor detaiU CEumot be givc&. My 
chief point fi to m^ke clear the elcse s^socintion 
betweeD recovery end the wa^e-likc rive of t)ie 
opaonin, end^ os ii result of the immunuiitmn io 
all likelihood dIbo of other oitlibodie^, in tha 
typical atUck of acute eocnlled »elf-Uniited IQ- 
fectionB. In s^ome of Uie diseaK* (he opsonin ia 
the only antibody iliat w< can meaeure readily 
with our [irrt4pn1 mpnnf. Af I haxn Ktatedj an 
intraphBgocylic; dR»truelJ0n of pUETiJinot^occi nnd 
tttieptococct tdkea plaeo m thu preecnee of freeh 
laucoeytM and opaooii; fienini, whoreaa either along 
rouHiitiitiv u good mifdiitm for IJKWf hrtrterin. 
Taking ihi!dc facta into account it acema fo me 
that tho wafe-liko coureo of the opeonin in pneu- 
monia and in ac^t« atraptococciig inf^tions \% a 
atroitg poiDt tni ih<* iddn of thir MigUHl imptfrUiU-'e 
of i^ia^ocytoAia in their healins;, irhaterer other 
m«a«are, of whi*h at present we know leaa op 
nothing, n;ay he in operaltnn nlaa"' 

L IMNMf Opuonlfife anEl Oi%w AAribodloi, Hcl^nM, IftOP. 



«f AcilAK ar 

An pointed out br Qtnin indl Cox, ili« vorit of 
Wri^l and lila ff>lIowen Iiaa resulted In an uodup 
iK-jEloct of tbc importftncc or tlic TATMtion in the 
pov^r of tcUGocjtoiis in the l^ticoc^tot themselves 
H» ^ fni-trir Iti pliftgocrytois, Tlipy I'Rigiliaiibie thm 
fact that while tbe <l<teniim«tiiMa of opDooic iwwr 
mtj bo tn indtnUoD of lh« d«gre« i^ fmmaiH'r 
it doe« not tpprcs^t th? pb«j:oc7tir povpr nf thr 
blood ftA « Thole. In order to 44cerUiii the 
nitiotion of tho difF«rctit compoiwcits f«p«rtt*ly 
&uU aa A wliole Ui«*_v suggest Ui« comptrnoo of the 
lencocTtf* of the blood in <pi«stMm with tboce of 
normal blood and oall the ratio of tlie fir«i to the 
se^'ond the c^'lophiigi*' inileii. Secondlr, Ih^v eont- 
p&rc the action nf the Icacocjtcs mod the fcnun 
of the blood tn question with the action of normal 
leiieocylefl and («r«m. The ratio of the first to 
the Mxx>Di! U culled the cipeonoejtoplMgie indtx. 

What hn« comfr to be known at the hvpothe^id 
^r Wdch U of ttuch praetical and thforttical im- 
poitanre that reference to it cdiould not b« psMed 
over, h mar be put in the form of the followinjc 
queetion: If bacterial loxina and the eonBtiltKota 
of bacterial cells so >ct on tb^ inaoe oelle tliat the 
lallrr pmdiiciT hodiM (anliht^lW) vhirh nre in- 
imicnl to tli^ bacterM, whj mmr not the bodr flQid« 
in turn m nrt on the bactorU that the Utter pro- 
dt»iv bodies (anlibodlK) which are inunk^l to the 
tiome cell5? "l>wfccd at from the point of mw 
of the bad^nttm. a« wll $f from that of the 
aninul ho^t. arcnrdln^ to the hypotheiSi adratK«d, 
the airaiutlc between iht> b*d(n-ia and tlie body 
celb in infoctiont m^y be eoiiccived a$ an ink* 
ntnnmn^ contHt in which e«ch partkipajit ic 



ttiiDXiIatei] hj iu oppoQcMit to the jiroUuiaiou ot 
cytotoxinfe bobtlle lo the otlier, nml thertliv en- 
dottTtra iv in»kc iUclf immune uKtuutt it» ou- 

A xnoTi'. renHnriii1i]« hypcitWU coiilrl Iianlly ha 
adTfluc<^. and no amal] number of facl^ known 
n1 th^ (iTi-ccnt time nrc in hnrmouv with it. 
Walker had jili^eudy perforiiittij vork of a fmulji- 
tncnUl chai'artcr, which ithcwcd thnt the typhoid 
bftciUufi, n-hcn grown id the presence ot ils and- 
rt-i'tuM. HLijuin^ ^H'hUt vinili'iuf fur jiriimjils, 
t'nrthcrmorc, n greater ilosc of protective tcfvim 
W46 required to save j-uiuea-|>ip£k& from inf<*tion 
Viiih the iiniikimim^f) f^iiitnre than fraui the >ianie 
ftrtin which h*d not been immimiied. The fact 
hort booti kDuwu for n long time fhnl Xhc ty\*\\aiii 
ftociilue resiftfl a^lutlnatloD when frwhlj cul- 
tinted fiom n patient having the di^eara, wherem 
it becom^Jt i?a»Jy iif^jfluttiiubh^ nftc^r a period of 
ftltificial cultivation. It mav veil be ns^umod that 
Hit* barillnfl, whrn pljivitig Ihr paH nf nn 
OT^nifiin. CTaduaUy van immunised a;;ain?<t the 
aAJltutiTiatini propertit? of the patienrs scrum; 
and> OR the other hand, thnt it lont thi= Tf^ii^tAnr^ 
uftrr it held Wen tiMTiover) fnini Ihr ^tiniu Idling 
jnflnencc of the infected tody. This immuni^- 
tioii vith affphTlininp niflv be i^anied on in the 
t<-itt g\n%f. and hm-ti-nn whif-h have hei^n vo ttvatod 
acquire tli<^ power to ab!<urb h xtvntcr rjimntitr of 
iigflutioin from the homologouB aerum (Hail). 

Anotlier pertinent oleervntioa waa that by 
lVeeh*ibpr^, nho funrd thnt A aCrflin of thp diph- 
tiirriu iNirillo^ whon tfrown in n mi^Hujii rrmbiiji* 
infE diphtheria antitoxin ccidd tie made to pro- 



due* dipMlicrifl toxin more abundaallv. Wc may 
Di^Bimio tiipt (he luititoxin combinoH vitJi thd cor- 
re«|>nndiii^' r»ri.^p1on4 AitirnteLl in the WilSi {i}|ph- 
tbem toxin). §n^ that the bcrUU were, a» a tesult, 
stimulated td produce a greater Dumber of Bueh 
receplunt (lotiri}. 

CnnMitE^nt nn thcKi- o!itir;rratjoii« an* rriHx iht 
hjpothoaifi «ndcr diwxis^iou, Welch mcntil a gtc^t 
deal moro tJinn the imiDunbaliaii of ihe bar^leria 
again&t tlte def«Dsnc powers of thr nninial body. 
Not (*nlv nuiy a Imctmum di.iMnc iiifi*oiion become 
more reaiatjint to th<> hndpricidjil ni^tion tif the 
hodj hjr producinK antibodiM for those bactericidal 
QgT^nci^, (ir by it^ ability to abnorb and dispose of 
a ercnter <jxiaiititj of bactenotv^in ; and not only 
iiiuy a bjiLteriun^ be able lu re^pontl to the prc«eiica 
of iititurnl nnlitoxinjt m the body hy the prodoc* 
tion of more toxin; but. in ftddilion, certain con* 
Htituentfi of oui h'ltly flitid^ Timy, by combining 
with suitable bncturial receptors, ttimulatc the 
bacterium to Hit production of a whole eJiower of 
cyiotoxin#, wliich nltnclc the lpiil<ocTtps, erythro- 
rj'tr*, mine n:!l», Hvi^r, kidtipv, r-ti'. The nature 
of the aniiital siibstaDoea which may combine with 
the baeUribl rccDpton; aitd ihus oaii^ the fonua- 
tioiL of the Ira* lerioi^L-nu* rvEolnsin^ ik Ipff htj ojipn 
question, and ia not of ea^ential imporlintcc for 
the theory; it i« not at all nccewary that they be 
(oxic for tJie bat'leHttni, and they may wpn be 
taken np aa food snbstancea. Like>t-tN<^ Hie pomihlo 
natLin* of the cytotoxiufi proiluccfl hy the bacterium 
ifl of secnndsry importunes. It fto happcnad that 
^TeM1 aRtujncil thai thi-y rai^ht be of the nature 
of ainbo(«ptor», which may become complemented 

nYpoTUMaiR of wbich. 


by bactorifti compTomcnt, bv the ciivuldtiii^ com- 
pltmrnt of Ihu b^jd^ or by vn'lot-orriplenienU of 
thS ti»ue ceHh. Onc^ cojM »ith equal reoflOtabl^ 
ness fieeumo that tiic>- iriay be complete toxine, 
TOCtptorR of tli« wconi^ orcI«r, with a lisptnphorons 
and a l<)jiopIiciroiiJ» wtrut-ltirp. 

A wi*ll-kr]o«n *jHtvriu-iit of MdcliiiikofT is to 
the effect that k partkular bactcnuin when vim^ 
lent ie not ko readily taken up by Icnoocytcs a> ia 
an avindput strain Thin fjift. Iiba hp*>n j\fiM re- 
pcfttW!)>' in reci'iit times Jii iUv ftxjctj of phngocy- 
toai* m the tc*t lube. This may be becaviae the 
orgsnieio, in itn vimfcnt parasitic state, Bocretee 
aubstuccif vhU'h roppl the pliagocyto*, Daatralu!e 
djp ujjsoniri^ ^r bpCHMio nf the formation of aotual 
leucocytic ioxini. 

One of tJic moit widely known plionomcna In 
rohtion to tbc virulcnco of tome or^ameins n that 
their puthogonicity mar bo incr^fled by paaelng 
tbrm lliniiigh i^tiituMr' utiin^iilH ri'prjitfd]}'. Tha 
btrt iwulU.Jirc obt^iinm] when intcirocdiatc arti- 
iicial CTiltiTation ia avoided and tl^e inoculatiouj 
arc inad« directly from the dtMi) into tha living 
auEuial. It nmy, with all rtaiou, bv tittumed that 
by contiuued rt^iJi-mr in l\\v hai ihr. hmTlt-riuui 
haa been trained to produtx^ a jfrentcr ijaantity of 
U>xic eubatan^jfl which an? luimual to the hoat. 
and that tha ineroaacd virulence cf th^s pnraaitc 
dtfpvuds uri ihja couditiou. 

Although up to Ih^ pmar.nt lima aratematie 
atteinpta to place ibe hypothe^^is of Welch on a 
Arm experimental ba»i» appear not 1o liat'C been 
made, the ohwrvulioiw cited, aa well ai othar« 



cvidcnco of ita ooiroctEiOK. 

alrtivt ia liic? rto-caJleJ afe'^jtMiu Llwory of Bail, the 
CMcatiol pomto of which tnnj be j^mc without 
«titenng into & doiailod (li«c-tiBsion. 

Bflil s1tribut«<6 lo pathogenii- b«<^tei'ia the prop- 
ciiy of "nggrcfi^ivene**," througli which thty 
dirciotly unt^t^oui^te the proU^tiv^ agenoje^ of the 
bodv. The ruii?ro-orgaTiL$Tiia of highest parasitic 
juiwpi'ft, tlie ''true pjirasJl^ft/' fis thosp hcl^n^ing to 
th<i brTnarrhngic ^ptJocmi/i group, poF&cw the 
^}Zt'eutL<^t ui;px<^i^*«noaft emco they are able to pro- 
lif*»rntr' in ihe blood fltr^fim whUr the nniiharlpml 
iictivitir* ^^^ the boiK (phnjtdoyto^ij, rU:.) nrr held 
in ahevonn^. Otiier bacteria, which ia caosing 
(TiVnee tend To r^maio lor^aliireclj s\tn3, if by any 
irii*tu(» they rrflj-h thr JfhMxi sfu'aini, nr<» rot hbk 
lo proHfcnte Kreatly in this place, are lialf 
paTfl«it«e" aiicl Jiavt a lon-erdcjereo of xggremTt' 
n*"**); 1h*y «ro more »utt>pp(ibte to phA^ocytouf 
ami to 1lic nrtloH of iMcti^nohT-inii (lypboid, 
cholera, d)i»t-utcry>. SiipropUytes have uo aggm- 
>t7« action. 

ThU U i-erv ^rvnt, htii Bail ani^ liU rcvvorfarni 
liavr itlUjnpir<1 to put Hit concc^\iiai ^Q an c:tpon> 
mfnUl baaU by demontft rating the escktCDce of a 
fitibetanco on whicli th« apgrcwjTtpai a of hactoria 
iSi^priKlt; to thU Mibbtaiioe t]i«y giv«f the iiuiDU of 

Intnp«iitoiieal inocvlatioa of the nibcreb bteU- 
lut into tbo gnin«a'pjg Iradi to nor* or kM 



gCDf^rn] tubtrculoetn anJ to tbe ^e-«th of tJi<? auimal 
in the cour» of n fow wcokt:. If, during tho 
fourw of Ihe diwaw. a tiecoml injection of a large 
quantity M the hfldllun i« ni4i<Ic info thn }tcritoncfll 
cavity, or if nn injeclior of tntwrcjitin is given, 
Um* aiiiiiml lii**! vfi_v i|uitkh. Tfii* i*, of rourw^ 
tiothio^ more than th« woIl-knovD liyperaTucep- 
tiMlily ot ivh<iT<iu\ffUi animal* lo tho product* of 
Ihc hilM*rrli* IirHIIus, In udilitinr In IIiij* fnrf, 
howcvfr, a similar rcaiilt was obtaini^ in Ariuther 
manner. Tf a liir^ quantitT of bacilli U placed 
in llje pc>riton@al cjivitj of u health^' giiin(*n-pi^» 
and the exudate is removed after t^etity'four Tiaurti 
und freed from Jeucocytee and bacilli, tha a£:greB«in 
of the bacHlvi la iaid to be present in the oL«ftr 
fluid, This la demonatrated by iajacliDj^ aome of 
l!>c iiuid, tofccthor with tubercle bactlli, tnto the 
peHioncal cavitv of anoihor healthy jjiiLneft'plg 
The rapid death <>f tho nniiriMl i* the result, 
whcri?fl» tlift bacilli rtlone i'tiMn: denlb only after « 
loLf" period, end Ihe eelt-frcc *XBdate ulonc ia 
witbo^Jt toKlHtj. 

A aimilar rondilion hfla bicn foond in expert* 
nKstfil iofectionji with a number of bacteria 
(typhoid, cholera, dysentory, plojnie, chicken clio- 
lera), the ewpnti»l fftet being thp ^amer that, fol- 
Icming iatraprritoQcal or intraplciirnl [noculntion, 
the twultini" t?*udfttc, when freed from kukocytca 
ftnd bacteria, ban the power of inteniifyinff an iD- 
fiirtioii hy t)if forrrvpcrLiliii;; organitni. 

Tbcr« >ecm2 at present to be oo definite knowl* 
cdico eonccniiuf; tlic nature of tiic«e aKfrrceamaf al- 
though Bail thiulcs they may r«aomble true t^iina 
in wmc rc^pM^I". Likrriw thv prpciw character 




of thtrir nrlion U unknown, allhough Bull aud bU 
co-workcra ore atroDgly incliiied to the view that 
they iniii^it piia^ocitcsis by iomu direct action of 
the le«oocyt«B, 

It is furthtr interofllicg that immuui^atioa witH 
BggreHsiufi is entd (i> pive rite to tlie formntion of 
aiiUaggr&'^in^, sikI that by tite use of antiaggres- 
Birc eenira tJie actii>a of the flgCTeseias is neutral- 
ized, flntj the ha<?tona conBeqiJently become the 
prey of the leucocytes. Tlie ijctton of thfi unU- 
aggrc^ivn serum is taid not to depend on the prcB- 
gncG of bnt^teriolysins. 

Proof of Ihc non-iJentitj of the nggrcesina of 
Bn:] nnd the toxian jiroducod by the organiGiD 
has not been rery conviQcing. 

Jnrcstigoting the rc^iflinnci? of Tirulent pneu- 
mococci (which vary gently from noti'vinjlGiit 
forms) to phngocjtoek, Ito^now irns fible, by au- 
tolysis in Slit sohitior. to extract ths stibstunce 
on wliich tliii reeJEtanec d^ponde. H« vaa not 
only in Ihi* way ab\e lo rentier them filmgocytiihltf, 
but also by treating non-virulenl straina with this 
oxtract he vrjiR nbfe to render thom more virulent 
and resj&tant tu pliHgorvto»i»<- 

The aubtttance which he ealla virulio is ineoluble 
in alcohol and ether, and ia thcrmo«tiblt. 




Ill ISftB. beforo The discoTf rj- of toxirw and niiU- 
texiRf wJ before iKer* wna aiiy koowle^lge hb to 
the real u^ti^re of immunity. Elirllcli^ publi^licil a 
udqU Tolttmc on th« '*l)xT^n itcquiTomcrJii ^f the 
Bodj-'' HeTcm the belief was «xpr«u«d that ihft 
iSKimilntioD of foo6^ by cdU i« «ccQmp1i«bcd onljr 
^er chemicftl unioG hoa taJ:en place between the 
food subftanco lod som* constitaoDt of c«]Lu]ar 
pTolopliAiii, It li not the underBtaudtiig Umt ua- 
■uniUtioD is at ad end, however, when this union 
baa occurred, for nrrlAln moleeulM of complet 
chemical DfltcTc and of gr^i ai» muat be apUt up 
Into almpler mbataaees before (hey can enter into 
the rompcuition of pfotopI*Mn. Therefore, thocell 
cooatitvetti vhicL ccmbinoi vith the mitriUoTi* 
molocule sorvn only aa a liok to bring the food- 
tfsff Into relntinn with th« diga>tm, oxidixiog or 
fanDefitAtiTe activjliet of lie cell. 

Ehtlieh ipeaka of that portion of linng proto- -t^i-ttt^c^ 
plaim uh]>b reprctents the cdlnlar aeHntJ^a att vftu-cilVikB^j 
the "L^tnngihtni" of the cell, the center of eel* 
Inlar actirity, or the central irrotip of the pTOtc^ 
p1a«m, whorco^ tltoao chemicfll frrcupa whioh bind 
the food Mibstiino^ iiTfrnlleil thpnirl^-chainnof the 

Th« author of tlio tlieory haa made hu concop- 
l. DMv au ■ia«v«iaR«Kiarrbl» At* omoiiatiML 


x.vfjtcnuA JAU tuAivMry. 

tlon mora langiLle ihraugli &n aQatogr whidi v/aa 
drawn with the w-cnUcd ring or nucleris of bcnxol 
and it4 flid^chaina. The molecule of bctizol. C^H^, 
hrts n (Wniir formnHnr in which each rflrhon 
atom ia Unkccl to two others in auch n itiaiiiut ju 
tn fnrri n ring; three valences of e^ach carbon 
fttom arc ^utisficd in tJiie way, and the fcmith b 
flatiat^^d by utomii of hvdrogcn, ones of which in nt- 
UiiliPtl to fach carbon atom, thus: 

H-C *C-H 


lliiB rin^ ia unnloRoii* lo tht " LriHungfktm" of 
ihe cell, A ^^reat vanelj of eheniical compoumla 
eiiate find very many raay be produced «ynlhcti- 
oflUy by BubptitutinK 'or one or more atoms of 
hydrogen, one or mnrfl othergrmipBof ntoma vrhich 
may be very simple or very crjmplux. Tlie groups 
which hflve been sabstitntod nrc called sidcKrh&ine. 
Thnu bnnKOic ftcid is forme<^ from benzol by a«b- 
BlilutinR the acid rHdical COOII for a particular 
n, niui Ihc COQH in this instance is a siiie-chain 
of the ring : 





Just ha Ibe Gide'cliniiu ol the " T^Uitingxhtm" 
iTAv combine witb food pnrticloe, so may the aid©- 
oliflXn» of tin? Iwizol ring pomlnno with olhnr 
jfTonpi oF atoms luiJ thereby awinitlate the UifL-r> 
flO to ftay, into tlie rmg. To chofee ft aimplc cxam- 
pTr^ thi^ eotJiiim of flodlnm liy^roiid may unite with 
the aidfr^bnin COOII 1^ inrm sodium be!ns!oale, 
tho hvdrogGn of the acid radical being replaced b? 
Lbe^odivm, lhu«: 

" O 

V * 



Prwiimftbly it is in eomo such manner aa xodiam 
la brought into relationship ^f!\W\ tbif lH^nf>l rtii- 
deoa. in the example cit^J, lliat the foofl nub* 
jtarcea are broaglil into rektiotwhip with tho 
"Ln$iung»k<m" of the cell. 

I'be liypotheais of Ehrlich cornea with it the ««piin»iiBr* 
aj&«i]inptioii timt tho fii<!p-th.itiii; of a cell possess or 
cuutiat of ilefntilo grnujiH (}f atoms i^npnlile of miiL- 
icg chemically vith certain oUicr definite group* 
of Btorni in tlie foo<! pnrlicl^fi ; lienoe both the aii!e- 
chain and tlie food fiiihstance liave rombiriing 
gronp^—baptophorw. The sdc-chains of tho ccUa 
Ehrlich now calla rec^ptCTtir element iirhieh we 
have nlrearly rnro^iwd in connection with im- 
mintly. Inwmucb a* <liffcrpnt foof!.4 bavc differ- 
ODt ehemical corDpoaitions, it ia hkeiy that their 
Mndtnj^ ^roupoi are not identical; and if thin be 


n'FSCTJQX AMD iJlift/A/ri". 

irne there must exist many kinils of ret^epLort eitch 
of whicli U nble b> unite 4>ti1y with timt fooil «itb- 
stence vbich hna a corrcsronilin^ binding ^roupof 

In contrast to the i?oaditioii with rcq>«ct to 

fDmlHj I't it hold thitt cfieinTcnt t^iiMHiiceB of knoTD 
compmition, drugs an^ olkaloids never become in- 
corporated OS s ptrt of the protopl4isin. tfiat iai 
thcv tlo n£>t unite with cell receptors, although 
tVoy mfly effect the vitnfity and fnnrtion of protrt* 
plnsm pTofmindly. Thrir iniibiUty to yield aati- 
bodies aa d rosult of immunization m FUppoecd to 
ilffpontl on (hw pondilion. Such siibsUnces^ up* 
LtinlitJi: tu ElirlicJi, ii\j!^L jil lie cell ui a condition 
of imstoblc! »nlt forrnnlion vith w>me con*tituenl 
of th@ protopTiLSTn^ or In & atat^ of solid solution. 

The following stflternont from n rnccnt publica* 
tioii by Ehrhcli tfummnrixcs tJi? nutritional upcct 
of tic tboory: '*W© ra;iat aflanme that all Bx;b- 
ntiin»^ wlin^h t^ivr into Ibi* Hlrur^tun* at prnto- 
plonn are fijwd chcmicaUy liy tbo protoplaam. Wc 
faATO AtwByi diEtinpiifhed be1wL*cn ojifiinitUbld vaib- 
riancffl which serve for nntrflioti and wTiioli enter 
into pfrmnnent tmton vnth thn protoplfwim, and 
those which arc foreign to the body. No one W 
Item that qutnin nnd similnr KiihstniTc'i^ nn^ ra- 
frimiKted. that ia, enter into the composition of the 
prrtoplnsm. On the other hand, the food Bub- 
Rtitnoes nre hound In tho colls, and Ihia tinion muat 
be connderod m chcnucal. 6nc con not cjttiact a 
migar T«eidiiiim from oells vith water, but mnit 
fintrt nplit it riff H-ith JidiU tr nwirr to i*l ft free^ 
But now anch a chemical onion. like eveiy ^m- 
thom«, domncd* the prctcrec r>f two binding 

groups of msximAl chemical Affinity, which on 
tEuitPil one to th*? o(!i(?r. The binding' ^raup» whicb 
rceji^o in tlte cclU and wlitch Vmd fmxl snbstafiOM 
I <S»iipintc 05 ekk-chnine or r4>ei.-ptorR. while 1 
TiBTp cbIM ihtwe of the molef^ilp* of foodfitoffs tlie 
haptophoroiis irroups. I iileo lusitmc that proto- 
pbam u eudovvei! with a ]&r£:c ecrios of »uch side- 
chffllns. ivhidi through their cl]i?ink^a1 oonatitutioD 
flre aUe to bmJ the ilifferent foovlftt itfT-^ nn<l Ihsri^ 
by provjrle the premjubite for cellular melabol- 

If tho sido-cham theory of nutrition is to bo- l'*'-*^'*"*" 
corao tbo sid^ehflin theory of immiinitv it is nee- jui*^ »• 
nvmry thnt if- nriJfTrgr> 4'Tnhfirntion in orW thul tlic 
forrnniioa of niitibodicfi mar be adequnlcT;^ tx- 
pfoJDOd. Tf, as EhrlJch aa^i^nioe, llio union of 
toxin with er\\ r«'t'ptor» ciiuhbi thi^ owrprwiHcUon 
of the Utter as antitoiln, adcI >f (hb tmion ia ac- 
nlogouf to that of fooil itub«tancc« nith nintilnr rt- 
rppiofii, nnp mnv wnmlpr thnf; nnfihriHipe nm rnl 
formal for onr ortlinnTj foods, untihodi** which 
vonltj be dischnTg«d fronn the ^lU an.l which 
would unite with Hrculntinjff nnlritioitc pnrtidcft 
flnd thereby bring: about a condition of starTftlion. 
Without crlCTinjr into the intricn<^i<^ of this i^ue*- 
llon. il cfvma probable that normaUy a condition 
of physiologic cqnil i brill Di oiists b<?tweeD the food 
aubtftnnccfl on the on« hand onfl tJic cellular octivi- 
tl«fl on tho other, p> that Ihe union of food with 
pTotop]s8m constitutes no ahooriniil idimitluii to 
the "Lfistungskem" of the cell When, howevftr, 
cells an diverled from iheir normal metabolic 
functioD b}' unioD with toxinv and otiier "nbtkormAl 
food nluElnnco," the effect 031 t)w ctll ia de- 



scribed aa a ^\ defL^ct^ Llif ct^fnct consisting of tbe 
functioniO clioiinfttion of the receptor. The "/.«(*• 
tiin^fikfrn" as Uie lital or rc^itntinj; c^tcr of the 
lell ri'[ifiirw thr iJrrfH bv tli« formation of new rc- 
ccptora, anil in harm^ifiy with tfic hypothesis of 
Wei^rl prmluc«« not only cnoufrh to rcpnir the 
defect, but a ^reat t-xccfis, wilh 1li« rp»nk ihal 
many are throwTi in(o tlie drcnlntion, 'rh« anal- 
ogy of the "Lciaiuit^kcm" mt\x the bensol ring 
ean not be (^a^H«tl lo llii* uitttbU for thw latt^T hiu: 
no powM- of rq>iot?i.icing fidc^hains to take the 
place of one whieh liaa iocn bound by some new 
Xroijp nf afrjma, 

ft will b« iipprnprifltp in this plaw to consider 
the cliaracter of the pi-oof irliich has been offered 
In Hupport of thp thfoe tcncta which eonatitute the 
frnmr«'oric nf Ihw th™ry t^f Khrlirh, ThPW three 
teneta may be expresbeil as folfowa: I. Antitox* 
ine coQTitoract toxine by entering into chonucftl 
nniori with Ihem ; a fiimilflr iininn !akp« place be- 
tween other anttbodjVa nnii their bomolofcus niV 
etances. y, Tojcins in injoriEg oelh combine 
chemically with a delioite wnuititnpnl of th(» proto- 
pla*in^ tlic cell receptor; other aniigenoua auV 
etimcee^ enter into minilnr union with the flppro- 
prifltoTeeoptoTB of cells- 3- The spocilie aatibodiof 
of ihp stfnim are new-formeil receptors Identical ID 
fltnicturc with tl^oge which, on cell contftitucnt«, 
had combined with the homologous antigens. 
First tenet : Tn the enrly rlnyH of j^tudia on tm. 
Aorii><><iii-H mniiit>' (1890-1897), the action of n toxin and the 
a"fi-T c(!ipncy of an antitoxm could be determined only 

li ftblt 10 cBiur lti« rirrmtlloa of bd uiLlbodj. 

Cy/QIl OF ASTJa&DllS wnil AMiaBHS. 34B 

bj tRJoctioff thf«c stib«tancc« into llTing Bsimali. 
and UiQ anima] vxporimcrt tkaturaDy continuoe to 

be tho rtiMns of teeting the curative and prophy- 
Iflf^tic vnlucB (if mruTTits. Sri long, hf>weTpr^ as Biich 
experiments were perr^rnied cxclmiTel^ in tbc IIt- 
Ing uniniBl tJie nature of the aoHon of antitoxin 
reinairjej to n pertain extent in *louht It re- 
mained iincarLaln whether antitoxin in protective 
becatitfe it actually destroys the toxin, t>ec-ai3fic neii- 
tnliKfltion of a chemical nature occure, or bccoMec 
in Bomo manner it incrr^adcs tho rG«istanoG of the 
inocuktt»d animal. In Chapter XTI expermn^nts 
vivtv citpil to fhiyvk- that aiititrjxin t3ots nai ilchtroy 
the toxin, find thi^ in g>:ficnil]v admitted to-doy. 
There continue* to bo lomc difference of opin* 
ion, however, in relation to the two other poft*ibili> 
tioc, U o., oa to whctlior antitoxin combiaos chomi- 
Oilly with toxin, or h Mcucima bec^aiiw of iU 
•timuIatiDg power on tbo tieanca of the animal. 
B»hrin^ thp diecoverer of antitoxin, wai from the 
bcgimtiD^ an cxpooeii^t ^f the chtmicol theory, cvea 
nt a time when th9 eoneeptions of Ehrlieh hsid not 
b<CD fulJy developed. On tJie other hand* eertain 
noted invo^tigatora, capecially Itoux and Bnchner« 
nnd later Metehnikof?^ etcod for tiio alternative 

Followirif- rlrHf'ly on Behnn^'a grvat ditcorcrr. mpin bb* 
Ehrlich etndied tli« hemug:i^lutinatinK toxin rictn, 
from the ea«tor-oil beivR, and hv immunization 
with it produced a tpeeSfie untitoxin. t c„ anti- 
ricin, Ricin in toiit fti rrytliroijlM hoLh in the 
ftDimAl body And in the teat-tube, and if it coold 
fce dbown that antirkin prote«1« in th« teet-tnbe 
by a direct effeel on the toitin, U »M ht^ly pfoln 


ittyMVixoA AifD iMUb^nr, 

(■P4* flf |h4t 

ab1« flmt lU action tn the aninial bod;f wotUd be of 
a simil&r natam> The rcnxlti loft no dcmlt in the 
mind of Ehrlich that octincUi unite* chemicallv 
with min, anil the Applirability of this pniiriplr 
in nrimal cxpcnncnta bfsrnme aU the more ftp- 
parent vheo it was thown tbat the proportion of 
ftnttridn vhldi pTi>l4>cbc an riirty jiUa prote^^ tn 
]fivo. It U M<\ that nmiljir proof of chemical unJoa 
batwie«n bactohal bemolxaiiu, the hemoTjan of 
rpiimn ati"! tTut Ipurorirfin f)f the stnphylocacaua 
with their rrniprctiTo atititoxina is eqtiallj valid- 
Altlionfrh the attimfti body can not be dispensed 
raqTr^a'i^iion with in tdstfng the aolion of the antitoxina of 
^'^itfiulAiT- diphthpriaund (ptjinns, t^rtnin principle of rbm* 
ical action arc fonnd to prevail vhich leare do 
doobt in rqn^ to the chctnicaJ ncQtnUiiatioik of 
di« tozini- Tf neulmlUinf? proportiow of dipli* 
tkeria to>in and antitoiln be mixed in a Int-tKbe 
and injected immediately, the aernni doea oot b^ 
ford abealnto protection ; i^ bowcrer, the mixture 
if AUov«d to atand for fron ^fteen to twestv intD- 
Qtaa before Injection, tlte protetiodi ia abaolobi. 
Thia alooe voald poont to an ftctkm of th« eoli* 
lozin on tho toxin, for tbe ccmplctioin of vhich a 
ttmax aaooAt of tinw la reqoired. ¥ta tbe eoa- 
plde BontnUntioa of telnnsa teoin b^ ita nti- 
toxis about for^ Muantce art nr<N»ar7 at ordinarj 
t^pflntnraa. Tlmn eertain alhtr cbernMl princi* 
plM dneribcd in Chapter XII, are found to b^ 
tne: net &entn1:nth» proceedt man npid^ 
el bigW tt«i at Wci tcnpentnee, more rapiffir 
fa cakcentraM tiuu in dihtte aolationa, ai^ tint 
tt talsM place in enordnnv* viih the lav of anl- 
t^da proportMUL 

UNION or ANUBODiae \ytTU AyUGENS, 347 

Granting, tlicn, tliat neutrali^ntion of toxin by 
AJititoxiu U of ft ch«iiiicAl TiLititrE^, the firet esseittial 
Bt«p in the rlicmicjil or wMe-cLain theory ie ffltab- 
tishcd. H nnlitoxin combiner cJKniicnlly with 
texiD> union rnuiit o«ur through comblDSng groupa 
which eut'li tnoleHjiil^ pos*i^*#w, nrrrdn lie* the ex* 
perimcntal justification for n^iumin;: tlic ciUteacO 
of haplophorouft fironps. 

The (dttiatlon ia more difUcnlt in regnr*! to thn 
ituion of receptore of th*J second antl third orders, 
i- c. offllutiriinft mid amboetplorft with th« ho- 
mologous recepl-^rs of hnrti-rii atiiI other cAU. 
One t-An not Utrnt^ hnctena aj^^bRt agcfUitiniii or 
boetericidal nmboccptors ao (^XAOtly a^ toxin can be 
tihntad Rgaitiiit uotUoiin, for, in Iho fip*t place, 
it ifl difficult to obtain at will a dcsircil conccntm- 
tion of bnetcnn and to keep it without alteration, 
and, in th& HW?oad plw*, bflctprial rcIU f^outftin 
many more rrct?ptor» tbiin nrr urr^wiHry f^r tJinr 
Ojotlnti nation onfl aolutioii. A ^ireii TTin^H of bac- 
terid will take up v&ryini^ qnfintiticft of flj^g:lntintn, 
depending on tlu' con (^(^nt rat ton of ttio Inth-r. unrl 
tho Munn principle applitit to Ihc; abHor(itioii of 
baotcricid&I mid liemolyiic amboceptors. As mor^ 
wid moro agjrtntinin in ncid«i3, Xhn \o\a\ amount 
■h>Hirl)i*[l incri^oxn »ith ench additiuii, nltliouj^li 
the ratio of alr^rbed to nnafasorbed o^lutimn 
grovH l«« coDtinnoualy. Hie conditions which 
govern thiiK phcnomnnor luv not undrntood. 
Perlupft tm com1[tioii KfiwikK m^^r^■ dwtHively for 
diemical nniou of Ih*^ bodies with tvM receptoM 
than immtinizfttior f^iponir^ts which were ear* 
it«d on with oell* wbic'h hml hwn trvatod with m 
gnst ftKCM of the spedfic antiflernm. The ii*- 

ql1h Oil 



Ton DuDgcm vitli the predpitiD* »eciD to «hov 
thAt etich intracclliiJ&T ^Terprodaciioa actitaUy 
doM (>ccur. TL« ttpeHmcfitt c«ac»m the f«t« of 
"Mftjaplnsrai**' (fliiMna of tbr Kjiiflcr-rmli) vhm 
injected into Uic diculatioa of the mbbil (we 
tborc). H a ninf^Ic injcctioD of tlic cemm is 
girui. a flpoc-illc precipitin for the klter boi^y in 
due lime may be deioonBlrated in the eeniiQ of tiie 
rabbit, EvcntHaliT the precipitin disappears from 
tho cifcnlation bv excretion or otbn mean. At 
Ibit tim«, when all llie prvciphm lins disnpppanHl, 
one may Bffiutne that the cells of tite nitir:inl iitjU 
oontain an iocreofeii number of precipitin recep< 
tors, although tbe latter are no longer prodaodd to 
audi ni\ extent that they are t1:rt)vn into tiw rir* 
onlAtion. If thi« condition ext4t« the tianea of 
the aniinaJ at this time Kho<a]d be nble to abaarb a 
larger aDKiuDt of the forei^ serum, giren in a aee- 
ood injection, and perhaps obtorb it awrt rapidlj 
tban tJie tiaanofl of an untreated r^biL Uaki|: a 
Kpc^ifir pnvipitaling tErtiin in ordi-r fn clHrc-t 
trac«e of tho lordjEn eemm wbicb cUU remained in 
the blood of the injected animal, ron 1>ung«ni de- 
termined tbat ita tiasoes actnaJly do absorb the 
plasnu more rapidly then do the tueoce of the 
antr^te^ rabbit The oella of the former ha« ■ 
greats abeorfaiag power, i. e.. a greater hlndinf 
power for the ptama; therefore, an incrcaaed 
numher of n^ecpton, 

Tlwae eiampla arc, perhaps^ wiBJdeait to itloa- 
trate the prtnciploa of eapenmentation whidi hav« 
baa followad in tha attempt to obtain dednita 
proof of tha corm t t n e aa of tJie «^!j*sti&1 ponnta of 
the tbeory. The mnlU arv in entire aenrd with 



the primary na^ximptions antl ebow that th© theory 
coTitinu^ tri sfrrvo na nn cxpIiLnnton' b^uis for 
ticivly-diiicnvrrcci fnclK, aut\ tw n f^LJiiflntinn on 
which new rcvcarchf« may be inntitutctL 

In atldition to tho three niatD prindpleo treats 
of fthoTo, \h<^ following poiplfl are n&ceeearily m- 
€hi<3i?cl ill A fLurriiTiary of the viowK uf Khrlich, rnaDy 
fnctA of n ooproboralit^e iifltiirc having Iwcn nacor- 
(niiiud ir»|jend4?ut laborntorita*. 

1, The rtcoffTiition of (iiflercnt t>pc3 of Uaeiie 
rocq>tor^ E>y which poculiantice in th? action of t1t« 
different antiboOi^ are rxpEain^il. llcccplnrG of 
the Urat ortler, as antitoxins, anticomplenicnU imil 
antiamboceplore, are i^^ar^icd en relatiTtjly sitnple 
bodice bccuuNc no other confttitucut con be rocog- 
liiKed t^^n the hartnphoronK group by wbirh thrj 
combing with their homologous »uh?it.anftH- Re- 
CCptcn of the MCond order aro n]cire> complLcat«d 
In that they havo aometlting morr- than tht? mcTt 
liiitdinff power; utually they are able to produce 
eonic obicrvobic change in the atib^noc witli 
v^iich they unite. Hence, each bm a toiophorouR 
or a zymotoxic group in addition to thr ha;ito* 
phoToni, end the two irroups arc port of the same 
inolc&nlo. Toiine, agglntinine, prficipitine nr\A 
complpTTWof* nre rrr^itorn of th« iira-ond onlr-r 
Ilecept<>rs of the Ihird order, i. c„ the hactctjo- 
I^lie, hcmolyfie an<l cytotoKi<> ftmbocftptor*, aro 
atill iiijre cumpk-x in thai i\wy are^ 60 to t<ay, only 
partial antibotHca, the complete body coouHting of 
the amboccptor^omplcment complex. The ambo- 
e^tor iu not an active body, but f«rws ftp an in- 
l^niietltLiry body to tfinnwt the active Knhfttance, 
complement- with the cell. In Ihe cytolytic proo- 

Ollivr tmiifiV^ 
(AUf I'rln- 



•« the uii!>occpfi>r through iU c^iophilou* biptt^ 
phore fint unitw mth ihc celJ, and oa a icBolt 
ftcqnirea an Increated ftCEtnitj for oomplflnMiit, 
Willi which it titiitn tbroii^h its rompl^menHv 
phihuB hoptophor^. Only ofUr Ihis 6otibIe umon 
i« completed may complement atfoct the oell. 
Frcm tills it follow* chat eomplciceut ic the cyto 
Ivtlr pi'ocan doaa not combiD^ with tlie cell ^i- 
rccUj. Afl prrrJoii«Iy stated^ BorJot and otbcn 
oppoae the idea that the atworptiou of these bodioa 
U of a c^hrmicnl nAtnrOr rofif^tilt^'ng it nttlitfT tn tw 
a phydcol proce«H. 

lilKrlich hiu intimutc^cl hi« belief that tietfUG arn- 
bocq^tora plfiy th* chief rfilo in tho fi^cntioik of 
ftiorli; liy thr» wll* of Ido bculy. 

2- T}ie dieJ^li^:al theory ciploifls tlic spociticity 
which oharfictLTizcK th« formation and action of 
antihniliE^. Every anijgen ]\a» a haptopliore vhicb 
U different from thow of other aiitijr'''iia ; eonao- 
qnontly. H imitos only orith the oorrespondisg coll 
rcn.'Hplof^ nml f.hi^ IntU'r wiif-n nvrqinMhu^«Ml mid 
taat into the circulation rPUins ita specific binding 
p(jtrer for the corrc«pondinjr ajitigcn, 

^. Tlie rriultfttitle nf mitibodi^ which liuve Wn 
ohtaine^t indicate thnt tlic ccUa contain a rfl«t 
nnmbpr of difTcront ripceptora which corrtepond to 
tJie Ihrec lJp*-'^ now njciDgniHil ; Ihaf is, there i« a 
diffprfTit antitoxin Tocoplor for every kind of 
t'ltin, vie, 

4, Flirlich Viaa limited tlie application of the 
t^m tonn to these aubatancci of animal or plant 
ori^i immuniaalion with whioh eaiuies tho forma* 
tian of spei^flc anlitoxln^. Other oliamcleriHtic? 
hAT« been given in Chapter XJ. 



5, Itcceptore of tlie second order, toxins, sgglti- 
Hntnp, pa«i|>itiH3 and ccmplementa, undergo m 
pecnliur degeut^rabive clumge, Bpontaneouftly or aa 
II result of exjiodiirt to iojurioue agccto, in which 
the toiophoroiis or Eymototic group disapp^ra or 
IB rendeitxi inai'tlvc. Tlie temunation -oiil i» af- 
fixed to the altered bodies, as toxoid* a^hitiiioid> 
procipttoid and complomortoid. Wcchaborg bw 
dMCribcd a aimiUr do^imerAtion of one of Iho hap* 
tnpl("ri3 iif amburaptora, falling thp proclii^^t: iirn- 
boceptold. Toxoids and complcmcntoida on im- 
munixatioit cilugo the farmntion of corrcnpotiding 
antitoxjna and fliitlcomiJ^einentK, Uy viftn^ of rtv 
tention of thdr haptophoron^iL grou^m, 

G. By m^ne of a special technics datitod for 
Ktt^dying tUr* rkriitrjitixnlimi of loxin by aTilitnxi:!. 
i. e,, the parttflt aaturatioa method, Ehrlich found 
diphtheria toxin to be a very oompltrx fiubstaiiee. 
Kot all tlk^ Mio!e<'nl«fi of the have tlie name 
aRiAtty for antitom, ocd according to the de- 
grees of their affinity have r«c«)ved tho name« of 
prototoiEn^ deut^rotoxin and tritotoxin. Simi^ 
larly, protoxoida and iiyntnxoid* arc rnolecutcu of 
toxoid having difforcnt afllnitiee for antitoxin. 
Th«flG conditions aro repr«»oiit»d grnpbiciiHy by 
rneanB of tht- "loxin aprclrum" i](«:rilH?(l pre- 

7, Ehrlieh claims tJiat the dipbthena bacillus 
wrrvtca ttto toxina^ one of which eauwn ^e Jic^t^ 
maaifeatatioiia of diplilheritic intoxication, wber^ 
a9 tfao flocond lo\in. i. e.. toxoo, haa a prolong 
tnruhdHon piTifM mid prohjiMr rjiuvfi dipbthenlic 
paiuljui^ ToioD tias a ['twrr eDtnity for dlpli- 
thtria antitoxin than 1h^ other oontlilnenU of the 


kjsrKfjTiojr Jkyn lu^ivxitr. 


toxiQ colution, but ift DcutratiEtfJ by tZio ««mc Rati* 
toxin, TJjiK Tiew ;« Mtrongly oppoi^d by Arriie- 
Diua and ^UiUen, who. working od tbc ba»a that 
ihc ncittrnltuti&n of toxin takes place Hccording 
lo ocriain lawa of phv^iciv] c-heiRifitr>% cliiin that 
tuxon in uoLhing more thaa toxin whick liaa dioo- 
cialed from the toxin-ftEtitoxm rooleciile. 

8, It iB thought that tho inculvition period 
which chtracterixes the action of toxins ivpi^sents 
lo a largo de^gree Uie Unie re<^iiired for tbc action 
of the toxophorctiA jToup jift«r the toxin haa boen 
bound by tho c&lh. 

9, Klirlich ttflni^H for llic mulliplicily of com* 
p1«ni«nU in oppotntion to Bordet imd othera who 
claim tho ^lidcoice of but odo coroplomont 
(rtjpxin), TliH vHriou* comptementa ilHTi^r m tJie 
nntun: of their haptophorcs, irifiiout regard to 
poMihk' ilifTeTCncoE in their xymotoxic groupf^ 

10, Duly tho»e organ:* which liave AiiitaMe rc- 
ceptor* nmy produce an nntibody for a given anti- 
geo, \. «., only thoBO cells wliich luay enter into 
chmrtic^al irnirlnnation with tlic juitigt^n. It does 
not fotlov, howt>«r, that only Lhofe organe which 
Khow clmicAl or onatctnic leaiona may produce* 
nay. an antitoiin; toe oth^r organa not so suacep- 
tiblc to the action of the toxin may £til] posses 
the auitabia rcceplora And coet tliem oot ts anti- 

TJir? vnriouN h'|ies of ImTnunil.y arc cxjilainnblc 
on the boais of tho Eiidi?'ChaLn theory in t1i4 follow- 
in;F ti-'rms: 

1. Natural immunity lo toxins may depend on 
(a) a lacic of jruttablc wll rf^^^ptor*, the toxin coa- 
Boqnently flndiii^ no point of attack; {h) a v^ 

yAfUHS ot' tuMuym\ 


Jovr Dflinity b^wwn ccU roceptor* and tosdo *o 
iliHt the laller (ToeA not unite with ttie ce\h except 
under Bpccial cooditione (c. g-, the immuBity of 
chicken to tetauus) ; or (c) on tlio presence of 
natural untitounti. 

?. Acc|iiir«d aottve antitoiio Imtnunit; dop«ndf 
on the multipltcatioD ami I'Jtcretian of cell recep- 
tors (nDtitoxin) into the circnlntion, the new- 
formod bodies having the pr>wcr of combimog 
<■^«nic-F]llT with adilitionftl train whifrh may ha in- 

3, Tn^irc nntito:tic ifumnnity, a« catablishcd by 
the injection of an antitoxjn^ dcpcnrfs on the ahiU 
ity of the antitran to combine diemiailly with tJie 
tciin and Uiua to ilivert the latter from th(* cells, 

4. Natnral immnnitr to bnctrna dcpcnrls on (a) 
a lack of nitfable cell rweptora with wbidj the 
toxic bacterial constituents mi^ht combine; (&) n 
THJ low alTnit^ between cell receptor?^ and the 
IoxIq bacterial con«titucTita; or (l) on the pretence 
of natural hoc tcrio Wains (amboeeptora and eom- 

5, Acfjnirtil actire attttbaeteHal imnuinty de- 
pends on tlie [nuUiplication and excrction into the 
eirtulation of specific edl reccptora (amboecptore} 
which ha^e the power of nnitmg with rompleTnent 
to kill tbo micro-orsaninTL^ which mar be intro* 


6. Pnsvire antibact^ml immunity, us eatab- 
fiiilieil liy Om injei^liuu of n bactenoh ti<? «-nim, 
depends on the ability of the ainboccptora con- 
tained in titc aerum to unile ehL>mically with the 
r«c«ptOTa of the inicn^-or^nnii^m. aa a result of 
which complement la abeorbed to kill and pcrhapa 



tsrtfcrms axd tuhivstTr 


ft nil 

Jo >liB6olve the bflclcrJa. 1T>c complement i^hj ba 
prMent in tlie wrum which is injected, or the nat* 
iiral coirplem^t of the In^ividofll may be utilise 
by tJuT a[nlK}Ci!}>torB. 

WJien one fieeka to comparv Ihe tlieory of Elirltcb 
with thftt of Mctchnikolf, one finds Ihtic more in 
tommon thnn the pencrnl purpose of explaining 
the [>In?[3omena of immunity- Yet it is remark* 
able llmL where thore is so Hitle iu potnmon Umre 
arc 60 few contrudictionn of an essential ruiiure. 

The theory ol Kfirlieh bos thot dc^oc of JeJl- 
oltenew which it must have in order to l>e a plau^* 
bie chemical tlieory^ whereas that of Metchnlkolf 
seems more general in that it ifl bo largely biologic 
ami vitaliFitic. 

Each has a nLTtain relation to nutrition. Pha^ 
cyteitia aa a ttii frit ion u1 nien^urc is fauiiil in lu^ve^ 
lypL-s of tinimnKaml Jiccoinpnahes notliiug fiirllier 
ttinn 1q briii^ the food Enl)ftflncu in contact nith 
Ihe digLsLivc fprmtnt* containeil in tfie cHI. Tn 
relation to nutntion the theory of Ehrlich bcjeiii£» 
£0 to aay» where the phaifocylic theory leaves off. 
involvings a.^ it ilop*, the nittlKul hy which food 
flubstoDccs become a part of Ihe protopl^m, 

Mctchnilioff, with Khriicb, reco^Jzee the vari- 
ous untibodiee whieh hnvi* hnm rlJKmvi'rfHK Tijc- 
former hold* that all are prodtinctl by the phogo- 
cylea without pugge*ting clcotly a method by 
which they may be fnrmnd. Ehrlich a^aiUTiea a 
very precise method by which they may be fermft^j 
hut ileHi^^-natM no partic^ilnr ci'll« nj; their [iro- 
duceni, dialing only in a general wa^ that an onti- 
boO.r ia produccti only by those cclla witii whidi the 

Ttniurtias vr Mt:ivuxiKOtJ\ 


■niigeii may oomliine; [n ftome In«tATic«tt, tVie leu- 
■Doytcs moy bo such cells. 

The theory ot UdelinikofF is not eoiioenic<! Tv^lh 
the stnidiire of tovins anH tVip vsrioiis sntiktdlee, 
nor with Ihe ircthod by which toxins mfly injnre 
the cell*, whcrefls Ehrlicli preaents flefinite conccp- 
ticna OTi these points. 

Botli recognize that there is more than one cimi- 
pkintLt (tvtast^, Klirlich reooguizea iin liiniL to 
the varieljcft vliicli may exieti ^hcrcaa Mctchnihtilf 
dotcrihcf but ivo cyta^C(> micnx^ytase And mncrro- 

The view which Metchnikoff has expressed. th«t 
antitoxin is prodnccri by eomc rtPtion of the pha^o- 
cvtes on the toxin, i* directly opposed to that of 
EhrlJch whicli recognizes antitoxin as a proili^ict of 
the cell iUclf 

They ngm^ that amlweeptors (fliatora) beootn* 
i<xtrnc.*cTlular in thebTood, 

Metclinikoff holds Ibiit complrmerla (cvbues) 
nrc producod only by the phococytfe and thai 
thete subBtancte stq found' in th^ plninna or wrum 
only o« n rwiiH of injury to the piha£0cyt«e (pha^ 
lyma). Tht^ pointa are not invoWcU cMcutioity 
in th^ thfon- of EHrlicb. Certain IntMtigatori 
who work tik luniLouy uJtJi tJie ndc-chain theory, 
4« well 08 thoae who rcprctcrt the vicwa of Metdi- 
nikoff, h%v& extrdfited complement from the l«nici>- 
cjtfift. Some of FlirlichV «nppQTlpr» Ivliuvu tlut 
complement exijta normallv in the plasma. 

MotehnikoCT and EhrJich hold direr^^t ri«in 
conetrming the iK-tion of untitnxiiist, thf^ forroer b^ 
liering that antitoxins fi1imu1ai« tlic pbagocytea to 
an incroued alworption nnd consequent dtttrtiiy 


iyf£CTtoy Ayo /iTi/rxjrr. 

tion of the toxin, whereas Ehrlioh duras that 
antit^Eia neutralises toxin bv combEniog chemi* 
cfllljr vilh it. 

According to KeUhBlkolT, all type* of [mmuDitj 
depend, dircctlv or indircdly, on pha^orv-tic activ- 
ity. While tho iddc-chniTi theory ii^ not in bnr- 
mony with such a broad AA9iimption, tt onrrieA 
with it no <lcnial of tbc phenomenon of pha^ocyto- 
tis nor of iU importance iu certain inf«ction& 

From tliese ftcleetod considerations it i§ bmd 
thftt tlic two Ihcories do not fltand to earl) otlier in 
the rciatioQ of antitheses, and in the lii^bt of pre^r- 
eiut knovledgo it would »ecm unwarranled to cling 
to one view tt> tbft nliHtiliifi^ csohisintt of ibo other. 
It do« not follow thflt Ijec.iuse tlemonBtrflble 
«eriim properties otplnin immunity to ona diaea^o, 
Of to u i*i-rtain group iif iHii'iLM-*, that nvovi*ry 
from all diseases must depend on propertlta of tbc 
jacrumj nor because pbago^^'tie netivity (>xp1iLiiiii 
recovery in certain instances tbat reoovery from 
all diseases mu^t depend on n similar ad^irity. The 
coTiditiona which csist in each disoaflc, of eourso. 
rnuat be recognised independently, Tt so bsppcnc 
that recovery from a certain in"oup of diiensc*, 
e, ff„ staph tIococchs. etreptococciie and pnciimo- 
coceijB infef?Uons, is not accompanied by tlie de- 
Tplopmcnt of eonjtptcnou? nntitoxic or bactericMal 
propcrtica in tlic scrum, but they are chnracteriBcd 
by a great increase in tbe number of circiilating 
lencocjte* (mirropba^^), prUb of known pbat^ 
cytic and boctcncidal power, whcrcaa the opposite 
tonditiona ara faund in c^ertain other diseases, e- 
g., t^TihoSd and diphtheria. If one s«Ia the mnat 
apparent explanation in each case, the great letico- 

opsoyiys akd eerlicb's theory, sse 

cytoets would seem to be of prime importance in 
the first groupj and the antitoiic and hactericidal 
power of the serum in the second. 

Investigations from various sources render un- op-o»ii 
questionable the value of phagocytosis in certain 
infections^ and of particular significance is the 
work concerning opsonins which was referred to in 
the preceding chapter. From this work it follows 
that even for the phagocytic destruction of hue- 
teria the serum contains properties which are of 
essential importance. This appears of all the more 
importance from the fact that immunization with 
at least some micro-organisms (streptococcus, 
staphylococcus) causes an increase in opsonins or 
bacieriotropic substances. 

The accompanying illustration, with some modi- 
fications^ is taken from '*E)jrlich's Seiienketitn' 
theorie," by Ludvig Asclioff. The cell used for 
imraunization is assumed to be a cell which will 
cause the formation of antitoxin, agglutinin or 
precipitin, and bactericidal amboceptors ; the 
diphtheria bacillus is such an organism, consider- 
ing toxin as one of the receptors of the bacillus. 
This means that the bacillus is able to cause the 
overproduction of all three types of receptors. The 
illustration, however, is on the basis of a hypo- 
thetieal rell (p. 3C0). 

A list of immunizing bodies, their anti-bodies, 
and synonyms for complement and amboceptor, 
is also appendeil (p. 361). 


Lmror Ihhunizino Bodevi and Tretb ArrrisODiis. 

AatlgeiiBor Prodnctsof 
ImniaDlziiig I mmnnixn- 



□ as s u b - 

o DS :>Db' 



of bactVTift 
CsrCotoxLti pro- 


A □ t i c □ m pis' 




two bodlu, 
1- «„ compLfr 
D14P t aad 

Cjto toxins 





CTtDkulDii J BHCterloly^^ios 

ISpBolfl] Cyto- 
\_ toxins 

3p«rmo toxin 




sin^ «(c. 


AatlprKLiMtinfl /^ CoDsIstin^ efthflr ot BUtL- 

AntiHffffLiiCiDLnft ft) i complqmAnU or antlmm- 

Anticylotoxinfl I boceptOTS; tbe latter 

ADtihaiuoLjrslns. J may b« an antibcMly for 

ato. \ tbc CDrnplementapmlouB 

T or Tor tbs cytophllous 

I hftptopboraoT tba ambo- 

V captor- 



Z wiiTb e n lin r pe r 

IntermiidEary bcMly 

Sabatuice sangibilisatrica 






I'KiscirLKs OF ctrothehapy. 

In iIk atiit'l seuae ftcrothcrapv roeana the in- 
jection cf fflntJtoric or Aittibacterial sennns for 
curative or pvopliyiactic purpcees; tliH i» pflsaivc 
immiiniJCfltioii or *Ejrtfcl tf^roUierupy, Athve im- 
MttJTiiynTimt, in whir-h t\\p ti>uiU'8 of tli^ indlvtd- 
ufll are iuduced to form aatltoxina or anlilflctcriol 
Bubetouccf Qn a rcfult at vncciniition '-r pi-otectivo 
iiicH'ulntionit, inny Ijt con»i<Ierod a? inriirect eero- 
tJierapy. We nifly, tlicrcfore, include tbfl lattor as 
out! of ttic ttirotliorapeuUe meofturei, 

Bcnrin^ in mind the significance of the terms 
Actjs'o and pasBivc immanizatioD^ ftnd tbc f4Ct 
llmt Lhev may bo titled for euraliire ami prophyloG* 
lie purpoBCn, the Tarioii* procedures mny be clasa- 
fled aa followe:* 

l1llB>iltt^ltl La II 
uf Hrrirnirr- 


A* Aotivo iiomuiiiMtion, in which vnocina- 
l.jon and protective; iiineulHtions are iiielKded> ha 
with the org^ninnB of typhoid* cholera and plague. 
Depending on the matetiJil mjected. the rosnlt U 
the foriNalitMi of uiilitu^lns or anliniicrobit Kub' 
tftmiccri (nmbcceptcn) ; nggltitinizis nre formed ia- 

1. Inoculation of virulent orgaoIsniB. (a) In- 
Dcuktion with Email amounts of a virulent organ- 
iKm, L p., of a nm-fatrtl dosy; useil prindpally In 
experimental work, (ft) Inoculation with virulent 

• MfirtlSitrt from ll»oftPh anrt |f*hTrnanT«'l In "l*lt 

HfmmtHirAl'KLTlC liJCAHL-I^lC^, 


Or^stivsxns into ii tissiie which li«s some nttlurol re- 
Birtancc- The success of vftccinntion Againat atnnJl- 
po3C by uaing vims obtained directly from the dia- 
easeilj a methoil which waa praetitral ia earlitfr 
limce, wuG probably due to the fact that the rirud 
fourd unfflvorable coDditiore for the derdopm^nt 
of tindcuce ia the kkin. In somt ioatiiicea im- 
muniKBti^n in *iccomplis!iPil more f^uccci^sfiilly hv 
inociil&tiozi of bacteria or toiiiis into the blood 
str^sin, ofl m Kitfe method of vaocination against 
43rriitiloJ"iiLi<- iintlimji aad in iniitiuniKatimi with 
rattJciiTinkc venom. 

2. Injection of attenuated virus or toiUD. At- 
irrnnnti^ti nmy he sccomplished by nir itnd light 
(cl^ickcn-cholcrfl. PfLStciir) ; by caltivatioD at high 
temperatures (Aothrai^ Past€iir) ; by chemieal 
ngcnU (nntiiraXr Iloux; dtphtherja and tL-tnntia 
toxin?, Behring and Roux) ; by dcsiecation (rnbicB, 
Paateur) ; by pasaing the virua through other 
aniinab (swine eryaipcloa, Pat»teur) ^ Thiti loit 
obt^rvatioTi waa it moti iiKtruetivu one; pujfting 
the bucilluA tlirough tlie rabbit pcreral timre in- 
creased its rifulcnce for the rabbit but docreaeed it 
for awine, wliik* poking the orpinUm through Ihi* 
dove increased it« virulence for *wine. 

3. injection of killed org^nisma (nnthrai, Toua- 
aaint; *»iue. plnj^ue, Sdnifni acid SniUh). Thisi 
is the Kftfeat means of vaccinating agninat cholera, 
^r]Aoid and plague. Irt the Ptsteur treatn^cnt of 
hyidrophohifl tlif i\r>i injcrfirn uf Ibf ilried fjpinal 
coH probably oontiiiriB the Idllod virus. 

4. tnj^'tion of bacterial conatituema (a) Bacier- 
jal CE^II platm (Buchner^s pluiiniii, obtained by »iu1>- 
mittin^ micro-organi«ma to hi^h prefsure, and 
Koch's tuberculin TR); (6) Soltible bact^nl 




prurlutU (tlie Iwielenii) proteins, ad Kcwli'« old 
tuberclin and nuUIcin ; the Mluble toxifui ; 

prodnota of bacterial autolvfiis). Whep toxicu 
arc iiijctW niitiinxiris nre /ormcil- The 
antolytic products of Aon^e organJanifl. o. g«. 
tjplioid and dysootvry^ cntise the fonnatJoii of bac- 
tericjd&l amburrpioD* nnd ngglutlnins^ but not 

B. PiuuLTo immuniRfltion : tlie prophvlflctic in- 
jtfcliuii of antibacterial jtuj antitoxic becauia. 

C. Mixed Active wd pMsivc immunisation: the 
Bimultaneoua injection o( an inunune «omm with 
tli« coiTPspoading organUm, which may be killed 
or HvUij:. The scrum causes immediate, tlioujih 
tomporarr, r^fiifitance, and^ in the m^ntimo, ftn 
ktUvh, iximi? |M^rmjtiiFiit immujiity iWvclapa aa a 
conBequecoo of tbe injection ol tlie orga7i'jzn& 
Thii method hui; been practiced with e^ine plague, 
svine erjaipdus. rinderpest, and experi men tally 
in tjpboid, cholcrn ^n^ plagu«- 


A. Active immunir^tton. 

1. Injection of killed micre-orgamsmfi in small 
\\mm vn(h tht intenfinu of basE^ning antibody for* 
malioD* a« suggested by Praenkel in the treatment 
of typhoid ferer; ralue not yet demonstrated, 

B. PaftBive immi^iizatioQ. 

1. With antitoxic serams; diphtheria, teLouLa, 
make bites, plngLie, tiibcrcnlosiB {?), typhoid {?), 
streptococcus infection* (?), etc. 

2. With antibacterial serams; typhoid, cholera. 
plo^c, dysentery^ streptococcus (?), stapbylococ- 
cua (?) and pncnmococcita (?) infect]cm«. 

sTttaxuTii oy tji'uuiis. 


In general, floniTns to bo cfToctivc murt Jmvo a i.'in^rni 
certain Hireiigtli. When diphtlivriA autitoxtn wjui ftprnaiB. 
firet used prcparcihoDs were pul oa the marbot 
vhich conUint!d tntiilj or fewtT uuUtoxau vmtta 
per cubic ccEtimetcn a strength whicb would 
nwc£fiitato the iDJectioD ol 150 c.a. or more in or- 
der to iiilrodur^e 3,000 iinitfl^ Mudi ot Uie early 
criticiffm of diphthcrin ontitoiiin is trnccnbtc to the 
lev vaIuq of the i^ninis u£ed nt thnt time rathi;r 
lliAH to au iDJuiIoufi cfFiTcL ou the iiatienUn If 
diphthonft ontitoim nov/ contama Icaa than S5U 
unit* per c.e. it is considered unfit for ii*p; many 
4rrum» contnin 500 ot more unitp per cubic ceu- 

Aiitituiji' unci olhvr serums t^lioiild be Uee fnim 
micro-orjrnniams and toxins. The cosea of tctaiiu« 
which <3cvp|oped in St. Loiiis following the injec- 
tion of dtplitben& antitoxin will It:! rnncmheii-ih 
With correct goTCrnmentil anpeniflion of the 
mnnnfiUTlnrn ^f kctuius, such ncc't^tmia are entirply 
preron tabic.' 

For the sake of simplieit}' ve may eoiialdn' the 
prliiciplCA involved in wrnim therapy undnr ilre 
three topics of {c) antitoxinp, (6) bactoHcidoI or 
antibacterial aeruma, and (e) TBccTnatloD, 

It bci4 been siilSciently erupha^t^ed tTia( tieutraS- -tmlrvmiBi. 
isation of toxin by anUtoxtn implies a chemical 
tinion between tho two ftubctsnceai. When tho tvo 
arc iciixcd ciit»ii1c tl^c body «t n given tetaperatuiQ 
and &t a ^v^ concent ration^ the rapidity and com- 
pltlcueoB wjUi whidi tliL- union oc^turn drpnnxln 
only on the dcfcrcc of aitinity trhich one has for tbe 

I, ic«4<:b«plfrr XI (Pad 111 


ihF£CTwy A?iD iMyvyiry. 



otbor. There i« no tliir^ Bubetonce vitli vtiioh oat 
or tlie otlier mo)' iinile. In tliebodj^, bowevefj Uie 
coiiditjon* are more complex; in this cam two com* 
bmftUoiifl aro poeeibk for tho toxin, one with the 
aDlitoxin wlidj lias bttii iulnnIuc."tiJ ami a seconJ 
u'jlh Uio tiitfuc celia. Ag an instance of the great 
rapidilj with wliicli toxin may unite with C€Us, 
the work of HeyiJiaitA with tetunna toxiti may be 
CJtcd. ''Hevmoiia found that, if all the blood were 
rouiovod from an arLtmol a faw minutes nftor the 
injection of a aingle fatal doae of t^tanuti t^u 
taod tfao blood of anoUiOr oniinal sttbetituted, atill 
the animal died of l^taiiuit'' (Rikhie) ; that i« to 
uy, nil tlkC toxin h&d been bound by tbe cells in 
that brief time. 

Otiier ejiienmentn nlinw thai. quantiUes of tmlii 
and antitoxin wliich tire ncutreti when mixed bo- 
foro injection are not entirely iiPUtral if injectajl 
fleparatcl>' and al dilTcr^iit points of the body. In 
UjIb instance 6omo of the toxin lias hod time to 
unitt* with llsfin.' ceils before it could comv in con- 
tact with the antitoxin. 

Certain work by Donitx iltuetratee not only the 
rapidily witli which tonin iray be bound by the 
tit^mic, but also the method by which anntoxin ef- 
fect* n cute. In relation to tetanus he found thfll 
if the loiin were injected frat nnd the anlitoxin 
fotir minutes Inter, a qnnntity of antitoxin, which 
wnp flligbtly in ^XfO-HS of Hip inMitraJixing dow. woa 
re^iuired to prevent the development of tetanic 
■Tmptoma; if he waited eight minutesj six times 
n^ much ontitoviri: afrrr wixtwii miiJutcs. twelve 
timea am much: after one hour twenly-foiir timefl 
the simple noutrulixin^ doae wae requiml. A few 
hours later no amount of antitoxin eouM sjire the 

OV/tATiVE AOTiO?^ O^ HtJKliHi. 


nxumnU SimiUr conclitioiu were met in the ncu- 
trslizBtiou of dipbtberia toxin by its antitoxin in 
the body. MadH^n, in performing wliat he cttUed 
'^Curative Expenmenta iu Uic Iteagent tjUo*," 
found timt Uic: loug^ teUnolyciQ fiad been in con* 
tcict witli crvthroc/Ua, tlie more anutetauoljala 
wfljt roquirod to loar away the toxin from tho cor- 
puscli.-^. Practical BK[)erieiiD? wiUi i]iphth«ri& lUao 
mdicatce Lhct the longer the iliao^se laat* the more 
nntitoxin is roqmrcd for cure. 

The expeHments just eiLed give ua a cleur cun* 
ccpliou u to what is meant by the curfttive action 
of ftn untitoxio — an acUoji which coEfii^l* not of 
the ncuirali^.Ation uf Lbe circulating toxip, but of . 
the wresting awcy from the li^ue of the toxin 
which bos bt?en hound. I [leideuljil ly the einriilnt-* 
ing toxin is neutralized^ and for this step, which 
ifi euentialh' prophyUctie in nalitre, the- aiiDpl? 
ei]uivalciU of niitiloxin n ro^qmri^d. Bvtt for the 
wnvtmg of toxm from tissue eelte not a more 
M|nivaicnt of otLlitaxiii, but a greiit exrf-BS, is re- 
quired, as shown by the cipcrimente of Donits and 
of Madaon- 

Wliin diTihilii-'riii or U'taniu has advanced so far ?"'■"?* 
that no a^nount of antitoxin will cmjct a cure, the .taiian. 
relation of the toxin to the cvlU hiu become Mtntt- 
thing more tijan mere chemital uoiou, Furtlier 
proccsAC$ of n hiolo^^c or biochcmic mturc bavv fict 
in in which ihe toxin may have become an integral 
part of the proloplaam, und the luxopborouA K^^P 
may hate bn^n iU dotruclive action, whatever 
the nalnre of this action may be. 

It ia important to recognize tliai antitoxin can 
not repair tin inJLir>^ already done by the toxin. 
Tbe repair of the injury depends on the rc^ipen* 


ih'FKCTlOS A VU iMMVtitjy. 

tniftl t*rlii- 

live pover of the ndl*; hence, nutitojoB curcA by 
tearing from the oolU, p^hapfl Dot all, but ao much 
of the toxin tbat lees than a fata! ^JcBe remaSuft in 

tilt cell. 

W« nifty leam from the escpcnzneut^ of DdniU 
aud uf Hadseii Iwa imjwrtant principle* of anti- 
toxic therapy: Firet, tliat of early admin letratioo* 
i. e., before a ffttal amount of toxin hot bc«ii 
hoiiml, iitkI, secDJul, the iitccasity of injecUu^ miffi* 
cient quantities of antitoxin. 
. The comparative *tudy of diphtheria and tet- 

anus lift* clflTifloi^ tlie priiiriples of ^fititoxic 
ttierap3' to no small dcgroo. Knowing that diph* 
' \X\l't'u\ HiilLtoiin \\AA a iimeh greater L-uratJ\e T&lue 
tliaii tctnnun nntjtoxin^ wc find some conditions 
which would seem to exphiin t!jc diSoroDco, at 
lea^t \u part. 
Tersnnfi, Ju FC^'ard to tetanus wc havt* the following; 
farU" In the lesl-glasa th? flfliriity hctwrcn the 
toxin and antitoxin ia rather weak, since approxi* 
malely forty minutee are required for complete 
ne'iilrnliAnLion (Ehrlicli). On Llie uthtr Imrtd, tht 
experiment* of Donit/ nnd of Hcrmana 6how tJtat 
the affinity of the toxto for nervotig tiaine is tx- 
cwdin^V strong, all t!ie tosin being taken up 
witliin a few minutes. Thc^e two conditions alone 
■nggt^t thr prcbuliility of a low ciirntive valnp nn 
tlic pftrt of the scrum. Tlie tosin of tdanoa also 
has a remarkabld ael^tive aetion on the moat vital 
of al! oripinn^ the c^entrul nervous system ; lientrp, it 
lower crade of injury may prove fatal than in 
othpf inffH-t.ioTiH ui whirh lew important organs or 
those of greater reeupcrative power are iuvoivnd 
chicly. Furthijrmoro, it neeina (Meyer and Hon- 
som, Mfifie and Morsv) that the t^anua torn \f 



taken up by tlie nerve cndiuga and readies the 
j^nn^Uonic Cf^lle by way cf the iixis cyUntlcrKr 
wJiereas the antito:iiii which ie injeripd remflini* 
chjeflj in the blood nnd Jymiihatic circulHtions.. 
Hence, the toxin, to a c«rtaiD extent, ia isolntcd 
snd leffi sctwssihio to thcr action of the atititoxiu. 

Concerning Jipbtheria. the affinity betwMc i>ipi>iiirru< 
toxin nnd antitoxin is rektively strong, for com- 
jdete u^ulralixatiot in the tt^atr-gldBH inkes place in 
about HftcOD minutee (Khriich). On the oth«T 
hand, clinical exponence indicntes that the arTinity 
of diphdieria toiin fur tissue cdU i& less than tlint 
of totiuius toxin, for diphtheria may readily he 
nired on the secood or thinl day of the Hitsviw^r 
whereas a cure of tetaniiB ia rarely affected, Thcac 
would seeni to be Javorab!e conditions for siicreHR- 
ful scrvim therapy. Altiioiigh tbc toxin of <bph- 
theria may attack the ne^^'o^3 system, the paroly* 
aiaseen in ^iich ca^e^ is seldom fntah On thti hnaui 
of anatomic Endings in fatal ca«ca it seems prob- 
able that the gieater portion of the tovin ie faknn 
up hy porcndivmatona and lymphatic organa, and 
byconnecJivo tiunoc (animal eipenmente), tvliich 
compared with the ncttous lissue are ot \esf imme* 
dinte importanoo for lif« nnd have ^rreater rceupor- 
ntivf powpTK. W* mny infpr tmm cTiitieal ''Tppri- 
tnee that diphOicria toxin is bo situated in the 
body thst it it aceeaiible to the acb'on of the anti* 

W« have, thcrcforo, the followinjf faclora 
whtch npptir^fly are of Importance for the no i«"*nr^r, 
ecw of antifoxie therapy: 1. The concentration 
(ttren^h) of the ontitotin vhieh is injected. 2. 
Ill fre^oin from conlaminalion and advEmtltioua 
loxiDA. 3. The time of ib ftdminUtTotion. 4. The 




4|uaiittty injet^teO, 5- The dt^rue of idHnlt}' int* 
tween toiin and autitomi. C, Th* degree of affinitr 
helwoen toxin ard Hbsug (^Ws. T, The amount of 
liiiiiE w)ii<-Fi mny hn iHmml uithout il fnini iunir, at 
which tho >itai iiiiportoocc of the organs involTcd 
ninl thi^if Kcupuriitivt] power* an? fnotor*, 8, Tlie 
locution of the toxiti in the bo6y, \. c., tU ftccAni* 
bility for the Antitoxin. 
i»r4>phrUfii4< What hus been said reht«B to Uie curative ao- 
tion of oTititciTiii. It is evident that the ALlion i>f 
antitoxin, when lued ns a prophylactic, h of a 
fiimplcr nature, for in tliio inatimce the condllion^ 
approximate tJmee of th^ tesUiubp cxjicTimrnt, 
There has bpen opportunity for Uic antitoxin ti> 
become unlfbrmly distributed in the blood and 
lymphatic circulations; hence, it is able to meet 
and to bind the toxin before the Utter oomea in 
cfmtttct with the receptors of imjwrtant cells. The 
higb value of tctanua antitoxin as n prophylactie, 
u value vrhtch haa become evident in recent yenre, 
prohablv depends on this condition. 

The iinmnu]!}- which is olTorded by a prophy- 
liirLic iiijt*tion of antitoxin Is of short (liirntioii, 
from two to three weeks; the antitoxin n excreted 
in the urine to a coogiderable extent, but in part 
nmy he hotmd and awimilaled by the Lieeues. 

(») tt\<-n:K[riiiYr on .wTTTun'Kiii.tL jsetchms. 

na#i*vietiui Attention has been directed repeatedly to a 
Urge group of orgauiamB the toxic constituente of 
wiiich arc inlcgmlly Dssociated with tiie proto- 
plasTTi of ihe micrnbps; the toxie Bubstanoe* are 
endotoxins. Certain mcmhete of thin group, of 
whicli the typhoid, paratyphoid, eolon and dy«on- 
tery harillt and the vibrio of dioWa ore represent- 

or fhiuh. 



atives^ cauBs iliL' Jcvi^lopmemt of strong boclerici* 
dfll Bcrums in the immuniied fiDimal, Id Chaptef 
-\VJ^ A. it wa4 fliouri that fiieh sorumB bivc iio 
powFP of DeinraliKing the endoto^iina of th« «inv- 
sponding orgnniemB; liencc, vrhal^ver prophylnctic 
and curative propertiofi thej may hcve would eeom 
to (lepetid on the bacEerurrtla] action nf the ambo- 
ccplor-complnmcnt ccmplcx. As to wheflier the 
flubstftnccs whidi etimuUte phagocytoais, i. Oh, thff 
oji^uiiic or bacterlotropic suLgbuit-'CH are of imjiur- 
tantXf for the infrs t-ilam action of bootoricidal 
»ic'n:m«, rrmnins to be definitely cetoblishod. 

It is Gomiron knowledge that bactericidal 
MHinia have not beeu eucceeaful curative ogcnte, 
altliou^li in test-glass ejrperiineiil« tbr^ may \m 
able to kill I*ir(w numbers of orgftniams, Expcri- 
mfntal urork hnii hrnoght to light a mimber of coa- 
diti'ji^a which recidev their iiieiTecliip-mess some- 
what intelligible, but thi* knowledge hae been of 
litlle service in incrc^jiAing thrir value, and at thU 
moment their outlook ae curative agents is not rery 

Animal i-i peri men ti< indicate timl, pTophyladi- 
cully, the)- arr much more powerful thnn when 
iu^ flg curative agents. Ua fortunately. how«Tr>r, 
aa m the case of auLiloiIua. tie Imriiuiiity whidi U 
conferred 10 of abort duration, the aorum bcm^ ex- 
cnitixl or tin? nnliboclif« di'Htroyixl within two ^r 
tbrcc weeks. Vox this reason they are not auited 
for funeral prophylactic lise in man, bat thoy may 
b«* dirfiin:tly uwful when coiEibined witli vardnn- 
lion, att indicated hiter 

BactcHcidai Bertmia arc efncient in eavlnj^ ex- 
pennK'nt aniiraU, provided the vCrum \9 injected 
in advance M, fiimiiUnnoou^y with or rery diortly 

( ftrailw 

tiiocle Pol 

Tliiiw nt 


t\FscTwy A.yD i^tMvmfy. 

lit I viuplc- 

oftcr tlic bacterid arc introduced. By injecting 
the vibrio of oboler& and anticbolen wram aimnl- 
tai:»UHl> one may readily ftave a guiaea-pig from 
ten timcA tho fatnl iloee» or more. If thu oulture 
bp injwlrd first ^ti<] the scrKm Intrr n Urgrr 
atnount of ficmm ia rcqmred to 9ave tbe animaL 
After a few hours s BUlficient amount of sflnun to 
kill nil the xjbnua ina,v be iujcclcil, yet tbu ani- 
mal m\\ die from the action of the endotoxins 
which liave beeij liberfllpH. T^e orgflriama bnd 
proliferated to such «ij extent tHat the maaa. 
though de!ad, contjiin&d a fatul iLii]<>unt of ondo- 
toiitJ. A «tatc;menl nindp prr'\i^u«]y may be r9- 
peatedf tbat tbe admimstratioi: of a baotoriddal 
MTum rQliiGr tlian beiog benellctaV may actually be 
icjurioiia> iQ that it disaolves the micro-organism* 
rapidly, theivby liberaiirg aa exrsujve amount of 
fUilotojuin. Ihis, porliap?, is aoi deflntlaly eaUV 
liabcd aa a point of practical importaaicc. 

Hamf* deiermintid the oiuount oE a bactencidal 
M'titai v/hu-h ii able to bhvl' a guitiea-pig Trum an 
incipient infection, one may calculate on the basa 
of weight ihi? amount whJoh would be required to 
MiTt a mail um3rr Mir mtiirr comliiions; frtqui*iitlj 
it nmounts to impowJblc quantities, hundreds of 
cubic ecntinieler?. The conditiona are all the less 
promising when we remember that physioion* are 
u^allj oflTied on to treat vell-efftabliehed rather 
than iDcipient infectiona. 

Other conditions which operate against tbe cf- 
fectivonMa of bncterJddal BOrunta oe ourative 
agents have to do with peculiaril i(*s of compliv 
monta and oinhoceptore. The labilth' of complc- 
mrot involvea certain diflirulties, A bftctericidal 
serum. «e ono would purchase it. containa none. 

/MTiU.iCTi^HJXL sfiecus. 


because uf ite spojjfaneona Jegeuvratiaii- Tlieo- 
rcticaJiy. this diUiculty mAv be al>viated ill thre« 
vnyt: Fimt, ore may lite serums which lire trt^i 
from the immUDir^ml ^kniciLal : second, one may oocn- 
plomeut Uio BoIutioD of amboccptore (old immiino 
Etertun) by Uie HtUUlioii of frtsh sRraen frotn n uor- 
mal animnl ^hich is known to contain suiUblc 
cfvnplpment; or, t^iird, on^ may inject the eompli?* 
meat-free 6enint and place teliance on the comply 
mcnt which eiiets m the plusma and lymph ot tho 
[uilieut for uctivntion Df the umbocepiors. It i» 
eufficicnUy cet.abliahed that none of these procc* 
rliircG (!iihano^ the curative value of the serums to 
a eatiefactory eitent* 

Eogardleas oi the ajnouiit of foreign oompl*^ 
lueut vfWidA IM itrirotliii.'M'd, it nppp«r* in hr ill* 
Fertcd from its function, It haa been ebown ci- 
perimentally tlial tho tisfiue* fnay abaoib a foreigo 
CDinplemcnl, aud tlic iinrre Tact that nnticomple* 
mtrnU arc lormctl i=o readily indicflloe that comple- 
ment may he bniind by the tid^ies. fn accordancp 
vrith a rather gcncraJ principU, if the ammal 
vrhich fjpniabcK iho »erum U remote from mau 
lolilogif^ally Ihtrr lh a]| tlie ml>^F^ likclihrNid of th? 
complement being fliod by human tiseuee* 

It haa b«cn tuggested that if one ahould ohooae 
for immrniixatioii anisialfl M'hich nro closely re* 
lated to man, a£ ehimpanzeoa &nd monkeye. a 
double adianta^e would he i^abied : Finl^ the for- 
cijCTi complement mity be identical or pimilnr to 
that in man and consequently wotiM bd lecB Hkoly 
to be absorbed by Uie tissues; and. second, tl^ie 
complcmcutophiloua haptophores of the ambocep- 
tors may be »o catiitnictod thut humiui comple* 
meiit voutd Berre for activation. Tboor^ticaUy. 

IIICBl b>- 

1 hflirr Ot 
fur IvKiiual 


rSFECTIOS litffi iUMVyiTY. 

tit ■«■*(■ Vkkl 111 I- 
IfT- tif Ml- 

the conHitiouB ivoiilrl be H<^l if immune human 
srnjm w«Tp ftxflilnble for thnrnpentic puqwuea. 

If one dtpenJa on the complement in the pa- 
Utntfi bo<ly for aetivatioii of tlie amboceptors, 
tlicrt' ore Iwo |Mis«iblB tlifficullies of iicporlanee: 
rirfit, the native compIcmGut of the body is oft€ii 
^*crcssed iJuring infections and in some chronie 
ttiseosea an^l may be too little for tliorou^ activa- 
tion; aoconiJ, ihe aniboccplora of the immune 
geriim may demand for Iheir flcKvutiou a uomjjle- 
ment or eoTnplemcnte wbieh the boily docs not eon- 

Divereion of complement hafi been referred to a« 
a phenomenon si?«n in te^t-txjbe eiiaeriments. In 
thiF^ coiiditioti an e.\<:i.'ss of nmboeej)1tirs iu iwtmtf 
way dccrcQ«a the power of the scrum; by an ex- 
cess of amboeeplor^ ^ne menns. in this instanee^ 
Kiu;b a, t\Mii\\W\.y i\mi iciuuy ^rc unbound hy IliC 
bacteria. It ia auppoaod that a certnin amount of 
111* complement is absorbed by free or unbound 
nmbftceptor*. hence the effect is like that of too 
little complements In tho desire to ndminifiter a 
sulVieient amcimt of anlibodies. so mncb may be 
introduced that diversion of the complemffnt Of^ 
cnrs in the body. Results obtained by Loffler and 
Able, by Pfeiffer and \iy Bniton Hiid ulberR, in 
which cxcrs9i;'c dosca of immune ncnim were lea* 
proleotiire llinn moderate doses, ahow that a Bimi- 
Jnr phenomenon ocaira in the body. 

In cortflin diEcafteg the microbes are so aituat«d 
Oiat a sfirnm \v& ordinarily nihninistiTeil may not 
be able to reach them. Pfciffer thinka that there 
is little hope for the serum treatment of cholera 
becBuse of ibe e^tclnaive location of the living ar- 
gonisma in the intestinal tract. In typhoid also 

A ynBACTEHjA L HF.itnax. 

Uie inteatjnefi arg a reservoir of tvplio)<3 biieiUt, 
alUiOTigh the tiring Drganisms reach the circuln* 
tion in abundance, 

liy Mjiy of Bummary, the following conditionB 
appcnr nji factors in tlic low cnrativo I'alue of bac- 
tmctrlsl seniTTiB: 1^ Baot^ricidat sertirag are not 
ftnti toxic. 2, They may tibtrafr an exceAsive 
amount of vuiSotoxin by dlseolring the bacteria^ 3> 
THp lability of exogcnouB complerattit- 4. Tlie 
power of tlie tiaaiica to abaoi-b tbe cornplemeuta of 
a foreign acrum. 6. TIig lack of ti sufHcicnt 
ftraonnt of suitable cnrnplcm^nt in tbe humoii 
body. (), The difiicuIW of obtaining amboceptort 
for which humiin compIenienU arc s^iiUk!- 7. The 
pc»«ibility nf tliverBiori cf compIeniRnt by an ei- 
ceaa of auiboccptora. 8> Inaccessibility of ihc 
micTfM3r(innf}imA in certain iufuetiouA (ehol^ra, 

Aa pointed out elsewhere, another group of or- 
ganisms, the mcmbcre o£ vhich contain cndo- 
toxinCf causes tho formation neither of nntitoxinii 
nor of badirrificlal aerurns; slreptocoozus, sLaphy- 
locoocua, pmeumococcufl^ etc. Many inrcfitlgatora, 
neverthclcw, ore pofiitivo in their claima that the 
ontiacnim* for theee organisms have a protective 
and iTtrn a cnrative vahii>. The projierLit^'jt on whitih 
their ralac depen<]6 have not been satiBradorily 
a3certained. Although certain antiBtrcptocoocua 
senima sht unii^ to he (tntiloxic, it is contrndptl by 
othmv that thry art hy Ktlinnlnling phngcicytciua. 
ft hfljt born ^liown that immuniEahoM with thete 
oTf^aninna t-H^tses an increa^i^ m ihe dp^ontns- 
Thfir cnrnCiv^ value U ver^' low ii^ e\pon]iieutil 
vork and they fait totally \t injected a few hoora 

Otb«<r "Anil 



r:frtVTtoy a\d rvntrsny. 



lubwqiicnt Ic tlie introdudioq nf U^« orKauiaius. 
CHmcally, uo trt familitr with tlinn oa fmhiTct. 
It is pnrticulsrly in relation to tJie stre|>locoo* 
CU8 thftl th« eo-callcd poI^r'^'^J^t «eruma have been 
prepared. Coll tire* ot ulrc-ptococouf obtained 
from tiuEiLcroua sources Lit uacd id the immumiui* 
tioD mth the expectation tt&t th« £i?rum will ba 
elTective agMinst varioua slraiDS of alreptoooccL 
Tltc prineipLc may be an impcrtaut ouc in the 
proparntion of oUi«r antibncteriul Jind bactericidal 

W*: nri* xmisl familiwr wit!i the terms iraccinft 
and vnccinntion 04 applied to prclectivL* iuouula* 
tion againsc smallpox. Thev iire luwl, howp\Tr, 
vith equal propnely in all inataDCca in vrhicli the 
sttonuated or killeil rinia of a disease is Inoculated 
For the purpo^ of eetablishin^ ressiatancc to on 
infccUou. Jho proceed sot in motion by vaccina- 
tion in ona of active immunisation in whicU the 
r(H» art induced to form eipecific antibodies over a 
lon^' [Jtriod; henc^ the re*islttQ^e ia more pro* 
k.'uted tlLan tliat cBlablibired by i»a«bjve immnui- 


Crxitihi expert 111 ea tell wurk^ as previously etatfid, 
itidicatci; that the aequired rcsisLaiK-c per£E£ls after 
t}i*» ffirmiiiion of nrittl>Gdics hns ceaaerl, evim after 
the quantity of the Inttcr has 8unk to the normoJ. 
Tliia condition has been fliplfltned by aaftuming 
(Tial, aa a consequeuce of vaecinaticu, the edU of 
the body hnve been "trained" to produce the coav 
responding ret!eplor«; hrncp, when tho micTO-ot^ 
fanjams gain entrance ot a subsequent time nevr 
antibodies are formed ao rapidly and in audi abun- 
dance that the ineipient infection ie oy«Komc. 

xKGArnji Anv t^itsTivJA i'H^«uv«. an 

Tn Bom^ iriBlsnces Mie nutiirc of Hio viru* mcA 
10 unknovD, as in smallpox ^ad hydrophobia: io 
all probability, Imvewr, it eunHthU of mfcro^r* 
gaiuAins rather ihtit of toxins alone. Jn the csac 
of trphoid, cholera, pla^e and other diseodea ol 
knowu t^Liolo^'v puci^ r^tllurc-H, living or killed, aro 
inoculated. I'l-utccLLon rloc« not follow jmrncdi- 
aicly on the ioociiUtion. We are BulTioienlly fa- 
mllUr with tlila fact Jn relatlua iiy ^[nalipox, in 
wliich ocverot daya arc rociuircd for the formation 
of a prDtecI.ivp amount of Ihr nntihndir*. Thnn? 
is rcaflon to believe that the interval between the 
inoctdatiou and the appearance of antihodies la 
chiirftderin>l hy n ih^rtiJUH^l rtHiRLniiriT ou Uii* part 
of the individual, ao that during this brief period 
he ia tumanallj auEcepHble to infection. 

That periixl iinitied lately following the injec- J**Ji',^*p* *"* 
tion of A toxin or microbe, in which the quantity rhn^-. 
of antitiodiwi im^erjfOP* a Umpcniry di^rcaM, 
Wright Fpccka of a« the negative phase of the iiu* 
mutiiaation ; whtyrea* that period marked by the 
new fonufltiuu of milibodir'n ix caillwl Ihp punitive 
p}uu& The ncf:ati\<c phaac laata from a day or 
two to wv(T8l da}"s, dcpi>ntling on the quantity and 
natnre of the vinia injected (typhoid), A uixmd 
injection tihouM nut bo Riven <!urirjf: the ncBotivc 
phnm. »in(*e it ranfiw » fwrtber decrpase in the 
antibodies and proloap t!ie plrnae, Wright apoalo 
of this QJi A cumulative n<^tivc pbnfle. A cumu* 
lative positive phd^. Eiinrked by the fonnation of 
larger amounhi of antibodin, may be induced by 
the proper spacing of a namber of injections- 

In certain Inatancee the nntnre of 1h« anti* 
bodies i»» known, Tn typhoid, cholera, plague and 
dyienlery* for eiamplcr, lh*y conauit of bactericidal 




amboceptors; sgglutlniiu and |)nfMpiUn!& are 
fonoed inciilcntAlLy. The wnbfvccptora nntiirnllv 

ffpporifl on thf» ramplomiTnt of tht? hotly for th«r 
activation. If tltc <lisea&e 10 one of uiikiiovr^i etiol* 
CKy the uulurc of tbc nntibo^iire is not easily do- 
(DrniiaH- \V> hIiouM keep lu mlod tlie poftaibiU 
ity that vaccination may cauae aii iucreawj of tli^ 
opfiontns aDd l}iat thu potontia! ph&goc>'to«ia miLr 
Ihi-rebv lnn-omi? g^n^nfcr. 

In case the: incubation |Wriod of the vaccination 
i^ fihortcr ilmn tlint of the dijecase (EianllpoE^ hy* 
drdpl^oliia) vumnution Lisually h siicccssf j1 even if 
practiced vitliin s limitod titii« aft<^ cjcpoBuro to 

Vaccipaliuii iij iuJi\ulua] diseaaea ia con&Jdcrcd 
m Part 1 1- 

Tlicoretieftllv it would be poaeible to immnmM 
mnii ngainflt diplithcnn ami tcrtaitUB by inoculating 
with fluiall smounta'of tho correeponding toxins. 
Sucli a pr3ceiiuTe, for obvioas rwtftona, would bo 
unnecL-Mary and unjushfiabk. 

it ia not imhkdy that mixed active and passive 
immiiniKntiou «i!] Iw of great service in some in- 
fcctionan A ^ucct-^vfuL campaign ag&inat ri&der- 
p«^ baa tM^n onrrind on in tho Fhilippiuca by thiA 
luelliod. Iha blood of infected cattle contaiiis the 
vinu, which as yet has not been cultivated artifi- 
cially. The ^'runi t>f cattle whicli Imve recovered 
from the dieonse, or whicli liave been immtuiised 
cautiously vitli irf«^ted Mood, contalDs the apeci- 
lic Hutibudies. Both the iimn^um scrtim and viru- 
lent Wood ore used for Uie inooulatione. The aame 
primpl« has been found elTective iu expt'rimontal 
vork witli choJcra, typhoid and plague. Inimedi- 
ato immunity ia estsblubeil by the serum, which 

VLHATilK lAtViJi^JtrJOh, 


would dfmiTiate the duigor period mentioned 

abuvo, and before tho MmD diMppeam cmtirclj 
Retire immnnity ijPTelops, 

Wright, fclluwiij^ liiH diHenulIoiia on fin- viitiu' 
tioDB in opFonJc fKiwi-r nf Ihr Herum in different 
inCfctioTiH. coii'^liirlfii tlist in ferlain locdiied 
cliTOliic iiif^ttiLJiin »ucU ii;i rlironii' KUppiiniljvR 
praoom^ tbv body m a v-hob did ml i^apontl to 
Ui« InfMion with Hit' production f>f fintirHidii?«. 
Tlie iiTJOL'Liun of dead lioiujlogoutv t^r^AniHiii^ whh 
llicrcforc ri'Torlcd to in ordi^r, in thi? w^rrls of 
Wrijibi! "To cAploil in tliP iiil(>i^^1« or Hi* in* 
fecti^d tJAfiieit, the unexerc-ized immunising rapap- 
ilif* of the nninfrcte-d liwuic*." 

The <lodUf;e cf ihc injwtixl vaeeine wns t\*'- 
lOTmined flfrorHinji to rlip piTrpn^P of minfl Hie 
minimTim qtmritity uliic-h vrotiTij rcvtilt in tbe 
mnximum reapons*? f*f llir uninfected tiasut* ^ith 
the leset develDpnient of the so-onlled negative 
phnw. In ordi-r itt nKiiliitr Ihr fti^r^nntcy and 
4{js« of ttic therafwutic? inocjnhtionp. Wright ninilp 
use of oiMonic index ^^^timntioriF. 

Vorcine* »r^ preparpd u^ follows: 

Tlie rJpAired uTgnni^ni is ^rnn-ji on a auitible 
Kilid mctlium a^ an njijir ^Innt or hlnod »crnin 
fllailt for till? niininiiiiii titii« required for u g^^ 
growth, lULimflr CWimty-fi»ur hour». 

Suit Mihititiu i^ Uivu jliMihI In the i^lant, n fen 
cubic ceotiTJielcra arc tiauatlv tmflicient for iw 
*>' growti^ (Ih*^ 4^iunlit> need not l>e eiacl), 
und thr rnllzin? Hra[H*d nff inti llir mil soTutiim 
vith a sterile £la» rod or platimim loop. Tlic 
number of baHena x^cr eubje centimeter U (hen 
e^iirinted bT mUin^ v^ual volnmcft of dcflbrinnlcd 




/iVfjscr/oy axd ivAtvytfY. 

dtiil Miicuriii^ rjji u t\'u]c. Thr dilution nhoulil Ins 
ahont tlvo liinc-^. Tho roHhod of m^aftuniij!: ftqiinl 
ftntflll vnluni«s by njean^ of tapilltry tiil>«i a 
giMm in Chapkr XIX. vnnv be need ond a 
Hainan o^v.^ki etatn used lor fctnioiD^. 

SifK't.' Ili4- nirmbiT r>f i'ihr[iiiH'l4><( in |j(^riiin1 
hiimnn triood ie Abont ^.OOO.QOO, by a compamon 
of i\w nuTiib<.T of tiActonji xiilh th« number of 
I'm'jiMwlt'* Till* numlirr «f lmr|(*rm prr iriibic rim- 
liirtc'tot- ctm bf* rcadiW c&tiniatGd. By dilution Hilh 
•alt solution tbc n>i^uiri-^d doinj^n per cubic ccn- 
iimeUir niiiy be obtaineil. When it ie necessanr to 
keep the \0ccine a amaU nmoiuii of tri-^reaol (.2 
ptr Gont,) may bo nddod. 

ntieiitK tlieraptiilie iuiK-ulfllMia* hnia W» iiM^d 
for a,fin»t Tnnctr of infection*, both ncutc fliid 
chn^nic, and to botb locfil and sjetemit? infeotione. 
Kdilurttlly^ Ibc rtMiltx have n\w vntlnl wilhiii ividr 

In caso of cliTotkio localiired infwHons tbe 
thefrrrtiml WU for iUr ii*c of vacdncjt rcrnn 
plain. As pointed out by Theobald Smith: ''The 
eff'^rfiTi^rii'*;* of vjkvihiIh ^pplW in tbi> t^oiirw^ of 
aculc febrile di»cfiM:#, siioh 0* l.'i-phoid fever and 
pneiimonifl miiEt l>o aecnuntod for by principled of 
wbicb t'\pt*ri(iu'iil»il nirditine Imx n* v«'t nu ilrf^niLif 
knott'lcijpc." Thi^fiix- tic ally no aivnntagt can be 
expei-^ed from ndOin^ loxin* in an already over- 
intDJ[irat«l rn«'. 

This criliciflm doM wot apply, of cour»c, to flucli 
ft proetdiirc a^ U ttijigestcd by itoa&»ov, (Soo cbap- 
tw 00 i'lieHmonia.) 



AtteDtioD lias already been caltod to the fact 
that ao individual may be more susceptible to 
infections at one time than at another through 
various accidental conditions, as exposure and 
eshaufition. This, however, is not a specific hyper- 
Busceptibility and is usually more or kss transient. 

In contrast to this accidental condition^ stands 
a . specific susceptibility which is now comnionly 
knoAti) as anaphylaxis. The condition of the in- 
dividual or animal is spoken of by V. Pirquet as 
aliergv- (Allergie), a word which conveys the idea 
of an altered power of reaction on the part of the 
animal body, 

V. Pirquet's conception of allergy is best de- 
scribed in his own words, in which he uses vac- 
cination and revBCcination as an illustration. 
^'Vaccinia^ with which we can at any time institute 
an infection^ is just as much an infectious disease 
as is variola, of which it represents an attenuated 
form. Let us inoculate one person who was 
vaccinated two years previously and who, accord- 
ing to the customary view, is immune, with a 
drop of lymph. Then inoculate another who has 
not gone through tliis process and attend it 
closely. Xow will the immune person show ab- 
Rolulely nothing? On ihe contrary, when we re- 
turn after 24 hours, we find in the one who 
received his first inoculation (the normal person), 
a small crust showing no reaction, while in the 



immune there ie a norcjal small, raiB«d> anflam^ 
TTifltory, itcTiing, hyporemio ftrra. 

"f* Uit one jirttjuHnlj iiini^iitntril^ Ihercfure, 
hypcr*^i9ccptible ? Jf vc wait a few days tlifl 
pi<^tUT4i diaiip«>: Thfl papulo bct'omog brovnUh 
and Etmaller. wliUr hi llirr chm- of l)i(« fiivl vdtrt'iuu* 
tiOD, a ire^Icle forma under Ibe crunt, wliicli in- 
crCBMit more and more, becomes ^iirroundf'd b> a 
wide itmCf and louda to u ptuttulc- Now we mnst 
toudude tlkflt Die tmc n<i-i*i\ui^ hla fimt inw-u* 
Jfltioa h tJie more fluaecptible. since lie haa f6\-cr, 
|»in, find fl marked local iiiflunmdtioD> while in 
lW immune jif-Tvon nlgnii of infection hav^ loog 
fintr diiiK|jjHrrir4-d, 

"As it iippcATi lo mc both individiMla have 
reacted: Tlic oue earlier, tlic oihiT luler; one 
vitb A papule, tbe other with a puaiulo. In one 
the reiK^tion was lianlly noticeabler in the other 
pronounced. Through the prcviona inoculation 
no immunity in the eonw of inmeccpHbility hai 
derdoped, but it it only tht Ability to ivnt't uliieh 
hfls dinriiffftl, sntl *hi* in point of time, equality, 
8I11I ijunntitj." 

The condition then nppcnr« to be n paradoxical 
one, in ihat we have a certain degree of hyper- 
6UecepTJhiljt> in a patron vibo is rt-ally immune 
and hifi immunitir may rlepond to u grciitc-r ur 
leM degree on his ahility to K'flct qnirkly to the 
prcMnce of the infection* agent btforc the latter 
ha« time to proliferait (xicn?i\ch\ 

PoHier and Eichct, m liHJ"^, oWrvcd a peeuliftT 
hdiavior on the pnit of n poUon found in wrtafn 



Tha poJiiion was inx^riibly faUl for dr^gA tfh4>ii 
^ven M » flfif iiijV-Llina in duift'a nf C.B gni. \yei- 
kilosnim uf rtntmnl w«i^ht, \t\ii wua rarely falttl 
in i^opoa ol nadcr Oj^ j^n. per kilojnnip. Pcath 
tiGimllv n^cniTpil in from Umr to ninn Hav*, Whpn 
H H'l-tiiirl tlivip, ^Hiwi-vrr, wjiH ^ivcn to nn Hiiimnl 
rtliich liMil nM'overp<l from Oic firtt inj<.v1loii, 
deatli !i]pcrvcnc(3 ia n ?IJorl time, usually withiQ 
two dM ihroc qiinrl^Ts honm. The ^r^t injoction 
cvModUt modilic^il tlic n>MRtaTtcp of th<t animnl in 
EnnH" wav to thnl it liprnmp mnre fiiT*rrptihl*? tn 
ihc jrtiiHiin llinn il wah iii t\w flr>i inhiunrr. It 
iva« ti> thi? modified »tatc of the animar« rcmet- 
niicr tliiit Ificlii^l nppli'^fl llic numc "'anflphyiftji*/' 
wli]*h "-tunilw in roiitruKl t« a romliiion t>f pro- 


in llt03. Arlhu!* ob«.-rve(! l\m\, when rabbit.-^ t-iiin-- ft.* 
hiKl rcn-ivcd MVi^ial injuction^ of Unew sernim nt 
iTilf'Tvalt of s^'Tpfnl rlflVi, th* ieTum fi?awd to lx» 
jitjciirbcil n« h1 ftrM and tlisl then? r^^ulled locat 
necrosis and ofteo »loiiEhiDj^ iwiEU 9Qbsac|ucnt ulcer 

In ll*Ui, Thi^balil Smith toI*l Ehrlich of a ii.nMM.i.i 
phi' nuiiti^ null whieh tio had ahiEt^rv^il vhilc t^Jitin^ i>hVn->m«iivi 
th(? poti'HL'v «f ilipldlu'tirt aiililciiiri nn icniitrji- 
|>ip<- Animals whifh Iind received mjectioni of 
intitoitic hor»t !«Tiiiti nnd Int^r wit injected witli 
a amall ^itianlity of normal hrtrte >enim becwmo 
aeiitely ill or di«!, 

Ill i)w fiMvi\'tti)! yi-ir, 130.'*. u[i|ii-iiTrrl thi* nr- 
tirle9 of Oltf), Ro9<nnu and Antlerm^n, and of t. 
Piri)iitl a&d Sehiek. Bince thi^fc articlea in 
I'noniuiiiA amount of vark haft kc«n dnnc to ccf* 


nrisvTiOK AXD iMuvynr, 

tvUt« the pheDomena of ariRphylaTii iritli olliei 
propeww of iTHniunitj, 

I^ikc other proi'i^j^v of irrimtiuity nnaphyliXH 
mny be clA^iflpiT ntt nnUir^l and fte<|ii)r<Hl; andf 
ft^aiu. HL'ijtiiit-i] uurtiilivlail!- timy be actite, lU 
v'hich the proccf^ trnult^ from a rcnrtinn an the 
pari oi the tissue celts, or may he paeslvo — reeult- 
ing from thir iatimlurlion ot rrniljr-mndr nub' 
fltancc8 into the body, 

Hui'witx, Si'liuriL-lJ. Di>i.'m aiiO Mhtra, uerlaiu iu- 
clifidiula Are nnuMially effected bv the injttMtion 
of «ggA. orftbs. nesh, pork, olo, Tli« Kymptonos 
Rie variailp, but llitre l»i ofl^n it:4ii:^a, fi?ver, colic, 
am) rxnntlicmatn. It !?■ of conrw to br <iu«»tioae<] 
aa to whotiiOT savh livper^TisoGptibility is renllr 
iiaturnl nr nnfuiiyd by nirly KrnKitiyulirai, Hvho- 
field reports >uch a tM«: of bj|it-r»m»oi'ptihilify to 
egg which di^fpcercd after i^cpcotod increagio^ 
doacft of egg tnk«a in pillR^ uriiig tninuto amounts 
Irif be^iri wIlli. Sudi byperr^iiSL't-jitihilily baA lit^rn 
\*mg known imclcr the rmmc idio^vncracy. The 
idiojiynoracioK lo protaini, bow^^vcrf «boiiId be di*- 
tinguislied froiTL tttottd In vbir-h krtavzi chemica] 
nuhcrtance^* nnh at mercury or fnlicvlic Ocid. arc 

\fi\ve ntiflphylstifi lia^ bwr Fhidie*! in 9 tariety 
of maiimiahi and fouU, and sabatnnciaa vrhlth 
C'orreepond to tboeo concvmod iu imniuniEation 
have bMFL demorutratiHl. 

II will be vavW to lake up ihr^r vuruMis fai-lurfl, 
and After a di«cuB»inn of their nature, it hIII be 
caviar to underftiand llie llieorioi^ c^onoernins Th« 
niecluLiiLiiii of i}mt nrtioiu 



ceiled tie name of finHpltirTAi-t%-oik^ m sieiiHlbili- 
anogoti. ftad may be defined ab unr buLatano? 
whi^, irhcn Ukco inU the body, produocs a 
specific h)-jn>n!U»o*'ptJbtlih, ubusIK- after an iDCU- 
bation pprioil nf nt len*t tvntn fivp to i=even dayi, 

Thi^ Milwtiiiu-e* which hnvr bi?*?n dcmomfratfKl 
to «ct iiM iuifl])li>lMrLo^(?:nii nri? pioi<;ir» OT «r« in- 
BCpsnblj conncctMl witii prctcin^, 1'h«t «Qnp1ij- 
Ilctojp^nft nrc clowly rclntinl. or^ a« Kncdbcrj^cr, 
Doerr, and othcnt Uiink, id^utical with thoto 
hodint whieli prodiiL-i> 4^ompT<*rni^Dt dovlntlon, anti- 
Ixjdicjt, and ptci:ipitiiift, in thovn by tljc fact that 
ihe same aubstaDCCfi produce all (hreo phci^omcna' 
lliue, afl with prccipitinogpna wo have ail annphy- 
Iftii? ppeciflc for Fppriiw and fttr tiw»iiPK. Th« 
wime Iwipji whir-li arc njyririt: for prrtipflin for- 
mation. crytaJliDc icc*^ ^pcmiatozoa. and placenta, 
alfto ^v« A specific dnaphyUxii, while tliOK titfuea 
ffiioh «« kidot\\% liter, t:i^., alitch pioduet? only 
H(iti.^ii?« :ijKcifir prti-'ipiliim pruiluop H^jeL'ira ppmfie 
aiiaphylajiM, Aa an e:tctrptii:ra to ihU rule, it tEiay 
be nioDtioned that WOII0 does not find that iodised 
albLiiiiin produoea snaphyUxie tpcciCc for iodized 
albuiniiia rather than jperiea apeHfIc rMctJona, aa 
waa fouui) for precipiltna hy Oberniayer and Pick. 

One of Ibc firti qLieftioiiv whii^li arfflrc concern- Q«i«tJ4ii 
ing Tbeobald Smith'* phcnoimPDon M-ng thai of Ihr roaiaitr. 
relation of the anaphytacto^'cn to the diphthem 
toiUi and antitoxin, (n thii r*«?, \h& titiploytiicnt 
of tkonnal honv wruiu lendiU ulitiwtil tFiut an* 
a^kjdajDS vaa indapeDdent of Uie diplitlu^ria bacil* ' 
Ina darivat)re« and antitoxin prefciit in the torEina- 

ISrKCTH}S AXD 12i3tU^-tTr. 

Soinowhit more diflksult is the quertioc regard- 
ing Ihc pritrary toxicitj of such subptancea as aw 
oontained in o«l eeninL, vanoua phytalbuiQtuA and 
boctcriLi, ]£ ]tn« bcon fJiomi by Doorr rtcd Bau- 
bilscliek tiiat by liealing or by ttcidlfjing rbI K-rum 
it 14 poiesiblc lo remove the primnry tonicity with' 
out iAkin^r Hway the property of protlumg aoaphv- 
laAt»- Tn a nmilnr wny it ha« been i^honii by 
JJoEonau and Anderaort, Voughon, and otbera, tliflt 
bacterial proteins tree /rotn ioxic action can pro- 
flucrtt nnujihylasEU. Il has oha bcf^n shf^vn tbnt 
vhcreas id primarily toxic serum tlio lui-gcr the 
doFo the greater tho toxicit)*, in aoaphylaxis ?aaei- 
tiKatioii smaUcr doses Eeiisiti^e more readily Uiau 
largo nncF. 

That hypcrfLtftccptibiliiy to triip tonns does* oc- 
eur» howuvor^ liaa bocn demons Ira ted In the i-tic of 
diphibam torio and tetanua tosir. The phe- 
Domena here, however, arc distinct from anaphy- 
laxia in tho fact that tlie incnbation period in 
flhurnl, thut the eymptcmK come on gradimlly after 
the Becoiid dc»c, and [afltly, that after a certain 
length of time whic'h corroflponda to tho incuba- 
tion tiino of n Tin phyla HI* J inimiinily or decrease In 
auft^eptibility, m^uurw m coatraai to anapbylaJiis, 
Wo muat coDcinde, then, that toxicity and eenai- 
tizing propertioe are distinct from each cther- 

The flrmphylnct(j^(*n t-mni** inio roii*tcli*nilion in 
the priiiiury or wnBilltiii^ Jose and in tbt aecond- 
ary or toxic iJo*c. Mniy experiment* have bwn 
eorricd out lo determiae wheth<>p or not thc^ w-n- 
aitixiu^ and toxic action ort- dcpcndeui on the 
§amn )Tuhrlanc« or aimilar qualiUca of the same 
aub^tanee. Jt wfl« fonnd, for in^tanc^, tliat in the 

SK^ftiTJX'ATIOlf A^U 'lOSWiJy. 


cw^ ol' egg albumin nito twenty milliontVi of n 
fnum c^ulliced for aoEiditir^tion (WdU), iiiid about 
on^ thfliitflml timoc Hint ummjiil ^hb rcqiiirod for 
a loAJc Uubi^. It wAh dlfc<r fouuO Uiat by heating 
to 90" or HW* 0, it bocumc much more difficult 
to CBVee inloxiralinL in i^enidtlxcd snimaU ihflQ 
to BtfUtiJtii'/T tli^ni. Uraredku coitdudccl frtjiii ihtm: 
OKperiDiGTitfl thflt sc-tisitizin^ end taxic eLlelanGQa 
were diAtizn^t froiu *a<rh oilivr, Voughjin nnA 
Wheeler by diirefititin ^ith hoi abbolute akohul anij 
nuditin fiviirdtc ohinincd ji pcpAmtion of olbnmin 
into tvro parts, ooc of i^'hich ^iiowM o marked 
sen^ituin^ proiwrl^ ard bnt litlle toxicity (flI[.-i^j)iol 
inwhblc portion); the ollict pcrtior (nicohol 
aolublo)^ a more tiigtily toxic action, Ther coc- 
r]u<1cr1 thiit iorK iir>d m^niiifiiFing Mibf^tflnE-pA wrir 
pruscut in the aaiue niolciulc uut} tlmt by ihelr 
pTocosc a fplittin^ of tJjc mobcrok into toxic and 
utriitilizing ^runp»i wu* ol>Uiinf''l- 

TliL- wurk tit Wiiiig,\mxi nnd Whi-eler wiisi doiu- 
00 vltolo e^ while and oUici" crude pTOteui& 

Wolle, ^rorkini^ with pure cr^^Uiz^ filhumi&» 
ohdincd toiio ttnti t^iMiUzin^ nHion in thi« vr^y 
in quantities euiaUer tlian tho^e n^preeected hjr 
Vaughon^a iLinimiim tcnvitixinK ond toxic vpiit 
pToducU, It lecma poaaible, thcrefor«, that by th* 
proceM of Vaughaii end Wheeler aihoudIh of pro- 
tein too amall to produce toxic effects, but capable 
of tenaitixiuj*, eAoapvd uplitting throuj^b alcohol 
prodpitfldoo vhile the alcohol soluble portion oon* 
liatad of toxic i<plil products. The action of heat 
may be due to the fact that botii toxic and «cnai- 
ttsiog auhflnncei are equally iniueneed, hut that 
the flp|>arent ciTrct Ji grenler oi toxicity hecauae 

lyrecfiox asd tMMUjrnr. 

for intoxkttioii iiigtr UDiMiitB ere necM«r 
for KontiutioD. 

Wcllf hu alflo «hovi diat tonidtr and 
TiuBg f>ropcrtti«i d(«Tc«M equally by tryptk ^gm- 
>lion, and that bnlli divitppear with the dkappcsr^ 
a«« of beat toaguUUe protoifia. Aecatdiag io 
V^i, the tmpotlaiKv of ike action of lM«t fe ^ 
to th« eoagulalMiB of proU-id, tboa nnderinfl: It 
Capable oF beidf Uk^ ap and digaatcd bj Uie 
Imooc^M, Caaetn and other protciu which do 
Do4 raatgnlala tm boiling siilTpr no rhangv Ikratt^ 
beat until a texnprtntutr vhich dcatnmi the pro* 
bin volecmle li reached. 

That toiic and *eftntiiing aubOanoca maj ba 
doietjr rtlstfld to t}m nramatic gronpa nf tlv pro- 
tein mol«ciile U aofxcstad b^ the fact that seUtu) 
vbich i« dorad of trrceiD and coctains littii of 
other ammatii* groapa doc> not prodniee the phe- 
oomena of anaphirlaxu (Walk). 

By the injfction of serum of acfuitmd animnla 
it b poaaible to pmdiu* a paaaive aeiuitinllaD, 
analofow Io pasette inawanitj, and in iWm vaj 
to demoutrate tbe picaencc of aa aoaphviactk 
antibody. Thii antibody bai retf«k«d the Dane of 
'^naphTtaetin" (Boccnan and AndCTCon), or 'al- 
lerpn" (Andenon and Froat). It b pooaible to 
piDdnee paanrr anapfajUxia in raHona aniaula, 
but* aa hi activo anapbylaxifl, tbe gninea-fii^ ia 
fae>t ttUpIrd to Uk purpoae, Traneniiauoii of 
naaphylaxij From one apec*c» to another b a^ 
posRblo, From rabbit to giiinca*pig nnaph} laiu 
IK rradih tmnvmitted. 

The neccjuiry interml of time elapatng behrccn 
Cbo injKtktt of the ann eomtainin^ anapbjiaetic 



antilxHij an<] the actual Kn^itimtioii of the animal 
TATic0 vith t^LO dilTer«nl ni^t^o^i of injectioa In 
case cf inlrBprrritoRc^al injcfUoii tJiin time ia about 
twenty-four hours; ic ir^tiovcno'is iDJG>ctioDS it v 
about ono ftcd oae-half lioore. 

DilTL-mit moniis of mcudumg tbe eeDfiituing 
atf^ptli of aiitj<icn3rus bftrc born inggertcd. Doerr 
ADd^ Rut* iBJ«olod ^fcrCBsing quflnliti«a of tb« 
itrnnn into j^n'inm-ins^^ mul Ihrai b> iuj4<cliiig 
tvcnt>-<four liotii^ Ut«r Atk intoiicntiBg qa&niitr 
of aiit3E*n Jnto *ach of Ihwe pi^, tJ>e nmrnint of 
antitfmm nncoMarr to produce soHwti/JitioTj vai 
found. A wcand method U to injort a definite 
<|UflntilT of Anl]>cn]in into each of a feriefl of paga 
and lhk>n tnt^nti^foor hour* Inter to in|«c1 docrew- 
in^ quanttliiv at tmiigt^ii Ut ^wl lltt mualleet 
amount nfccMarj to <AUse acute- dc&th. Doorr 
and Ru^fl i^i^ifp^t AN n unit nf nnaj>hjlnxU onti- 
»crum r>r of nunplivlaotin tfiich a ftfrum oa vill In 
a doee of I ex. intraperitoneal 1^ aauitiw a 2^ 
pn. ^IBCA pijE fo that ncutc death may be pro- 
duced in twi>nt_V'foiir houn by iDJ^ellnj^ a eufBcknt 
quantity o( unligeiL. 

Tbe close connection bctvcen anaphylact<^n n*iaii*a « 
and prtcipitinogcn has already been alluded to. ABti»*ai««a^ 
In a timtlar vay. aniphjlactin and pr^lpitEn are 
ao vfoeeh allied tliat Pri^berger, Dnerr, and 
•there congidfiT them identical. A« objcctiona to 
thia view it it pointed out llmt animaU vrbich do 
not readily produce prwIpltinA* cnrh ee gnlnea- 
pi^ and ilo^ are moat anoceptible to «eQ»itixation ; 
and KCondJy, that in the itatc of antianaphylana, 
1o b« deacribed later, pre<lpUiBi may be pretentj 
bot apparently the anapbyleftin is exbauated- 



Co m p l« lu* n I 

IB AflM> 


Thp ariBphylactio antibody h tb^rmofltabilo ti 
Art ^redpitmi Aud agglutininn. TliAt is, It rcusU 
ft t<imi>crfliurc of Sfl" C- for one-lmlf hour, 

Mirhiolifl And FlffiMclTmniiii oUin^v^l that dur- 
iii^' mill after ftiiaphvlacUc shock the wrum of tJw 
auiniul b(!fjiiiir poor in complcnicDt, Sleoj&wijtc 
found (hat fr^llowing tho Moond ftntigcn tnj^JDnf 
couipJc-iiB^jl Ik^^u Io dianppoar After fltc raiauteA, 
And this (lipafppnroncc bcconc fnnrkcd in thirty 
minutes. In caioa in which death took plai?« 
quifklv orij complement (^impppftrAnce wo* not 
\'ct Snr udiniicciX u fiirtlicr di*upp(?iirAnt'i; could be 
found hy nlbwir^ Die £«nini to i;tand for a vhile 
lit tlir tr.^t IiiIh' 

ThAt the di»Jippcaranrc of cortiplcincat i« in 
itsplf not T&fponfiiblo for the a fiaphy Indies shock 
IK xliuwu ill t»ci vny^i fii'sl, Ifie iTijei'l Irjii of ['[im- 
plcmcat before or after the eocord nntigcn injoc- 
tion do(^A not present ahock. nnd i»o(<ondly in mott 
lapidlj fntal riiook^ death take* plat^ Ijofore eoni- 
pleiiient Im^ Oisapi't-aieil to aiiv extent. Fiii-dber- 
ger And Hartoch iiavc aUo shown that injrji'tion of 
GO mpl cm en t -binding fiilt lohtti'^ii inhibit* ani- 
phylaHiP wymjilonH, vlren il in injoi'ted U'fore the 
»e<:t)iid injection of fintlgcc (acc Cliapt^^ on Ci^iii- 
pkjnicnt Deviation), 

111 order Ic fttu<ly further the relsHon of eom- 
^'lerient !■> aDaphylairiB. Frinleniann K^sitits^l 
rflbbita to oi-b)ood corpn^cfcf and thon added 
tnactirntcd Rcrum fmn thpsp rnbhitu to an crrthro- 
cyt£9, in t)io te9l-ti?be. He foiind that whan com- 
plenient uas adJoii to Jiueh a mixture, it Wcame 
toxic And cnpohlc of protlucing nnflphylActic (ymp- 
tom«. By prev&nlittff compitmt-in binding, bv 

fUBonim OF AyjLPBrLA.iw. 


complcmcnloid, cic, the formntioD of toxin was 
preTenied. FHe[lbf*r^*er whu «hle in « simiUr wnj 
to produce snUitanocfl wliich csuFcd symptoms of 
anAphjIfl^iB, by trcialm^ pL'ceJ|)it]tiogon£ Uom 
varicm* Hourcnji wiJli pitviprtinx in the prftRpnrp 
of cojiipIcTncct. He tbcrtfore auppoaes tluit tli» 
toxic RUl»tuii<:o. which lic callit nnjiphylnloicin, is 
deriW from ibe j>rLfipilttte eaui+ed by prtcjpitin 
acting on prteipitiuojf^ii. and tliiit it if^ tho sp^ciJic 
MUM of iiit<*XJratton in flrAphylaKJf. Aa there 
pjtinU a iliJTc^r(*ncr (»f npmiiui hh in Hit* i^t^ntity of 
nnapli viae till, ao tlteti' uxl^l various tljeoiics as to 
the formation of nnapbylatoxin, 

Bichct 9iipp*>ftfld that flniipliyTncti^ antibody and 
imtiftrn combinN! to farm t}ir poisiiiou.* subslHncp 
Tvhicli he called "Mpotoxin/' Wolff- Eifner, Weich- 
hardt, Friodciourn nn<l oUioi^ coEifliJcr nnaphyl- 
actifi to lie of t\w uatun? of n 3jtic ambocuptor^ 
■ad tliat, bv liu^ tvction of complement through 
tide amboceptor, n iqiiiUing of aaaphy lactogen 
into toxic KabffUncni takc« place. Vaughan and 
WbeHer. witli otliei'8^ L-ont'iiier that in F^nailiEa- 
tion we h^w to do with the di^vclopmont of spe- 
cific protoolylic formonU winch *plit t^c nnti|?*^n 
into toilc groups similar in natuie to their toxic 
products oLldiiied br liydrolyas with ulcobol anil 
«odiain hydrate. This view i.i iupportcd by the 
fact that Biedl and Kraus have pnxluired lyrup- 
toms of anaphylaxis hy injection of split produotd 
of protein (Wittc's pcpiom*) in do^ Th^ pro- 
duction of )&fn;a»cd protein aplittrnj: power of the 
flemm aft<^r inJFctf^n of forergn prcteina as 
domonjKtrnted by AhdrrhiiMrr aUo mjpport* the 
mapnc theory. Accerdinjr lo thwc vicirs, rariotift 


tspKvTiQJi Asn rwHPv/n- 

sinApKjlntoxtiiK arc nf vniniljir ctharju'tcr but 
fonc^d tJiroitgh thv action of eubeUno^ whicli 
arft of specific unluro, 

TTwT siymjiti-itTiH iif aimpli>'Uxiii Tary wilh differ- 
ent Qnitiialfi. It i« ia the ^nuaco-pi^ that movt 
ooQfttanl results are obtained. Sjmptoms begin 
jit dilTcrent intj^rvnlfi of timrr, nftcr the woond 
injection, with different proteins. With animal 
protcini, they appcur in about fiftucn minut^N 
aft«r iDtvupertloiienl injueliun. The u^uiplonia 
usually appear eomcwbat later vith Tcgctablc pro- 
teins. TliQ ontmal bci-^mcfl rctlcju, there is i 
tendency' to aoralofi. tfic linir fLlnnds on t^nd, ami 
dilBcultj in breathing comes on. Paralyeifl of the 
fiind ti^ if comnion nith unimAl protcina but ia 
less common in plant proteins. The respiration 
becomes spji^otwlic^ the flrimal i? unaJ^tv U\ *tand, 
convuleiiTc n^oTCTiEcnttf occtir, and death follcwv 
npidly whea n fatal do»o is given. When a &on- 
1«tba1 dose is givpii syinplnmH rnny b<? dt'layed for 
an hour» Death commonly occur* in fntdl cnsr* 
insider of ftQ hour and often in kai^ Uisn ball an 
hour. In iittrsv^noiis and intracardiac inJ^Hom, 
the eyinptcms follow mnch more rBpidty than in 
intrapcntoniral iiLJectjon^. In nubcutancoTU injec' 
tiona, the a>'mptoms ooonr long afUr injection and 
nrp inrnnatflnt and mnrh In** wveri* than with 
otfirr miy;« of nUorptif^n, Fafnl rufnulbi jirc iimdi 
more dilHcult. to produce in eubcutaneoua injec- 

Th^ blood prpsmre i* raiKed and lowering dwH 
not take place until shortly before dentils A Ttry 
importitit symptom is that dBftcnbed by PfoiiTe:', 
who observed a conntflnt etidden drop in t«nip«rn* 



lurt, Tliw HyiTtjiluni in coiii^Jdnrt^ of great ding- 
noatic vaJue wheo the dc<»p aiiiouota to 8* or ^^ C- 
iLnd othor oxpcrimvntal c^^iid^iOTie are constant. 

Id dogoj th* Rvmpfoins Tarv greedy from thow 
in g^in(?[i'pi^, Here a chnra^r Ecliptic fn)1 in blood 
proseiiro U fmin^. Vomiting, involuTitAiy urinu- 
tion HJiO (J^fecfltion, pflral>iU end univosis me 
comiDon irmptoms. 

Thu re*pJrclorj- mccliuniMTi or ahwk in gtiinca 
pi^, Bccordtnf to Aiior and Lewti. ia fhtt of a 
spumodic contraction of the unstripe^] nuwrlc of 
1ji« bronchioles refulting iit obstructicn of iha 
luitiL-n, ncuti? iMnplivKcirtA and j\9Aih from nuphyxi- 

Section of the vagi doe^ not infloence thi* pttl- 
iD0sai7 ph^DomeDft. indi(?ating that tho eiToct U 
a p^riphvral oni<. Si^IiuUk fiJi« vhouu Uuil thc^ 
unatrip«d iriuac^ti fiber of a feaiitii^ ^inea-pig; 
contractc moro vijofonaly when spocific soriirn id 
applied diret^tly to it than M-ben otlier soruui ia 
uwdn Atm|;ifi, tt'Hi'h utta -m Uie aorvi? euJint^. 
cauws an inhibition nf niaptoma. Mnrked i^on- 
f^tioD of ihti nbdomtual lluod vcg&gU is a com- 
nion fitdinf^ nt aijtrjjisv. Vaiioua hj^pno(ic nitcT 
narcotic dni^v hare bcrn dcvcribed ta inhibiting 
anaphv lactic Avrnptome, hut tlio affvct seem a 
msinlj dne lo n maAking of sjTnptome. 

A licii^itixm) animal which hn* recovered frnra a 
noQ-lel);al toxic done of protein li refractory to 
th« action of a later doeo. The condition of ench 
an animMl U knnirii bm antirniAphylRTiia^ And it 
ba« \tt^en deniontUmtcd by failure to produce pa»- 
£ivc finaphylaria by using tho acrum of an animal 
in a t£tAt<* of antiflnftphytaiU, that th« condition 



llfirECTitt}/ l\/> IWWfJVJTT, 

]« Aue til an rxliflii^liou of aDnphyladii* nntibor]}-. 
In onimaU whicb lmt« boen actiroly eonntisod, 
ifn> prrioi^ U H tmiiiirnt otu^ fflllmriv! hv a rPtnm 
of h^>fji'n4iiHvptjbtliU iliw. to (^cuiliritJt'iJ jit'ULliictiau 
of antibMbcf. lii pn^uivnly PCDMtiKt^d oDimairi, ii4 

depends on tito anioimL of nntij^im iuj«irt4.*d. If, 
for idntnnro, Uio nnimnl K in^fBci^ntiv pcneitivo 
to hIIoiv of (l^fltli TroMi u large toxii: ilose. L}if* anll- 
gen rcmaiDin^irUl |iroHuc« aci active »ni«Ttij:atica). 
If the snti^^OQ lit jtidt tuoui-li to iiculratizc the 
atiflphylactin. the snimnl vill tb^n be. ha before, 
wnf>lih^ih If the ^ccfinJ t^ose is (no ^mall lo 
neutralise the unaphji Inctiu, tbnt wiiiali TcmniDH 
will be cflpabl© of pi^ncmg further reAction^ In 
nniriiitLH imiiiiiiii/inl lo profi'Tnn nrul whirb hiivr « 
high concentration of aiitibcnlipi in thr bkiod, vo 
thiU pniviivo annpbylascLe may be transmitted to a 
Meoiiil nnimal by thn viRf^ of fl F^mnlT ijuonlity of 
ecraui of the iinHiunc unirtinL it strtlt- of jiiilitiriw- 
phjloxia may be proilucod by tnjectione of amounts 
of fifitigi^n tcio vronll to prodiicd n Tatal retnlt. 
Fn (bi* <'a*e, v-'e !mvu a« nrLimal wbteh \h luitinna- 
phyJactii^ aUIiougli poue»«LD£ a Aeriim cootajaing 
a hijfh of>rfcii« ration of nnapbyloctin. Kncdbcrgor 
Buppoaea that in Ibli ojue tbv rceepton of the oella 
are occupieJ l;^ fiUMpIiylactu- iiuliboily which is 
not icarbetl by the injcctc*T antigen, thi* being 
neiitrnlSzed by tbi^ rirculfiting annphykctioH 
Tnt«rfliinii T)it* rt-lutiou of the luUn-culin reactioo to ana* 
4>*^mmri pIijIaAis (see Tiileiiulonin) hne been thp si^bjwl 
of much dipCH^on- 

Yamanouebi cucccodcd in producing anapbyl- 
aetSe nymptoinM in gninea-piffs hy sen^Hiaring thara 

ji/;nrv djshabk. 


with wrnim from lukrciilfjiis putienU nmi thtfu, 
twpnfV'foiir hour* I«lnr, injorttng tiilicrcnlin or 
tirberrk haciUuft emulsion. Tiail pnaMvdj EWQflJ- 
tizod jzuinrn pi;^f hv the injection of tiibcTriilouft 
tiscue4 anil in this wa_v obtniDed nngphylaetie 
»ympt<ii[ift hy injVvtiu;; liiWrcHliu nflni' tw<^ntj- 
four hours. Hotmholtz |>roduced pa^eivc bcoeiti- 
zation ii^nirikl eiilniiyous; riMtttion bv the injMum 
of KHJin fioiii tuberi-ylou* uiuinea-fji^r? iiilo tlor- 
innJ ^'(1 i 111" u pipy ^o Ihut nfu-r twon1>-friur liuurs, 
Ihfn,- gnvu H imsiiive v, I'irqiiet tvsi. 

Jn coQti«fit to Ih*' te.-iiks of Yainanouchi and 
Btil, utbi^r inrestigjitore hovf giic^cdod in pjiciiiTo 
wuMtiffltion of giiinflfl'piga hy injection of aeruna 
from tuherculoiia animnl? dthor only ocea ■ion ally 
or rot At alL Production of onaplijrlasis by uiMivQ 
miftili/iitmn with Inbcrculir i* pflficiMn only aftpr 
repcotcJ Inreo dopp*> ft would Hoein, tlierefore. 
tbnt as in tlK- oasL' of othor bacterid, tvphmrl, <\yt- 
vfntf'rv, vUv^ Ibr nniijibylaiit ih nj^ninvt tho |irntpin* 
of the lubcrcfo bacilliia rather than tli'' toxin pro- 
flvcod hy Jt- 

Tht iiiiti^wnri] f'Vniptonis follnwing the injec- 
tion of curative toruiiiB lios boon Lho eubji^ct of 
atudy by miny fnvettigalor*, parCiculntly v, Pir- 
c]uct nut] Schick, ItoAcnnci and ArtilcrEon, and 

TIu! Tf-Action fo1tf>n'tng a primary injection of 
4crum Appeal* uflcf a period of lime varying fiom 
a few mioiitL^ to *e\^ral wockf. There may be 
*\\lthi rfdiii»*ui flnd iffhinp nt the inoriilatlon site. 
and jMellin;; of tbt adjuft-nt lymph plntids. TUtt 
promifient *v-mpljmj» niv fevvr, ikin eriiptionAi 
f^dmna ami Joint pains, Slight altfiiminiirin and 
tenkoperrn hare been neiterl. 


f\rEV7iOh- AWa IMUO/fiTT. 

Thit TMrtion vanc» m w^wniy viHh ttie amount 
of nruin tised but mdividutl variatioo OLE^d differ- 
eD<va tn ihip wrum ire the mfwt tmportiint faetore. 
Tho reaction following a fi«coiid lojecLiou v. Pir- 
^not and Schtd: dirido into (a) immofHatc, 
appnftHn^ ^ftpf m fwr honrii, or (b) delayed, 
Appcftriuf; after a itw da>'a or a week. The »,vinp* 
torn* ftre similar to thow (oHowio^ a primary 
injocLion but are ruonp likelv to he tnwrss and raajr 
be Aixx>mpfiD>«d by vDiuUlti^, cuuvuli^iuuA, collapm 
nnd, rarclj, d«ath, 

Iho abnonnal nfletions fol louring a »coad 
itijftlioii aiv mere liket;v lo Apji^ar wb#n (lie 
patient bs» bad a reaction After the primarj injec- 
tion; 0eooDdl>, wben lar>:c amounts vt ecruin hart 
Wii girm in the primarr injection; and thtrclly, 
\ritli A history nf arthmn (c^|>^cia!lv in anthmn in 
irtiicb the attacks ard brouglit on by pro:iimity to 
bonoia) or hn\ f^wr» 

It has bff*a tugg^U-d thnt, in caM« riK'iwKitaUng 
Mcoiid iiijodions of nalitc^in, & ^mall amount, 
J c.i\ or )c»«, bo guea ai a teat doee to be followed 
by 1h« nervAiarr therfi|M^iitic' i\tv!0 twenty-four 
honvs later. 

It i» iniportant to be «ttre Uiat tlic antitoxin ia 
not iiiji>ct«(] iDto the vein b«^ftu«e of Iho fact that 
anapb^'lndir K^mptotiiA nv" [irndiiii'd jla mutli 
mom rc^adily by itilrnveitous iujeitioaa. Thi^ can 
be avoided br preliuiintiry flapjration junt before 
injection to 6*^i Dial blood doun not outer t)ie 

RoK-Tinu rtnd Anderson have dcmoit^trntcd the 
preBenco of onaphylactin in the blood of mcu who 
h«T« bven inj«ctrd with nntitoite hor«« verum. 



It has b^en suggested that by passive sensitiza- 
tion of guinea-pigs vith patient's serum^ we can 
flscertain whether or not there is any danger in 
Becoad injectiooB of aeniiD- 

It has also been suggested that a cutaneous teat, 
similar to a v. Pirquet tubewulin test, be made 
with horse serum to find out whether or not hjper- 
aueceptibiliCy to horae serum be present. 



Allhou^ a coiuittent claeeiflcation of the lofo 
dous diECAaeap on Uie bajtit of iotmuuitj, b iinpov 
libJe at the prcscait tinut, a certain gjoQpmic i« <1^ 

ftiralJw fur tin- sake of i'unveu]ai(.->e. Tlit foUowing 
arrimgcmcFit of tho^ ihecascF ^^~c ore ivblu to coa- 
Bider is made on a baeis vhicb is ptrtly «tiologic, 
partly ^itli nefereiicff to the patUoge&ic prcpertitt 
of Uie micro-orguuLfiiue, oxid puriljr to tlie uaturd 
of the reycfioria e.xcitol tu Ihr liocljr by infivlion or 
uniDuniifltion. In some iDfltflDCCfl notbing mora 
thaij general snaEogiM suggest 11ienifie1vt?g fli a 
baals fur liic grcu;t[jigt whidi is nccesanhlj proti* 
eional and impcrfiKit 

DLBC^fises, nulunil or u\f>:-n menial, wliieh are 
caused by aoluMe loving of bacttnal, animal or 
pEnnt origin. hifL-cticm or immiinJ;^iitioji iii<tucea 
iiomuoity to aubflcqnciil Bttnck^ (except in hoy fo- 
tot), the immunity being cbaraetenaoJ by tbo 
formftlioD of w?rum antitoxbii, antJ occiL^iL^nAlly of 
bflt^k'noiyaiuft iinU ogi*hi!min». The ecmms of 
highly imtniiniW unimiilit an' prrHivtivi- aiiiil cur- 
ative for the correaponding mtcxicationj in mra 
unJ other nnimaU, 

I. DiriiTimnu. 

BaciliuJt diphiftcriie. or ihc l\lcbfl-Loct!lcr bncil- 
litSj va* ilifipoverpt) by Kloha in 1833, and more 

DirtiTffKtaA B.WlLLVa. 


fully described by LoctUcr in 1834. It aaswcre &U 
Koch's Ja^s ill iU rdationtliip to the iliMJihi? of 
diphtljcrtu- It i^ n noTJ-motjUv roil-ahnpc^d orgfitj- 
iam having about tL« length cf the tubercle baciU 
[iis, but twine it* tliickness- One eitd coinmodly 
presents a tlnsk-liku CQlargcmcnt. It stoins by 
tlrATu^e molhoJ, vith tfio otditiury umlin <]\v«. anil 
wiLIl tfie Gpecinl siaiii oF Nei&aer «hov^ a ptroalinr 
sranuletion, the granitlea of Babes-limst. Jt i« 
readily cultivated, especially on aolid no^dia which 
contain ^erum and in various boaillon^. It tenda 
to grow 111 (>o]ier{^nt miiBflcs ujt\\ under the micro- 
acopd tlie cclU often show n cliaroctori^ttc plialani- 
Uk« arrfingeincul. 

The <li[}htherjtt bacillus is iin obligate paraKitc 
hanng no regctativc cxiatcnci? outAidc of the body, 
is Tory roeifltnot to deGiiicaEion nml may romaia 
virulent in a dried state for from oae to fivr 
cnonths. Ita life m wat^r varic* Ironi a foiv Jayfl 
to several wcgIce, having ita ehortcat existence in 
Jistillcd water and ita longest in hydrant water 
i^'hiclj has Irocu boiled. It diaappeara more quickly 
from unboiled hydrant water. U la very siiaoepti- 
\i\c to ordmriry anttscpticj, bein|; ktll&l in a few 
minutea by corr^Aive ftiLblimnt^ «vtfn in a dihitton 
of 1 to lO.OOa 

'i'hc Aourcc« of Lnfcclion mcy be cnumcratt^cl aa 
follows; 1. From the false membrauos, sputum 
or excretioua of tlie moutli, pharynx, uom^^ con* 
junctiva and do«j>ur nwpirutory p£L»^g«« of )n< 
fpTted itidiTiflunls. S. From eouvflleacenta and 
those who have fully recovered, even after at-nun 
trcatmeDt. VLrutent orpmisma may piTvirt in tho 
pharynx or nows of cDnvalfflccnta for weeks and 
monibs, as in one of Prip'a caaea in whieh Uiey 


txrscTioyi Ajen ihmvnity. 


v"r« TouDtl twenty-two montl^e *(ter rccovory. 8. 
>'roui Uk upper nir pBCU|^ of htaithy per«oiu 
who may iwvrr iia\* KsJ flipbtlierijij b«t who hftxo 
been in direct or indirect conuct with the (Ua- 
ea^. Kobop obtftin&d virulent badilU from 8 p« 
ccDt. of the iiifliridiinis who hod bcos in direct 
coDlAct with paticnltt and ho stnt<fi that €,S3 per 
codL of xh^ people at larg* carry wjllk them viru- 
IcDt OTganum*. Thi« condition itiaj wall occoxiiit 
for the ***ponUncotw" origin cf diphthi?rifl in the 
muoi^tihk. A. From aiten uf latent diplithena a« 
ropreoratcd bj Tronic pbonni^ca] dipTithcria and 
cJinniic rhinitit fit^nnMO, 

HctiCT, ttifcclion Inirc pUt^cr chiiiHy b^ (Iir«et 
eoDtact, but frequently alio by indirect contact. 
TransTnisslaD by kissing or by other mefloa of inti- 
mate contact* by wt\f infected cupK or toja^ ia 
woU iftuo^ifod, "Droplet infodion/' i. «., from 
Infected globule* of inutus or saliva whifh the pa- 
titnt emita when ^penking or coughing, may oeear^ 
but porh&pa ia not of gr^t fiiguiflcjuictf, Thp came 
probably i* trtiif of •'ilust iiifeeU'>u/' althoughp ft> 
vtatod. the cr^anifin may rciniiin hnuj^ ant] nni* 
Iftnt in a dried state for a long time, Th« disense 
ia rarely traiiniuitttHi from animab lo man, al- 
though auch trariGimiamon may occur from Ihc cat, 
whicb ownmonnlly aufTrr* from Irm? dipJicheria. 
Tbe dipiithcria of fowls ia due to another organ- 

Tliu upper Jiir pnKinycc, more rcrrly the ranjunc* 
tivn, wonnd5 mini the vulva, arc recognised as in- 
f Action ctrtu, 

The local and genera! phenomena of diphtheria 
are caused by the Aoluble toxin whicli the orgftn- 
ism secretes. Although Ihe foxfn ifl not abiorbpd 




throuirh. nor doea it injure the nnbroken skin, it 
prodticoa nooroaja of the rrni*?ou3 a'lrfacee aod un- 
(Itrlying tiHAiic at the siTe of lEjfeclioi^. TJimugh 
the woiindeJ surface fibrin-forming eleinciib 08- 
cape, 01 a coQ&cquencG of whic^h eucceeaive layort 
of fibrin are ilepostUtl aod l]>e fibrin,^^r witli 
the necrotic Bnrfaw, louc<>eytes an' J as^OL-iatod 
mi^^ro-or^aniKiriB eonslitute tlie membrane which 
to often marks the disease cliQicaUy. The locsl 
pToo««A i« similar in diplitLcria ot cutaneona 
vrouiidH. Tlie toiin h<womes gerienili^wl by aliHorp- 
Lioix thn>u;;h the lymphatic ctrruintion, 

Chwrarlr'riBticiiliy ihe bftpilli are oonfln«d to the 
Bile of infoctifHi. Although diphtheritic haclerie- "' *** ""''■ 
mia rarely ooeura, the bflcilli hove b«m Found oc- 
rjwiDDEiliy in Ihe hload rind viaceni of fatal cnheR. 

The clinical and anatomic conditicns lead U6 t*j 
believe that the paronchiTnutou* organs, the iym* 
phatic? tiMiue» and the cells of the ncnous ayBfem 
contain rtjceptora with vhich t]ie toKin unitca, in- 
afimtioh an thotL' tisanes euiTer dt^nionsfrahle injury 
during ihc disctwc- When the toxin jh injected 
aubeutoncously into anima]*, locftlistcfl cd^rina and 
neertwift occur; hence, the connec^tive tieents may 
aluo lake up ■ portion of the toxin, diverting it, 80 
to say, from tlm more vital orgutxt. 

Mixr?(] infrt^tiiiiis rRiuU-r iliphllit^riu a mortt Jan- 
gnrona di^cnjw. According to EJaumzort^n, U^c 
fltreptococcne lA angociat^d n-ith tho diphtheria ha- 
cHluB in ino^t casea of diphtlieria. The obaeTYa- 
lion of Hqux anil Vorcin that Ihn ntrc ptococcun in- 
rreniieH th? vinilrrcp nf the iliphthrria bncilliw 
both in the lost-tube and in animal cxporiniMila 
nuy explain to some ^o^r^ th9 eeverJty of tho db- 
ffiM when ac^ompanicKl tjy alrcpt4Koocus infection. 

Mi ltd 

ixfi^vriox AXD iitMV.ytTY. 


AnU\fi frdtn i\v* lornl innuoiuw nf the struplacoccuv, 
however, & general ioTaMOn by this or^viiam maj 
occur, with inch coiuequoncoft ae iicut« nepliritia 
or lobular pneumonift, and in thia coDdition the 
di|J]tlL«ntic infection maj fall into the back- 
groutiil in imporUnce (c«pt)0 diplitheris). PoAt- 
dipljt)L«nt[c fiuppuratloDs cDiunioitly are caused bjr 
the pyogenic cooci, but oornctixncs in aaaocitttion 
vrith tho diphth^TJa budtluft iUelf. Rarely tli< 
baciLlus is found iu puiv cukurc iu lobidar pn«u- 
umniJh* a coudiUon whic^lt riexxwr and Aiidcrfloii 
ptii[liici?d iixpf^riint^iiUlly in uunuiIsL In puri^ 
perol tnfcclion« with tbc atrcptococcus a, puerperal 
diplilheiia la somclirne^ inperiiupoMiJ. 

Vt-ry jounj^' i>}»ildrvn nwist diplithmtitr infct> 
tiou- A ccrtftin degree oi immvaaiiy may be traa^^ 
milted by the motlLer^ ObscrvatioQii on animals 
[diuvr that wbcni Uic bTuod diid milk of Ihu mother 
contain antitoxin, the olF«pnDg ac:quirca aotno pro- 
tectioii, which, however, may diaap^iear afti^r llie 
oenation of nunijig. Polano cburua timt anti- 
toxin piiAAC^ from tlic mot>iOT ia the cbUd throu^ 
tJie plai^eikta. From the wcond to the screnlh or 
eiKhth year children uaually aro very euficcptiblo. 
Thin itiHt'cplrliilily 1% not uniforiH, however, for 
many children c«copc infection, whereas others 
tjnd«r tho «amo coDiliUona, contract the diseuo. 
FulWing Lhhi period Auaeeplibility decreases and 
after the fiftei^uth ycur the diseaae b rdalirdy 

Thu caune of Lhit immunity which devclopn in 
the abecDcc of a prcccdinic infection hoa not been 
AuQEciently invesligatiHr In some cases coneid- 
crnMc umounb of antitoxin are found in tiie 
aerum, porlmpe enmi^h to Account for the imniun- 

/jfiffijvni' /\ orrifraSiaA, 


ity- 'J'liC prolonged presence of bacilli of lo\r 
Tinilenoe in tlio noeo or piiarynx, or mild attaok< 
of tike dieeAW wMch huvi? not ha^i) r&edf^ix&f], 
n»ay caufc U»i^ ili'Vi'lapmu)! nf dcitituxin, A« 
Ht\M in an f^nrliev DhHptr>r, tho ^o*» of Kiiitiiltlc 
rfrcptors mftv ht &. factor in this tv^n* of arifturoil 

Hypertrophic toneilB and chronic pliaryrpUa 
appear to be pT-cdiEpo&ing causes m cbiMrcu. 

SjioiifflHEong recovery (8cti7e immmity) ie due 
to tlie formation of (he specific aiititojio hy 
tlie tiseuea of Ihr pnttiTit. \Vr mny rci^nnl the 
relationship of the leucocytes to diphllieritie in- 
fection ns Hot ilcflnitely *i"tt!('il, AlLfiHU^li Icnro- 
c^'toais is a fairly coiuttanb occurrence and mAy go 
Afl hij*h as ifS^OOO to 3O.UO0 to the cabtc milli- 
meier. it is dilficnlt to diraocJate that dtie to the 
diphtbcrilir iufiH^tion from that cftuwd by n mixed 
infection with tlic stTcptococcua. Both polvnu- 
clsar? .ind mononucU^ra nrQ incr«i]«(?d, Uic Intt^^r 
Iwinf; (specially inarkt-d in tliilJreii (Kwing). 
The opsonin content of tlio eeruni in dip}ithcvm is 
boJow normal nt thp onfct of thf disrnse, Ab tlic 
t^rnptorEiA Hiilmidi.' HTt>1 llii' inrmhntTii^ iliijipjHriir^ 
the opsonic indi^.v nset (uu»idershl>, rctLuning eu 
normal in from two to nino days. 

Injection of doEid dipbthoria bacilli in 6iiitah!« 
narnheis Into rabbits is foIJowet! by a rise in llie 
opfonic index. Irjcction of dciid dipbtbcrin bacilli 
mny provi' or *L'rvice in ridOinji :b& thi'oale of 
baci11it<-cflrrii?r« of bacilli (TunnJclllT). 

HeLtfiit fX[ieiirr]L'[it>4 bave ^LiLsUiiLlaLvd t)ia ideaK 
of Deliring tliat bacterio)y«Jns are of little impof- 
tukoo in immunity in dipbthoria. 


r\F£OTiox A^D iXMtjyrrv, 

'Vht daration of ftctirc immunity to diphtheria 
vftripis ^rriifly, Uminllr un tndivtdiinJ liM diph- 
theria but once, yet not mfrcqucntly tlioee are tH" 
couiitorfti wlio suffer from reiioatecl attacks. In 
«ninr< ini(fmi^i<A i]\ti Hiisttcptibility cnntinuiw info 
fldiilt lifo, 

Pv»BhTiK«i«. The ndvcul of *0Tuthi'ru^y juBttSoft no rolaxa- 
Ui>n in the GiififoniRry prophylactic meMurm, aucb 
aa iaolation of tlie <li£OBecd« qu&r&nUne and diain* 
faction- A pntimt ahonUl not be consiiJered hatm- 
IdH until hb mouili, pharynx ami tiuxe are free 
from bacilli, a condition vhich nia^ hs brought 
about by a^^]K«pt]o applications, and for the do- 
tenninalioik of winch repeated bucrUrJoIop'c exam* 
inntinr;* arc ncccwary. Tl^e danger lliat others 
who have been in contact with the patii^nt may 
carry :he infection sboiild be mot hy appropriate 
IreHtmcnt. It Js not tn S)e forgoltpn that anti* 
toxin docs not doatroy the o^^5a^^lenl3, The injec- 
tion of antitoxin ia our moat ofFecfive m^maiiro for 
inilividuiLl pniphylaxii^H 

9«rMb*rKirj. Expt^rimcntAlly, it 15 pofiBihk to vaccinate 
ai^ainat diphth&na bj the inoculation of doad diph- 
tbena baeilli, or fritraets of agar cultnres (TJp- 
flleiu, al«o BaqlIl anil Gui^noni), but tfie couditiana 
hardly warrant the ust- of Uil& nicthini fur iim* 
tccting man. Estracta cf the organiama may be 
nailed with antitoxin and inj^tcd for protection. 
This U tht* *o^nIl<>d a'^mvll^'pinrtti^^^, 

Tlie elTierjcy of diphtheria antitoxin u *o well 
Jcnovn that little comment 1$ needed. It haa 
caused a rcduetfcn of moro than 60 per cent, in 
the mortulily of the disease; from 41 per ceuL to 
8 or per cent., according to Bagicaky, 

lilt'liTHKHlA AMTlOXiK, 


ifcT prophylaatifl irom 6t)0 to l.UUO unitt arc 
^"iierally rctvjnm^xulw], aithough some foreign 
authorities give only 35> uniU. Itardy, iodiirid- 
uaU wlio have received such Ireatment dovolop 
diplitheria wiLhin twenty-Jour houra after tiie in- 
jection. Id tlitse casoe it le probable liiat infcC' 
tioo has ftlrMiiy opcurr&l iind symploms «pprMir 
before llie antitoxin i* thorovgfiiy dialribiitcd- 
Nnluruliy one iHay coiilracl dipliLhena .iftor UiO 
antitDtit! ia nlimiitatn]. 

For curfltifC purposea Uie amount actually re- 
quired Jcptniiji on the virulence of the infection 
and the dt^rntioii of tho tVi^pnsQ. Inaantucli as th^ 
Ttrulencfr may not be known accurately, what t»P' 
ptt4n to be an ejrces» of antitoidn la alwaya de- 
Dtandcd. nnvin^ in mlrtd the averu^ doae of 
SJOOO luiitfl rooommrnded by tho recent edition of 
ihif lTri(*?d ,Stat<?fi Pliannampeia, tlie physician 
miut bo ^idt^d by tho c^onditions in the individ- 
ual eaad, L^es than 3,000 nnita are rai^ly indi- 
I'nUv}. «nd ;m rnuuv n* 10.000 nnd 1*1,000 iinitg 
may be s^r<u vitbovt detriment to the patient. 
ThPTe EhouM be no h«Hitation aboiit Tcpefltrn^ i 
do*e witljin Iwmly-four liour» in the ab»«-noe of 
distinct improTcmont 

Ransom and Knorr atute that if tho imtitoxin 
in (pTftn intravrnoii*!y, which may be done >Fitliout 
dftDgvr, the action of tho serum is about elf^ht 
hmin earlier than wbMt ji'iVtm iHibcutanHMwIy, Tn 
lOTcre and in Uic caflC« it i» adTiVublc to une this 
method of introduotion, the Bernm firat betnjp 
warmed lo thi? irinpi-rJitiiti' nf Un? limU, It xhoidd 
be rcmcmheKd, however that tho danger* of ana- 
phylactie sympton^^f are much iQCNa^ by intra- 
vcnou« injeetion. 


isrecTtos Asn iiiMcxiTt. 


It it prebabk tbftt ftw co«c8 ore bo EQitd or m> 
hopelcu, UD!tf«4 moribnnd. that ih% ooiunoD of 
aDtitoxic is jiutifiabk. 

The bvlicf tluit ontitoxiD fAvon the dtfretopmcnt 
nf fltphlhcritir jinrfllyHJB JR no longiT hHiJ, If 
(li€ic hae been en aclunl increase in tlic |>«TcaiUgfi 
of CdMi vrhloh sulTer from paratyiii^ a« «oin«tim€t 
stafecl, it is bccnUH- a Ur^ nuiDbrr of •erere 
<ttfi«0 H saved; aad tli9 »fcrc ca»es an thoM 
Ln which tbe paiit^nU mo^t fn>queDt1y develop 
parat^vi^H If nx accept the ricw of F-hrHcb that 
« apodal toxin o£ weak affinity for the anti- 
l(t\iii, i. I'., Hie toxon, c-a:up» (ho parahsEs, we And 
all the mopf jiiptificntion for inrgc dM« of 
SAtttOinn, for antitoxin ii'>utral iz€« 1h« toion ae 
wr^IT aa the luxin. Ort ttii* lihHJTi of expiTi- 
mcntttl werk Bonaom conclude: "Tmnifcrnnji 
tli« r««ult« (of experim^tB) to practice among 
human hdii^^t wc may expect ][l>fral iIoma of 
nntit^xin jcistn i^arh in th*^ ilincf^« to mtiiicnoc 
faTorably th» subsequ«Dt paraly^ie; and this fa- 
vornble inHucncc ia likely to manifeat itadf. not ao 
much in tho Iccul paralj's^ (soft palate^ ^tcOf fta 
in 6uch falal syrnplomg as fnilwri? of tlie hrart 
Sererc caeca, however, are likely to be followod by 
■omo uaralysis in spite of evoti lar^ dos^ of antU 

CaflOB in which tlicro is eevere mixed iofeotion, 
septic diphtl:*'riii, ri*i(j»f»ricl !fss favornbly to anti- 
toxic therapy than uncomplicated caflcs. At acme 
time s mixed serum therapy suited to tbti mixed 
iufecdon may \k yomhlt*. 

The suggGfltion mndc by Wossermcui of a com- 
bdmed treatment with bactericidal and antitoxic 
struma has not been Applied practically. 



rDaam\icI] its the senim of the pationt doos not 
ikicloij dg^luLmin&. 1-Le aggtutiDntiaD test is of 
CO valiic for the recognition of the disaise. If aai- 
mala are iTT"mur>i7Cfi witli tlie bacillus, flgglutinins 
ore siiitl lo be formeJ> The scmni of eucli an aai- 
maJ mn^ be used lor th€ id an ti ^cation of a culture 
matle from the throut, but this woulfl liJiTe no 
practical value, for tho dmgnosie may be eatab- 
liflhed by the ori^tnary bactenolo^c methods much 
more quickly and sAtjBfactorily. It U ditlicnit to 
obtaiu R homo^^oDcous nitspeiiBion of the bncillufi 
for the agglutination tc*t. 

Microflcopically and culturally the bacillurt of 
Jiphthmu cun be dijilin^Uhed with dilUculty 
from a variety of i^Uier ifr^^iibiufi which bcJ^iiig to 
the same ^rroup, oud \vhich are oallod paoudodiph- 
theria bm'illi. Thi' Uttor htv frHjUtMllj fouml in 
diphtheritic tbroate. but oecur oJao in the tipper 
air pnadagea and conjunctiva in the ahaonee of nil 
ItwiiniP, 0:i tbp wboJe, they are uou-phlliogeaic, 
but oeco^onuliy n culture in foLtoU whteh cauiHs a 
anbcDtsreoiia infUlralicir at the point or injrrticni 
in an experimental aniinah Hamilton cultivated 
one which wo* dutinetly virulein for uuimuk Their 
patliogenicity, lifiWi^vcr^ Ia Jilto^^^^hcr ililTfrr'iit 
from that of the diplitliena bacUlva inoamach afl 
diphtlicrin antitoxin doa« not protect ftf^iiut them 
nor do animala irhicb axe immunized witJi pasudo- 
dipht^ieria bacilli become immuno tr> the toxin of 
diphthprifl. Thr lianUitjt rnrofis. which in thouRht 
by MUiTie Ut he tlie caube of xeronin coiijuuctivv, 
b«l which ia alao found under normal coaditiona. 
is a pecrdodiphthcria baeillue. The nnimal cxp^ri- 
ment is the only po*itivf> meftnH of diffcrpntiating 
the true from tJif pscudoiltphtltcna bacilli. Some 






ccnsii^er them is diplitheria bacilli vliidi htfe lost 
tlieir virulcoce, 

Tiic proMOicc of thtsc orgiDisnit icaj complicoit 
th(T ilingnciMK ei ilipMTirria in mme gm», but 
there ie Httio danger of ^rioue errorn If onfi 
fouDd orgBDlflmfl re«emblliig the l^adllut of diph- 
theria in Ji mii:m}>rAno\iii narti tliront whiclt ww ac 
compiuiicd by ttiv<^ro s^nuptomfi, there ccmid be no 
Vflv?rmg in the cIccIaIoil 1o nse antitoxin. 


In 18S4 Carle and Rattone domonetrated tb« 

infi^tiouunp^tft of telaiiUK by Intieululirjg the pua 
from on infected wound into rabbits; 11 of tho H 
inoculfltod TAbbitfl died of tatflniiM. In iSSfi the 
bacUlua was discovered by KlcoUier, and Eituato 
cultivated It oitiflciaLly in IBSd. 

The orgaaUm is rallKT I^jii^j und Hlruder (2 lo 
4 microns long, 0.3 to 0.1> broad), po»0c«M« monj 
fl3g(?|]n And haa a Binail amount of motiU^. It 
vtniuK rcaditv with the ordttiArt nnitia dyci» and bj 
QraiDB mothod. In yonng ciaUuneg tKotnt^d ccUi 
aiid Uireude preilominate. but after a few daym 
sporo foimitiQn bc^cna; eventually oil tlie adult 
rallfl dflgen<?rate And t^io culture conaifits i?ntirely 
of spores. Tbe eporca ba^t a larger diameter than 
tbo bacillue, an? situated at ooe ond of the coll and 
givp UiP latter flie diaraflteristic "dniinsticle* 
form. The orgauiam is a strict Anaerobe and » 
obtainod in piure culture with some diffloulty. 
Uorphologicall/ it is ilifTic^ult to diHtitiguish from 
the booiUi of malignant etiema and symptomatic 

Few organianua ore distributed more widely and 
g«n«ronily than the baciIloB of tctanun» It ta most 



■buadant in 8tr«ct rlirt and in tilled groimil wliich 
hu been fortiliBcd with manuro. Ntcoloior found 
it lu twelve out of L'igliteL'Ji ftitmpTea of earlh. It 
19 \cea obumfnitt in timber land. Such 5 distribu- 
tion is easily EtccoiirLtcd for, ejnce tli« bnciUuE 
seeiiid nonrmllj tu l>^ an inliubUiitit of t1ie iiiicfiti- 
cftl tract of ttkc 1;ot»c, cow and elieep, oud is often 
found ill thitt fif inai\ hikI other nniranls. It -30 
curfi on dirty clothing ncd readily gaiua access to 
dweliiiiga with dust in vliich it may be bloNva and 
cairiifd wbuiiL Tetanus frPHLii*tiUy di-vi?3upji in 
gunshot wounds in whirh dirty clothing [9 carried 
into tho tiittiOj and Keveml insuncea of Iaouw 
fctanu^ hflvr bti-u noted in which a number ol" iii- 
dividunlst iu tho f^imc dwelling have contended the 
difieaw folb\ring injury. Particular localities may 
t>e heavily Infected, Id certain tronicnl diatrictn a 
largo pcn^entjGc L>f ntnvborri infiintK dit* lyf ttinnoe 
neonatorum, ixnd puorperal trtanua has prevailed 
alanninslv in Bombay. It h(i§ been aiijjgeatrd 
Ihat tht' vviplom of hk'Li>Piinjf th^.^ linrn on llic 
ground may bo responsible for the prevalence of 
the liiecoae )n th«6^ localitioa, bnt from the fact 
that it hcut decreflacd under A.wjitic priictici!^ the 
l^crnl lack of aut^cai precautions is probably of 
gr»tj?r impnrtnrrc. Telanns has reaiilted from 
ibe injection of impure gelatin for hemor^tatic 
pnrpoACft. I'ho bocilluft hae bc^cn found in eea 

The ability of the bacillua to proliferate outride 
the unimHl body hnn not been determined. Some 
oblCTvers hold tliat It exists aa a Tegptative orgj:n» 
iviR only in the intejttinal trjict of aninutla, but the 
poaribolity of proliferation in «oit is by ro m^onx 
ndnded, prtlfriilarly vinec it ift ao oflen found in 




I — ociirioa vith orguimft vhidi tre knovxi to 

I teoff iti gravtb. WImb JntJiMted u ootid n** 

I iiuy readilj dad tke uMcrobk conditioiu wludi 

' An dwinmiirf for gvuisftttoo of tba afiofm 

Ttv ifsm uv Tvij nautaxtt. Id odb iBriance 
tfagr rauiatd Timkot for «ltvai yc»n oo a splia- 
tw of vood. TIm^t DBAy be killed in six dajs bj 
direct simligbL In compdrijon vith no&-apoii«- 
Coniuif brpiucBi they are tot? lukCADt to aztti- 
iepdcK. KitMito fbmd that tiwy wm kilM id 
6te inisnteB br itc«m, in fiftoca boon b j * 6 per 
eenL cuboUc add, in two boan b j 5 per c«qL 
CATbotic add to which OJ per cent, of bvdro* 
dUonc ecid vw added, in tbroe bonre bj 1 to tOOO 
oerfodf« aubUiMta and la thbty minute by the 
oaino eotuboo to wbich 0.1 per ocai bjdradiloric 
add bad boon added. 

Totiuiiis ia ctm&picwmdy a wound iclectioii and 
tti«rm*'^HMrh that it dei'clopa «o fre^neatlT from wounda wbidi 
arp oontaminatad witb cArtb u readily uudentood 
from tbe di^ributioD of the organianu aa dted 
abore. Considermg. hoverer, the great nntnbtir of 
%VKh voaodii And Uw pfer»len«e of U^ bicilEus, 
tbe rarity of ibo diacaK ia remarkable. Id expU- 
natian of this fact Invottigations have ehovna that 
llw oi:gani»in l» not a vj^rou^ punutiLe, tTint it 
daaauukdi apccial conditiooa for ib clcvclopiiicnt in 
&e tiioues^ Ao«ording to Vailljird and Rouget. 
tho siporta whea uiL^Kf^d friT nf loxin iln iiai mntr 
totan\)s, but mthcr aro taken up and destroyed by 

The bacillus, fartliermore, h a strict ana^robfii 
*^**' w"*«'nl*" dcmandiniT for its dcixlopmcoat n wound from 
wbieh the ^rie largely «xclud^ It is w«Il known 



cosDrriOTfs or lyFEcrtos. 


thnt penetratiug vtouucIa in which infeotcil luu- 
t«r[al is carried beneRlh the (Q»cm. as the rui^y 
uftil wouitda, also Uioac accompotiicd hy deep lao 
cnliont, o wounili! i^ifliolcd with hhmlc oiiriridg(<«, 
or those in which dirt and micro- orgn-nimis have 
been ground into thd ttsBUce, as id cruabmiz inju- 
rifli, ari* pmoy in le followed by tetunu^, [Tnder 
inch conditions thr bAcillua Uca deeply tmbod4G<) 
in t)ie tmae^s and remote from the flir. 

Of fqtijil imporUinrp is the prp«eii(% of f>rei^a i»iiit»uaau or 
mAitcr ncd particularly of ofJier tmcro-orgamsnM. 
ficlativoly <uper£cial wounds in which there is 
laceration cf tht tissue with coiieefiuent necroais, 
aa m wounde by toy pifitola, ovon the pftpor-cap 
ptitol, are veil adapt^ for tho d«Te]opm«nt of 
tctiiitUA if the germ* wtTc en tho *lrin at the time 
of jnjiirj'. N<i(rrotic tis*tie favora tb« proiifOTatioD 
of the letanujit bflcillr in twu wava. In the Hrat 
place it 6cula up tho vound to /t certain extent, 
and thua providt'g Uxq riN]uiaito anaorohlc condi* 
tlon; ID the second place it wouh] seem to prevent 
pbagocytoaifl of the bae^lh in some obscure way. 
Tt hu« bt*n *n^;'<.'*flUvJ thnt f;hp etrong, ohomotacttc 
relation which c.^ciats between necrotic mat^nal 
and laucocytes caiisea the Utlor to lake up tbo dead 
tiMim nitlirr tliJin thi- hiirilli Tliut itirmi^'nl fi-tr- 
eign material may favor the clevelopment of teta- 
Bua in 1h« presence of iho microbes wna (shown by 
Vaillard and Rouget: lelanus would develop in 
the prf^cncc of an aptificially produced hcmalonna 

V or n Biiboutanmiiis frietur^ while in the absence of 

I irurh pn-dinpojiiiit^ fnciorn Ihc- liMirilli wen: l^ken lip 

I by p)iagot-ytea 

I Saprophytic orjEaniBraa find lh« pus-prod ueinff y*'*^. 

^ coeri which an* uinally found in woundK conlfloii- 



nntciE with earth appear to faror tbc <l«Tclopn«ilt 
of tctontu. This may be explain<i[] to «omc intent 
bj tlieir ■bility to iccreaM tlie Tirul«nc« of tbc 
tetanus tMictlluff, a condition which is rt^tod i& cal- 
tunw. In th<? vmiiul Ihi-y maif c!ri£ii^ the leili:i>- 
eytf* in pliugocvtoai^ and pfCTcnt injrwtion of the 
tctanuA bacilli. A« aerobic orgftnUma ther nuy 
fadlitfttc dcTcIopmcni of tbc hncilli by coiwumtnf: 
looftl oxyg^. 

Our great harvest of tetfinua fulUiwmg Fi^nrtb* 
of-JtJiy injnrirtf in clo»cly oMonatrd in the first 
placfj with thf» nnrm, ilry HE^aHnn in whitrh the 
bflcilli arc more readily dlaacmiiiatcJ with durt> 
Olid ia the tctond place wiili the nature of the 
ivoiiik! and mijed infedmnsc, im d^-Hcribed nboire. 

UcojuionoUy IctnittiA fol loirs tbc simplest 
woTimle. which may hjire heilod entirely before 
0yiiiptom£i detoJop. In "idiopatbic tetattua" and 
in the *o-palIcil "tetaniu rheuiuaticns/' which fol- 
1[}Wj^ «j:|io»an: tn t:ijld, the iiifi.-ct]oi] atria HTc un- 
knuwD. In thc> lutkr inetnucc a Intent infcctioa, 
wbicn U siirrod into nctiviiy by the reduction cf 
raiistanci; wbieh oftCD folbvra exposure, may be 
prevoiLt; avLTuleut tetanuA baoitit (?) »orc culti- 
vnlril from Mie lungs of one such pnlient. The oo 
Cfldonal occvrrcDCc of t^titniis following diphthe- 
ria aud typboij sugg^te that infection may tuktr 
plDCC tbrougi) isouDtla of nmcouo gurfacea. NeiUier 
tbc bncillLks nor its toxir;3 penetrate the nnbroken 
eltln or mucous membrnnes,. and the alimentary 
tract i» further protctted by the ability of the gaa- 
tric and pancreatic juices to iligcGi the toxin. 

Tbp inenbnliou pmoil viinea from two or throe 
day* lo neverol vrceka. In tbe atatiatica of Rose SO 
p0T cent, of the cases ebowcd eymptoma in the first 




aeek, 45 per rent in tl^e B^^c^>nl^ Jim^ nhttat ^(i pi'-r 
ct-nt. ill ilitf third or foiirlli wooke. The ehortor 
ihf inc]]bHtio:i pcriorl the more ftt\n\ the iWwAS^. 
In the AtAtinticji c'\tet\ the mortality vriih nKort iC' 
tmbfltion ^va« 01 per cant.; whrni th« inoubntioii 
period voA moderate ft waA dl.3 per ci*i)t., ani] 
wheji prolon^d, 52.9 per cent The niiaror the 
iiifwrlion HtrhrTi) is fn tlie «*ntriil rrervous *v»tein 
the shorter i* The inculjoHon period; "head tcla- 
vt\f^ develops qiitcJcly. 

The jwitlnigpnic propt^rti'ca of llio tf^tunu^ bacil- 
lus rctiiJc ill itH aoltiblt^ tojln*). of which two. Uta- 
iiwpUMiiin and tctonolyiiD, arc known. The char- 
ndprinUr mTvtwn phenom^aii cf the infection de- 
pend on the action of the former, whcreaa the kt- 
ler, a liCTnolytie toxia. is of minor importnnce. As 
in diphthfTin, n Hvetemlc distribution of the bacilli 
18 not ncfc^Jiry (or tho iJcvclopmcnt of the dic- 
eaae, Ihe toi:in hfring produced by the organi^mti in 
the vouod, whence it m carried to the nervous 
tiwuc by wnr of the lymphatics- Parlicukrly iri 
luUed infections tetantiA bacilli may he carried to 
ncif;:h boring lymphatic j^landa and eventually 
r<yich Ihp drcuUtion; pury eiiUHroa have beun ob- 
tained from the hcnrt'ft bbod in experimental 
nrork. The blood, on accoiuit of ite contonl in 
ax>:gen, ia thought to be unfairarahk fur the 
growth of the orffanism. 

Just bofor? donth tho toxic hsa boon demon- 
ittrated in the blood of man by injecting »oine of 
thc^ lerum into mice. lU excretion in the urine i» 
quoetionabK'. Tetfinua producea no cbaraoteriatio 
minitun'ic. cbaiigea, altliough dt^j^euerulivu leuiona 
in the jcuif^lionic odJs occur 13eath uauallj occur* 
train asphyxiA cfinAod by contractlond of th^ dia- 

phrngm, or miucles of the glottis, cr from cardiac 
faJliiTtv fn »omc ififttnnwn tiie blootl 1ia« beeo 
found more oi 1cm Inked btxiiuBC of the nction of 
the UAaiiolyeiD. 

Trrlnniis loxm (tetanospanniD) has & very 
rirong oflmitj fcr titc nt^Tvoua tJaaiie of suecepUble 
aninialf^ Tliii niAy bo cIciiionEtraled in Uet-tube 
ex{M?riffieiits tn whSdi the loiin ie mued with an 
cmtilaiou of the Ecrvoaa tiflaue; the iii^nouA ti^ue 
noutriUiatJi Ihc loxin more or lea* completely, u 
delormined hy subiequent inoculiitionfi of the mix- 
ture (Wa*8CTTii Aim's exjieriment). Tt is WO l»y 
rr-rtnin nuthonfic* tlmt the toxin attackji ouly tbc 
ultvous Umuo in m*ui; m *omo of tho lower ani- 
mals, howpriir, various organs, eap&riaMy the Hvflr, 
have oil aOinity for tic toxin. 

Tho method by whiffh tctnnus iokiq reaches the 
pcntr&l nervou* *yiitem liiu been llic lubjuot of 
much spPciiTntioD and ex|)erim@nta|{oii. Hecent 
ot>Krvation« br Unrie tin^ Morox and by Itantiom 
and Mevcr »hov tv^Ui a groat decree of probabil- 
ity that It Ift absorbed by the end orgotu of Uic 
molor nerve* and from (iicre pa:(&e« to the gang^ 
lionio cdia through the oxia o^'Iindcrs. Tliu ab-* 
aoTption tftkos plac« very quickly; nhen tho toxin 
ia \^h^a ijjtraveaou»ly it iliBoppesira from thf? bloud 
in the course of mioutco. It has been found in tiic 
nervo* within on hour and a half after auboutone- 
0H9 iiijfciioti. Il* further traiismie^ion ceotrftlly 
occupioA more time and, indeed, the iaveatigators 
mentioned explain tba rathsr long incubation 
ptTJod at llu? diaeiutf oji the UautH of Uie time re- 
quired for thia transmiasicn. The brief incuba- 
tion period in '*hoad tctanusj^ accordingly, would 



depend on iht ihort diituico tho toxin 10 obliged 
to Irsvd to r^di tlie ganglionic cells. 
Although tlie toxin appears not to Iw iaken up 

by the scnaorr nerves, a painful forro of the dia- 
caee, (ftowa doforosa (Meyer), may he pro- 
duced oiperimentJiilj b/ mjecting tlm toxin into 
the posterior roots of the apiiial nervea. Uoux 
caused *'cerebral tetanaa" by iatroducing the toxin 
intij the CKrebnil ti^ue; the coiidiJion is dmrac- 
temed by ole<iic<; of coutrflcturea. "Local Leto- 
hik/' in which tho tnUBClea in tho ricinity of infec^ 
tioD or iTLoculation are involved in con tract uren, \& 
tho first sTmrtom of tetanus in experimoil &ni- 
mflU; it rarely occur* in man exoept in bead tela- 
nu5i The phetiomvaon depL-nds on the Tuct that 
the toxin, being trunsmitted through the nriolor 
nerves, reochve first the ^nglionic cells which cor- 
respond to the infected HTh&. 

Acconliog to MetehnikcfT^ the only natural im* 
munity which man poaacesos to tctantia ia kuco- 
cytic and tJiia may be sulllcient to protect under 
favorable coiHlition«, The nhservHtitms of VniMard 
and Rougct {cited above) eupport tliia cUim. Su»^ T«rfeDii" " 
eeptibllity depends not only on the preaenee of 
mutable rcccptofh in the ucrvoub tissue, but alao 
on the dejcrcc of [iHinitT which cxista betvden 
tbcce receptors and the toxin. In man and soTne 
anirnaU this afTioity is verj great, uhereaa in fgwls 
it i« vcak and an enormoua atnoort of toxin it re- 
quired to eaiiao tetaone. A further proof of this 
wrak aEVmity in nuQ-suHcepLiblcr aniuuilK reets in 
tlie fftct that the toxitL when iajn?tcd wtc the blood 
moAma mi&bAorbed for a lonjc time, whereaa in 
fOiOeptible animals it diiuippenrs very ijutekly. Ac- 


iSFECTiOx AyD itfjrC'X/rr, 


qojrod immumtf depend* on tk* predenoc of onti* 
tnarn in thp drcnUtioR. 

TeUtiu^ aiititoTiR fn « thoroufftt propliyUetic: 
I'bii f«ct has bc«B lieraldtd so cxtcDHTcly in re* 
ant JBATB that then can be little excuw for ignor- 
anoe ou Uit; pari uf imj- phvniL^dii. At the aame 
time, the rctnms from the *'Fbiiith" abow tiutthe 
principle U not yet d^ply imboddocl in tit« nuxlicftl 
mind. It lA qikite cerUia tliat a lar^ percecU^ 
o( Ibcee fatnliliod ccuH be prevculed b/ two idJoo- 
tiouK of iitilitetnnin Etrurn, nnr st the tintf* of in* 
jury and a Mcond from five ti> eight dajA btcr- 
Aa epidemic of puerperal tetaniu in an obatetrie 
wnnl in Prjigne was cJieckcd by prophylactic injec 
tion^ of the nntttoxin. In a certain acction of 
France 4,000 horsw, with iTijurifs comraanly fnl» 
lowed by tetAUUa, roceiveU antitoxin and none d^ 
volopcd tlie dilate. 

No dcgive of efTiou^ on the part of the anli- 
toxin, howo^or, jtiBtiftcs disregard of the atirgical 
core which the wotmd demands. From the fact* 
cited it is clear that thoiougit and frequent di^iu- 
foction of the woond, trt^ drainage, the removal 
f>f all fnn^iirii nnil rii.'trtitic TniiE^rial. nrul Ihft tc- 
oc** qt ftir ore ineuBures of omint-nt importance 
l*uiictiired CToundg vhonld lie op''T»ec] up. Anti* 
(ojcin. preferably aa a powder, may be xiscti in the 
u'ound, aril the wnim mfTUrnW into the adjacent 

The principlcft which Rppnrcntlv iindcriy the ill 
■ucccttc uf the antitoxin a« a curative Agent were 
treated of in Chapter X>CiI> Part II, Itn udminia- 
trntion nfl cntly t\t> porJBiliJe ofler eymptoma havo 
appeared ia demflndpd. After Kymptomit have ei* 
istcd for more thjin tliirty hours Behring main- 




Ulfis that tberu iu no liopd oF cure by llie huLcuU- 

neooa route. Jnoaniuch as fi>rtj hours or more aro 
required for cotnplple abeorptioii from the subcuta- 
noooa tiseiic, iotrarjiscuJfLr injection of at least the 
flrfit 'Irme voiiM fi*'<'m tfi tie inflicnterl. Yet \\y 
tiftilher of lhc*e tnetlioiifl U lli« mo=t e^entinl eiu! 
aceompli&hod, for tho Antitoxin doc£ not reach the 
nervGA nor cnn it be recognizi^cf [» tlio t^arebroapfnal 
fluid in con^picuoiin qiiflntitir?. The most that 
neh injeoticcB nccompliah i? tlic noutralizatioa of 
the cJrcuiJitin^ tokiti, that which ia not y«t on its 
way to the central neirous ajfitem Ihrougli the rao- 
Tor nerree. It is, of course, important to neulral- 
ixc thecircululiiig iotin and it must he done quiclc- 
\y, for in the eourGC of a few Unnra the fatal quan- 
tity of toxin may have been nhsortiet); "a (los« of 
antitoxin which wcultf joro in the mOTnicg may 
he without effet^t in tJie eTeaing" 

At t)ir Mtma time it i» of i^i'^ntcr immediate im- 
portance to neutralize that wbioh haa already en- 
tered Uie peripheral neiieH, ami if possible ta tear 
tvay 8om& of 1h« toxin already bound by the f^anf;. 
!ionic celln- Tr» nrnropHfih tliii nhjrct. or lo at- 
tempt it, special procedures are domandcd. W* 
may t!i*n consider the arktitojcic treatment aa fol- 

Fint: The neutralisation of the toxin which 
haa already been absorbed try the periplieral ncrvca 
toil apliial eord at a putnt aa near the vita] center? 
■a poftaible. Thia invoKefl aurpcal exposure of the 
large ncrrcfl of the port aa near the trunk aa poiai- 
bta and their inrdlration with antitoiciD (Ransom 
ani) Meyer), and in deaperflte cases the infiltra- 
tion of the antitoxin in the >pmal card in the 
ricintty of the medullary e&ntert. From fiv« to 

M*Bti»d »t 



Hfteeu iitiiiiine mnj he iajixU^ into lh« tivjy% 
tnuUcB Pi a fiitUiif, And the opcratioc loay be re- 
peated on subsequent days; the ii»«dl« iLgTild b« 
partiaUy vitbdrawn anU reioaertel in differeat di- 
rectio&a dunn^ ltii> iiij«'tii>ik. ifogcre rocoramcitda 
tying loDAT H^nt(irv« nmiind the i^ervee filter the 
operation eo that they may be readily drawn up 
and ido^tified for iurther injections. In order to 
rradi the medulla the iatncGreljral method of 
lloux or thnl of Hogora may be utilized. Kochcr 
hiiv. ilcvifiiYl H trchnir^ for ih>? inlracer<'bral iiijei:' 
tion«. Anterior to thd parict^fTontal auturc and 
lo one side of ihe mediaa line the scalp U pie- 
pared, and a liot« tlrilled through the akin and 
ikull, having its dirccticn towar<i the foramen 
mn^tmni. By menns of fl long needle, the rentti* 
do ie penetrated ami the serum, after injection. 
flndB il3 way to the fourth ventricle to the imper- 
iled respiratory ami cardinc renlera; 10 c.<% raaj 
bo injected, lloj^crs seeks to aceompliBli the eamo 
en3 by a different leehnb? He inlrodneea the 
needle between the sixth and aerenth cervical vcr* 
Xf-brm. pnncturea the cord deeply, and injcet* from 
20 to 30 mintnns nt a 0il6ng. Although there is 
doogcr of intrttspinal hemorrhafe in the proce- 
dure, no ill eifccU w^rc noted, U haa been reeom- 
jnended alsQ that the cerebrospinal flnid be with- 
dran-n by ineana of lumbar puncture and auhsti- 
tuted by flntitoxin. Sf*niG phygjcians who have 
used thin moihcul report favorable resjilts. 

Second: The uoutraliKatiou of all toxin whidi 
ie not yet bound by the norvoue tiasuc or absorbed 
by thif mntor nerves. Thip demanik the icfUtm- 
tion of the wound and eiirrounding tiasus with the 
entitosiDf and injection of a suffieienl amount ol 


■■r*«««^ Tlid diaetM ott«n eqwckllj in lonw European 
"•""^ diftrieto in which impropertjr pTtcerved or raw 

applied \9 & vimiiar or icJeotic^ diiooc which is 
«tiif«d in itiuai« by altad iwh. In 18^3 ^n 
Brinaa^b iavcBtigatecl « liam Hhidi Uatl camxt^J 
50 CUM of botnlUai, uid leolatcd from it ta aani^' 
r^W, fpor^fonnidg bacilhu, whicli produce • 
•olnblc loxin apible of caiulng tbr entire sjnnp* 
tna-compJcx of tbo diictic^ The ortcncism pot^ 
9tmti fligellv, hsa limltecl motility, gto^rs only ia 
Alkaline tncdiA, ^a^ In orntrut to iriOiil patliogeoic 
orgaoisiu prcfuts a ntittiT«lj tow ti^in]>crAtqro 
(l&i«* C ). It It prob«i% <M) Ad-iiMni of iU 
phjnolo^c activity at ftich tcrnpi^raturcft tJiat it 
ie able to produce its toxia m mcaU which bavo 
htvii kupt in 41 ix3o1 ftsux. ll ia fni^Htl in Jtvorii* 
poMd buD and variolas Mosagca (l>?b&rwnr»1 and 
Bliitwnnt), tmA pnbMy ^ns nc^'oss tn llic mi-'at 
after tlio aniinal baa been killed. Von Krn)':n- 
^om iiiT«lifcftted two hama froin the &im« aiiimAL 
On« wft!% iir<!fr miA^mMr comliticrns bving noTvred 
wilii brine, while the other was exposed to air; 
oqI^ llie fonn«r was toiic- The organiem^ may bO 
absent fram Uie superficinl portion of the meat, 
but abnndaiit in tho doep portioQ. The aporea arc 
relnlivrTy BiiiBt^rptihlr l« hrnt, Iwitig Hestmyrsl by 
a trniptTiitiirc of 80* V, for one hour- Aside from 
ilaocrHrrpnrfrin moat, nothing is Icnown f>f the 11 'e 
hiitlory of Iht^ bacillua, 
T«Hin. The dincaee is cnnsod by the toxin which haa ol- 
rea<iy b'^nn produced in thi? mpflt find not hv the 

1, iHh^r (WlhiiciTitr nrriahmn. (iliwldllr a. fitteituau 
■pil ff, nil cnmmvti*. tbd KCtriElf tFif pA'tlj^plli^lil blli:ll- 

liii anip iiPTEi roiinri in ptiivmoui meats. TIic (rmt 
VritniJInnt rormvrt^ wph appHird td tfcrl«ia forqA of meAE 



aotivitj of Uic orgADiflm after it has reached the 
alimenUry Irni^ (v. Ermengem). If an rartract 
of the mcfll is made vitli wat<?r and the bactma 
removed from the latter by filtration, the liuiil 
uliow-g chttrarLeHstJp toxicity ((tr imimals. Thia 
experiment may be used for dctcTmining the prca- 
enpo of Imtiili^Tii toxin m euepected mMt, The 
guinea-pie is the most tuaccptJlilc animal. 

According to v, Ermeng^m, the bacillua does not 
proliferate in the boily, nor doea it proiluce toiln 
rigorously nt body terapcratnre ; hence, he coasid- 
ere it to be a atricl eaprophyte — a pathogemo sap- 

Tho toxin is lahcn up by the circulation from 
the alimeatary tract and la not deetroyed by th9 
g**trio and pamTeatio juices, didering ia this re- 
spect from the toiin« of diphtheria and tetanus. 
It ii prepared artificially tiy growing the organiam 
nnai^rohi cully in miitable hQitillon iind subsequently 
^rilisizig the Jluid b; Jiltration. Like the other 
aoKthle bacterial Inxins^ it t^ ausccptible to the ae- 
tion ^f flir and light, nnci i; di'etroyrd by A tciii- 
pvrature of from UO to 70'^ C. 

That thu toxin haa a special afTjuity for Uie iierv* 
oua timuea ia evid^t from the aymptom« of the 
diseaae; hiatologieally, tkjo gangliouie oella ahovr 
ilcgeneratitjn iiL fntal caa^s, t^riikiicir ot a 
utrong aHinity between the toxin and ncrvoua tianic 
Iie« in the ability of the latter to nmitralixe the 
toxin in the teftt-glaw< Tlie toxin, however, ap- 
pcfire not to be £o adectiTc id ita action on the 
nervous lisMue ns thr lovin nf IHnnuR^ for in hot- 
uUam dcgcncratioDa of the glandular orgona, and 
of the vaaealar mdothelinm odth conaeqnent hem- 
orrhago are characteristic anntemic iindlngi. 



t^rKcrfivx A Tin iat uussty. 

Uan appear* lo txr very Muiicoptiblc to Uitt inboxica- 
tion, vherooa doga, rBte, and cat* ore rolatiTely im- 
mune. Th« toxin tu palliog^i^ 1>^ subeiitan^na or 
intra vOBCiUar injection- 

Aivijivlin^ to V. Kri(i<^ri^v.'nT, tlu» Imcilli uh^'ii iu- 
oculaiei) Aubeulaucoualj do not proliferate* but arc 
talc«n up b^ the phaKocjt» immcdiat«lir or after 
thoy hti\9t boon nnrn«id to other organs. AnlmalK 
vliich liave wcoyercd from infection or wbicli have 
been immuniscii acquire mUior atrong imrauni^ 
to jitjh*iMtU[;Eit iuDcnktionu, tlic iinmuEiitj htrin^ 
ft*r«rkfii>-i< Tlio prophykctit^ raeaniKA coodst in the avoid- 
** tnmttC ancp of |M)(irIy prwrnt^d ami iraproperly cooked 
mcati, especially caunntiECfl^ Llotuliam would KCm 
to he very mrv in this country where rnw m**flU 
are not iJ*ed estcreively, 

TliG antitoxin (Kcmpnor) hoa proved of aonM 
vatiirr in animal 4>i peri men t^, but ite coTomerdal 
proparation haa not been warranted oq account of 
the rnritv ct U^e difoase. 


Kiir a long timer tt was thought that the '*bncillua 
of blua pus" waa of no importance aa an infectioua 
agont for man, although its pathogenicity for ani- 
maU hm\ lieaa recogniicd tsxperinicnl-iilly, Tt ia 
found vith #omc frcfjuoncy in the blood mid op- 

fsna of man at autopey, vhen d^aith baa resulted 
ram eoms other infeclioci or chrome dloeaEi?, and 
in euch tnatanocs it ia Jtuppoecd th^b a Go-cnllcd 
*'Bgorm] ttiviwidu'' by th(? orguntsm bng occ^urrf^d. 
I>uring recent ycaxB. however, acTcral coace of pri- 
mni^' pyocyaneut aepticemia have been otwerved, 
tlte haHlluf having hec!n obtaincil from tho h!ood 



in pure cultured tluring lif« or from the blooi! and 
organs shortly oiter death. It has bocn found as 
the sijle orgUTiism in meningiUs iLnd vegetative eii< 
docartUtis- Scnne of the C5*es indicate, bovever, 
that a previou« lowering of resistance, Gta that 
caufied by lubETCuloaia and «jp1ti1Is. h ImporlAnt 
for ga:eral invaeion by the bocilluB. It haa been 
foimtl sevcrnl times in flnppHralive processes in the 
iuidt]Ic i.-ar. aniJ v^diiM ^etiJi lo be either (lie musu 
or a strOD^j adjuvant in some oaacB of severe enter- 
if,;a, i!speciiil]y in ebiltlprn. In syHtemie infeo- 
tiona, the flym|)tonis are ivphoiflal in eharacter, 
with hiph tempcrataro, ditirviifa and a tendency 
to the formation of hemorrhages in the sUn auid 
internal organs. 

The Bacitlua pyoqjaneus ia ffidoly di«tTtbuted 
and tlial it cumo* »u ft* iufocLioiu U probably due 
to ita low pathogenic poH«r. It ii vn organiam of 
roanifoM activjtioe. !t producca a tubfltance, pyo- 
ryanin, wbich. when enpoeed 1o the flir fiBsnirifK a 
bluish tint« and on uhicb Ih^ coW at the pud de- 
pen<Iai pyocyanln Is Boluble in chloroform, from 
which it niny be precipitated in crystAlUno form, 
Undor proper conditmnd the i>r^aniam alao formfa 
a ^iioet*iVi'til pigmeut. It products 3 ^trouz pt^p' 
tonimg f«rmciit, coaguUW milk, and in old 
ooltona an autolylic fena&nt ia found which di- 
gc»t« many of the laciOi. Aa atatvd in a previous 
dttpter, Emmerich and L5wo have idenlilted a 
faotfterlolytlc femient. pywaniiK*?, whieh dtA4aln*ii 
the anthrax bi:c:IliiK nnd othrr organisms, Th* 
farmcnt nature of thlR tub*tanc« ii In aomo doubt, 
inMmucli aa it rfsiata the boiling teuiperatar«, 
Dietrich tliioke ita action is due to tho production 
of oiimotte chungM. Old cijlturvji ci^nUin a lucno- 

Hfl 1fA«lf4l4 



isrtscTioy and iMnuyify. 

lytic agGDt (pyocjanoljrsin) of an ftlkaHD^ ziatur^p 
wludi rttivU boiliug aud It not t true toiio^ ainc« 
immimiiatiou vith it docs not yield on nntitoxiii 
{Jordan]. In B^ldilioD to the prailucts ni«iit*onM. 
(he oq^ciKm »ecTctea a irue tiolublc toxin for 
vixich it ist poff^bU to obUin nn Aotitoxio, and 
powESfiefi. furtJiermore. an endotoxlD for w))ieh 
on antitoxin can not bo obtained' 

T]i« wlijhie toxin of Bafiitus pt/oofati^m is not 
produced in large amonaU. It differs trcm tht 
Other aolnbli? Ioijua in iU r««iatuna! to iK^at^ vith* 
■landing n (prnpE-Ttitun* »f 100" C. for fiv^ min* 
ntci> It produce* the symptoniA which arc char- 
aderistio of infection with tho living organi«n»] 
tlie priiicifud auaUimiir duiii^ Udu^ parcnchymi 
tout dc^ocrations and ccchrTno»c«<, the Utter np- 
poMdly bein^ due to degeneratiTO changes in the 
endotbeliuui of the vesaelA. 

By immuniunf; with yoim^! cruUui^ grown on 
an n^ar «ijrfm*e, a senmi which 13 hflctfrieidal 
and opAooic ia obtalnod. On the otiitr hand* 
if an older tcxincomtaimng bouillon culturo ba 
uwdp the wcnun i>^ opHinie, hactvrTtidnt ^md 
■ntitoxic. The scrum whicii is hactericida! and 
opsonic ha« no pov«r of neutralizing the toTtn. 
Tho toxin #oli)tinn i>ant(iins not rinly th^ tiiia 
toxin, bat also quantitica of fndotoxin which 
wero Hberatod a< tho dead bactUi wore diatolrcd. 
InaiRmurh a; the flnlitoKin ripittnilifefi nrdy the 
truo toiin, leaving tlie ondotosin unbound, tho 
toxicity of tho ftltrnte cannot Eie destroyed entirdj 
Ij antitoxin, a condition ^hich i» broagbt out 
dourly when the nttt^mpt ia irmde to ucutral' 
h% a multiple of tfiu* t^imple fata! doge hy tho 
rorreKpondtng amount of ftdtitoiin, In such mill- 

OTa^n Toxiy0. 


linUi fl fatal ani'>ui]t of «ndoU>]cin w pmont. 
Alth<rag}i a strong niLtito^in mny be obUtne^, ft 
would appear to lio of liltic pracltctl inpoTtiizicc 
becnitfl^:- of tho rerlij of infodioui ljy llifl Imcillua, 
Infection in inao lias cauj*eil Uie foniiatiiin cf 

rtitlnin In KCvornl irnitancpc^ but it hM hoc^ 
nt in nthprs. An Rgglutinating senim i^ read- 
ily produced by artiftoial imrauaiEation, 


Soluble tojiinfi, of fierhiips wcondnry inipor- 
Uncc, whtch aro prwliiccrl hy the sliiphjlorocciis 
and fltreptococcus, yrill be considered in Uic sectioni 
deating wiUi these organisms. It eeenis probable 
that tlicy do not lepre^cnt tbe eascntial toiic 
Agmta of the cocci, but rather that the toxicity of 
IftttpT dqjundt ebicily or tbe action of «ml(i* 


Dunbar GoparAtcd from tito pollen of Tariom 
grains a toxin wliich la able tc precipitate tjiiicaJ 
attaolca of ha> fever in tto^e wtio ate euecGpttble, 
haTing first UeTuonKl rated that Uie etude poUena 
Cftuee the diseoae. Tbc pollen from tlie following 
aro said to contain tbo toxin ; Hye, barley, wh^at, 
muLze ((!v>in], do^s tail, couch-grasa^ millet, Hoe 
and some others. The ao-caUed atitnmn-cotflrrh 
which U c-timmon In Amerir^a mwy bo due to a 
aliglitly different toocin coming from tbo golden- 
rod, rag-weed, and perhaps other autumna] flover- 
in^ Ijritiiitf. 

The toxin n^ualW Ih afieocmted with certain tii« T4iIi 
itareh-lihe granuLea which are contained in the 

polli'j], but it t%xun alw m polUais tvhicli do not 
contain thcM ^axkolce. It may be cztractcnj with 
vatcr or uU volubon, ii pnci|]itatod b^ alcohol, 
rfstMt* ihn boiling li^mpiTatiirc, ami is of an a1* 
bumiaotw luturc. 

When tbfl €nid« polloa reodm tho conjuoctivft, 
pB<4*a«A4«i«> iijuifti or liriJiichinl miicoii« membrane of fiusf^ 
tiblo milividunl^ the Uaait ia dudoK'f^ oat by the 
t«'r4*(tOD« luiil abaorlxvl hy the lymptintJM, Wh«n 
a|q>1ied to \hf conjunrtiva it c&Ufte A«r<>niiTj:. n^l- 
nCM and InohnmAtion. It i^ carried bj the toira 
to tbo nat4t «nH ht^rv cau*w txc9*m^ iMTCtion, 
Awdlinit of the mucous membrane and nteenng. 
It miij boconi« dintnbtitiHl i^ycli^mieallr on u r<4aih 
of abeorption ffom tin? frw »nrf8PPii ntid raiiHG the 
Aitlimatic attacica and f^eral \vmptonia ythic-h are 
n^Ji m th& intoxication. When injor-tod labmita- 
niHrnaly uito tbi' anr botb the AAllimatio BUat^k* 
and coTjE^i^likc ^ymptoma fvr-rc produced. 
^niMoiir DuDbflr*3 antitcxic aenini (pollantin) ia ob- 
rroiiWfiUoiH tiLitjrcJ iiy immunixin^ lioiBCH wllh the tojcin^ It 
aMtna to be of undoubted value in a certain per- 
cciitaf:^ of easM, but fnile unaccoitnfuMy At t[m«a. 
It la. pcrbapa, moat effective when used in the 
prodromal etftp?. the attack* boinij ttiertby pro- 
voDled. Ila failure in ctrtnin innUuiriw muy be 
duo in pnrt to the inofficacy of the aDtitoiin 
a^inst tin? toxinu of cerlaSn pollena. Again, in 
mrtain imlfvfJual* *lie aiTlnity of the toxiti for 
th* tiMuCi may be unimually prcflt ho timt a mora 
Vi/^roiu use of ih^ rpnunlv Is demanded. 

I^flbbart. nnd Prsiiii-Tiite published statietica of 
?Sr» cnscs. of whioh fiS wcrr autumnal, In ordi- 
nary hay-fcvcr tJic wruui gar* positive rwiiUB in 
ar pair cent., partially pwitive in 32 per cent, and 



nc^'ative results in 11 per ccot. of the coacs. In 
aulumnal catfirrii, 70 per cent, were positive, 19 
per cent, parliullj' poutivc, and 11 per cent^ zeg%* 

The small bodies of nntitoxin ore ne^mp&iueA 
by A pipette with which from one to several drop* 
mfty be inKtilleil into tho e^e or tlio nose. 

The wrnm <he* not cure jiermnijentlj noJ ouu 
who ia auaceptiblc ^ould carry a vial for imEno- 
dint* use durinfl ^e linj'-fevor K'Oion. Repented 
UK of thi« wrum ha» l>ec^ cbieived to ro#iiTf in 
eeneitLffltion of tlie pntioat to horse «»ninD. Dun- 
(hit rrrommeml* in thi'tc enwtt thnt a very dilute 
ft^lution he Mwd, 

Inha1attoD» of inercaftinj; omounLi of pnllvn^ 
bp|£iniitn>! Willi vi*ry mimilp ijimiililirp^ ha* n]*rt 
been trial witii tlic i(l«a of active iintiiimuuitioii. 

It ti probAbli* thut further Mtudy of buy fpver 
nr H ph^'Oomfnon of onapliylnxi^ will rptiih in the 
e:iplanation of pointf cort-eming the ilfaciae wliirh 
Me not vet cle«r. 

11. innmt plakt toxikb. 

HicuL from Uie 6ee»ls of RtWrii^** c&mmtitth; 
tbrin, from Abru* pntatori'nx : notin from the 
W<tdi9 rtf C-rrtiim tiifJitim, am] mhin, from tJie leavPi 
and bark of tlic locuat tree (HoHrm pai;udtHuccia) 
are chiiTfty of exporimerilnl intcnvt. Thoy ar^ 
similar in Itreir notion, are very toiic to nnimiiK 
producing both local and f:enGril chnnjE^ vith 
fatal termination wbon given in mffieient doses; 
lliey Uttvi? pruiiouiit'ed a^^lutiimling ftctiun on the 
errthrocytce of moet cnimala, and in some in- 
itoneea are KU^htly hemolytte. By guarded Lm- 
rouDizalion antltoxiES may he olvlained for tlienx. 

ffalj. F^woi^ J»fa (VM). FU]Hn 
iivcr; tatk for ikiaali and b stim^ bemoljttc 
toan^yD^dL Bf iMwiia i w rinn Part htt »- 
«nll7 lUiiwri u flslSlum lASA sratnliKB the 

or <U u. pnC«eli lalMii^aA fir* faUl dote* 
of tW Inik n* torn a aa aqMiMM eitrvt of 


I- ronoxn^ mr nun Bttw. 

n* poMQ ipfantttt of dttJcm <v»mM< of 
m ac cr rtofy ^Htd on eadi aide vluch cmninTmi' 
cata ^tib a Wbdar Faag t? BcaBa of a duct Id 
the pasBfn state tfa* faap atv dmrtrd badEvard 
OB Ilia root of tba motttlif bvt wIicm tbo aaiiaal 
strjte teSr poiati aia lude to project forvard 
and tl»e poiaaii li forced throqgh the catiala bjr 
mtucular coiiipreaoMii of the aac, Th% tODOia ia 
a glandular aocfvUcM. T1i9 colobridlor, anoii^ 
vhadi 10 the Anwrkaa coval viak«, poescaa im* 
moTftblc faiijy;i; 

Tbo moiTW of different Boakm rary a gnat 
deal in their toxio propcitiea. The moet impor- 
tant eondtitueikU are those vhicb attack the ntm- 
ovs Atvli-m (n«iiroloxia)r Uj>? I^xhI (mrpuaclat 
(hcEaolj:^nft ami hcmagglutinma) and the endo- 
thelhUD of the btood vecwLi, eniufng hemorrhageo 
(hanorHiafrlcp an eDdolheliotoxiii). The three are 



The Dcuroloiin cfiuBQs death by paralyaia of the 
canliac find respiratory centers. The liemoljsbi 
appcen to be of tcnii importance ru b c&ufte of 

Tiic venome of Uie cobr^, waler-iDOCi:fl£in, da- variAOomb 
boU and eomo poisouous Eca-soakefi ore casoQtiall; r-roiivriivs 
neurutojtic, nlUiough they have strong dieaolviug Tu*!*-''"" 
poverfl for Ihc erythrocytes of some imiirala. In 
Studying tiie hemolytic powers of the veuoins of 
cobra, copperlieaJ anj rattteHnake, Flexner aad 
Ko^chi found cobra vpnom to be the nioet hemo- 
Ijiic ftnd Uiat of tlie ratt]f«nate llie least. Thej 
ftttribute the toiidty of rnttlesunke poison chiefly 
to Qie action of hemoTrhflgin. The same authors 
atutlled tike action of dllF^reut venonia on the cdU 
of vnrioTB atiimale and by abeorption cxporimenta 
tomx^ inclependent oytotoiinB for the teslia, liver, 
Idrlney and blood. Not only was there a dietinct 
cyfotoxin for etch organ of an ainmul. but nl^o 
for the same orgnn of OiiTerent flnimnls^ resulta 
vbicli tpcak for a remarkable complexity of 
venom. Certain r^nOTna contain a l«aeocytk 

ITiat vonorns contaia proteolytic ferments is f*»— •••^ 
ahown by tlieir ability to digeat gclalUi and ftbrin. 
Tbif povcr may be related to the aoftcning of the 
muaolai which has boen oct^ clinically in cases of 
pDLHontug. Tire rapid dej-ompoeitir^ii of Lht- htidy 
vhich foJlova death by tnako- poisoning la assth 
oiat^ with a decrease in the bactericidal power of 
Uie bloody vhich, according to Fleiciier ajid No- 
gfQcbi dcpcnda on fixation of the complement by 
tlie venom. 

The hemolysin and neurotoxin, and prrhape 
other tqftolyaina of venoim. coaaiet of an:boeeptor« 


ijriWfTtOS JLh'B tMUCSlTT. 

III 4*111. 

T*i9Mfl Anil 

which 111 thamfolvr« Art non-toxic; th«v beoomc 
lo:iir only tlirougli 1li^ aiil of oomplt^inenlB which 
arc prcftcnt in the b^y of the poisoned anioul. 
In thu instance, complvmcDt wMch wnuiUr is s 
Murce of prolection bn7citta->ji a nounrT; of djtngffr to 
the finiina] potBcann; it- Not (vaXy does oHjiury 
ft«run]^<!<implEfracDt lerr^ for activation, but Ky« 
'liwovrrc'ri thai crUi (crythroeyles) msy contain 
another kind of complement, an **on^ocompl^ 
lEunt/' which netivnfw the ambm-optor* aftoT the 
latter have conibined with tlic c^^Uh, Flmiier and 
Noirnchi found that thi« al«o wa« the cue vitb 
th« neu rot otic ambor^ptors. 

Tlie nbilit/ of let'ilhiTi (o activate the lipraolytic 
amboceptors of cobra rcnoin and the preparation 
of cobra IcTO^lMO (K>i<e) woro ilencnlwd in I'firt 11, 
Chrtpt^ XVr. In tbfl pnepnintion of eobra-WI- 
tliid tiip neiiiiitoxiri i* ficpsiHled fn>in the hemo- 
Jjniu, the fomjcr rotuaioinj; in solution, whcrca* 
the latter k4Uc4 at a prccipitntc in ci^nibinatiou 
with the tectthin. Immunization with llir nonro. 
io\'ni isolated in tlii* n&j cau«L'0 Ihf.^ funiiaEiDi] 
of ft »peci6c antincurofoxin (KlJiot). The neuro- 
toxin may iil^o bo alwtriU'lw^ from tUf* vunom by 
treaiiiJi; i}\v IjitU'r uilh (hi^ n^rvouH liivuo of ii 
aufceptiblc animal t I^^lcxncr and Noguchi). 

The hcmolypin ie distinct from the hemagglu- 
tinin oud the latter may be eliminated by li«ati]i|E 
the venom lo from Tfi* to 80* C. In the action of 
venom on crythroc>iea oggluti nation precede* hfr 

The Toxin* may be convprti^fl intn rn^oid* by 
heat or treotmont with chcmicula, JmrnuoiKfttion 

it)i toxoids canaca the formation of antitoxtnu. 

SliAKB \EmM. 


Itadiuni la said to <lestroy the toxicity of i«ni>m 

The ajil.ivtnin of CulmcttG is nhtnincd by iin- 
munixing horwa witli a mixture of \enoms (80 
[>er cdDt. ccbra, VO per cent vipenite venom) which 
are alteiiuttfcl l>erore iiijei.'tion. Sit moclhs ate 
requited to proJuct a Btrong serum. T)ie cUim 
of Calicetto that his scrum ie oflectiro agamat all 
iOale-TG&omB U erronoouB. It neutralizes thc«e 
vi^iiunm Ihtf U>iicJty iff wludi Oe()«mIs Wgely on 
ikDUrotoxina nofl hcmolysirF^ bui \m^ little infiu- 
cnc« on ratUcttn^ko poiMTi, tlio caeentiai IqiId of 
which is hBmorrhsgtu. Antin^niii for the rattle- 
■nftkc ADtt wftlcr-mocoasin mny be prepared by im* 
muDiiation v;th tho oorrvapouding M^nontt wbJob 
havp hwn atton^atei] by wak aciclfi, Nogiichl haa 
producvtl wrLiin of juirlj ntnTngth thnt it pnimimK 
to bo of practicdi viiluc in Ihc tn-^atmonl of tnttle- 
iDfl]c« bitce. 

A« inHipnh*f! prt'virniPtly, tlii- Mrtion nf vrnirim it 
prcccdc<l by no apprtfciablt incubation period; 
h«nco. an antitoxin to be elTcctivo muat b? admin- 
julcr*^ not UUt ihnu n few houn aft*r ibc bite 
bu occurred. Noguchl found in relation to anti- 
v«nin for the rattlc^nnkr that the qunntity of anti- 
Ui-\in tit'Cvti'arv to «utv vat qundrnpled tliri^e hour& 
afl^r inlraveiJOi)» inji-ctiun «f lwr» fntal dop<'* of 
rcnom. Fortunately tin; venom i.i lc» toxic vhcn 
introdbocd tfubcutancoualy. 


Phryvoiyain* vrhich ie pr««cnt in the blood and 
ckin of eerlairj lond«, haa bc«D atuiied espeoijilly 
by PrDachiT. It h a tlicrmolabiW, hemolytic toiiQ 



for witich on ^ntitiutii csn be obUioed bj immtiJii* 

Ariohiwljrua, obtAiaed from the bodi«i of cer- 
tain i^tibtn^ ■ « bemoljUc toiin, whkh by immuc- 
bitiQD jkldi ft specific tobt^xin. 

A poMDD, with pTopertif* rflsi'tnbling tlioee of 
mmkc Tcnc^m. maj be obuliwd fn»a tH« caudal 
Mgmoot of Ihc tcorpion. Antitoxin ta prodtKod 
by imiuunijiatioii. 

UbthTOtoii&, A name given to the toxk proper^ 
tJiw of ool MTUin, it ocmpofM! of n nourototic and 
a hemotoxic coikatJtutnt. 

From Iho fioiKQOUEt ^unde of cwtaiii fiih 
^3'f^sMr^^a drtirrt) a highly taxic, thcnnolabilft 
snb^tADcc ifl obtaiimble, for which on antitoxiit can 
bo prepared lij the {mmu&itation of mbbita 

GROUP 11. 

AcuU infectious dtseutti cauKcd by badtiria 
wliich do not seorete strong 8okb1e toxins in cul* 
lure mcdU, but Vfhlch coDUb eiidotoxinB (toxie 
prqtopJniim), rnfi>ctu>n or immuiiisalion cftutM 
iTinminily of ooDfijiK'ralilc or prclongod fhiTniirtn. 
In utiivc immunity tbc serums eg^lutinalo the 
CDnriponding {^rgnnicmn And nrir protw^tivt* for 
otber ftniiiialb' (uiili-inftcUDiig), Itut have litUc or 
no ciirati^'o power. Th^ formation of antitoxins 
ill not i^rfinitpljy ri*(iiMiith(*rl, Tn rnri*t itwiiirici** 
TAcci nation bas bf^cn accomplished, Clinicnlly 
th?re ii leucotytoffia in *onns Inatancea and hypo- 
Icufopvtom in othfjns (typWd and Maltn fcrcr). 

A. Tba soruni i"n acquired inmitnitr/ is incrooifd 
in htirtrripiiial and opsonic power. 

BbertJi first saw liaciVus typhosus in micro* 
■CQpic preparations of the nie$entcric: lirntph gl^'^i^ 
tnd Gpleen of a typboid pjitient, in ISBO. Koch 
also obw^rved it at abimt tb^ ^iiie ttme, anil 
ttai^cd it in the inteatind wn\[j tq^lccn, liver and 
Icidney. It was obtained in pure cnltuno bj Gnfflcy 
in 18&4. 

'J*hc orjjfaDinn is rckd-sliopcct, 0.5 to 0.8. by from 
1 to ^ roirronft in dimpnaicitift, witb nothing Hfnr- 
ftd«ri«tic iu its morpbology. Tt poflseasea from tea 

Tbl« b«« DOt bMn MUbUiliaa In rar«>d ta MtJU tmf. 


lyFXQTioy AJfD tUMVyiTY. 




td twelve flagolla ftituit«^ iit the end* and on tiu: 

siil^s unf] 18 uctiv?]y inotfle iiiitler ^ultalile condi- 
lione. Jl forma ii'> spores and ]g readily cultivflled 
ciQ manj media. 

Tlic bccillu» i* on*.' of tlie intJicr nuiiitrout "in- 
tatinsl iH'^up" <^' or^'nniBiuB, oertftiu iriembcrr of 
irhich are so HtmiTjir that tla*j t'mi br iliJTori-ntmtfil 
only hy mf*nn of *ppcinl culture*, ntiimal Cipcri- 
mf^ntg, or Uip n^hitinating, opsonic ^ind bActori- 
cidttl nctioii of B|jetMfiu Imimiue m*rumn,' 

Tin" orfiflaiem tme lip^n cultirntr*! frrun earth 
und ijifocHpd wjit"?r, nnii from Ihp focc*, urin*. 
bliioi], ri)M-'44pote ami tTte vnTinii'^ or^in^ iif tvpliciij 
ptiticnU. In muny inctanrt^ in ftliich an epidemic 
hna certainly bv«ft cntiePil bj nn infwtod v^aUr i:up- 
ply altejiipte to i-ullivate tlic* bacJtluh fraui tlie 
water have faikd, Tlif or^-anipnifi (nu> not hove 
bwn inHinU'iT in tb<' jiiimpT^^ whiHi wpfp nnalpod, 
or, whot Ji; equally prolijiblc in ci^iUin LDfttADi^a. 
they Jiave diM out in tho water by tie timo the 
divKUDti* Will* K^ wMra[HMnl nt it\ ^^^ riiM*i<lfml r-pi- 
dcmie. It^ occnrrcfiec in Nflture dcpccde on the 
^S#tribution of ihe evcrotions of the palicnt* and 
rflrri^'rs. Thi* viability ntid \inili>ricu (if Ihr- bariK 
vuibiiirr iuB in vrater, cnrth, fXc., vary with tho nfltvjre of 
\U flurroiindtng^ Tl baa bG«n found to live 
for periods of frojr 8 to 4 weeks to 2 or 3 
monthe in water, frofjj S to 1 nonthe in njiTk, 
from 3 to *i montlH in Mirfao<* wMtf^r and from 
11 to ](> montba ir Ktcvili^ed earth: I'M) da^ 
in iee. from I^ to 30 days in «yftere, from 50 to 


2, or Tbii croup iFifl oni^fiii or aficbicrr, paTtrpDbold 

tmrlllirB. Jl-^r.iVvn rrttrrtftiStr i\t Gnrlmtr, rnliiu luirlllim Hml 
ififfJTut art'4r%mif v. 111 aildtikiu to ihe cyp^oLC baclllLe. ire 
Ihf mniit Injinartfint Ifcniinv of Hivfr r^lmllor BiorphDluick nnd 
VDlinral [>raprr1[** »nd tbe pk ihotvnli^Kf of nrtiln of Ihem. 




80 diys wht^n ririni or cUitliirifir. nnrl for 3 month* 
Id typhoid fetes. AVlitn m valer or moifit eaith 
vfiich n^nUin nnny fnprophytos iu lifo i« %h<tTi- 
tued. ll durvivL-f (Ir^'iQ^ for rnan^ month!, al- 
tboLj;:li iliret't Miiitigbt kiLle in the i^our«e i>r a fow 

Thdt thn trpiioiil Im^illuB socrotoi a aoliibl« 
to%in, has nut \tven rtAii^taettivily (l^n^onsl rated. It 
CDDtaiDfi. Ijowr-vcT. OE cndotoija which mnr be 
ol^iriotl m polution by Iho OLitolytic ili;.'tHtion of 
CulCnrei, by eitracting giciiiirl-up baciiU or by 
M|Un.'>;inc OiK Uu^ iilnnnin undrr liiirb jirrawiirc. Up 
to the |jrOtf«it timt, imniuni^atiori with none of 
thoo propBffltiorp hBfl tP^Hlted in Ihc proiluction 
of nil iuilili>xi<! )i(*ru]n uf ncrtplcM] thIuu. 

TVpIioid fcTCr may b«cGine epidemic eitbet Tn*j"<>M 
throi]|jh a contaiiiinntcd wotor an*! footT supply or " *" 
by winfiul inrfV'tion. Wbrti t\uv to irifiv'te^l water 
ther^ IB ftomtthicg characteristic About tho eip]o» 
tmhicft middt^nncNri with wbich dmcnp or *Tcn hiiu- 
dreds are stricken within a short porioJ. The water 
of rtrpHTTiJip BMiJill lukpii t'T vt^e i'\fiirn niny bprnnie 
infi><rtod fr<jni nn ilI't^nHtruittd out-lioiife, or from 
di&rhargfs which have been thrown on the ^^und 
la Uitir vitunity, Tvphnirl -tnnle thrown on the 
Sronnd adjacent to wtlU havo t-nust^d email e^o- 
dvmin. yrnit, Tc^otnblcfi nnd milk oan^ nny b« 
ittfecttid by tt'A^hin^ thnn witli euntuminntt'il wutiT, 
and it 3« iTuppo^cd tbnt the difica^e may be ac<^iiired 
flvm oyateri vhiob hove Lam in wotrr eontamU 
nated with vrvngiv 

The importance of tbi* soh<ji1IciI briL'illuA-t^ni'nvr* 
u a lonKe of epidcmtci of typhoid bai beca 
recently emplia«i£4>d by a groat muuy obfervanu 



nrKCTsox axd i^Mnxtrr. 

Park c5tijii«U4 thot from £ to 5 per cent, of nil 
people vh<i rcooTcr from ty^tioid, continuQ to 
exiri-lo tyf>hoJil bfldlU by «■«)■ of lU« uiirmrj or 
filimrntory tr«ct«, I'lrk ^\to utinifttei that oikc 
4^iit of ev«Ty 500 a^ulU ^ho hare n€T«r had 
tjiihoii!.. hnrlmr typhoH] Willi. The hi)r U ^cu- 
croTlT regarded as the medium in \rh\ch the bacilli 
p«Tpetu»io tU'msclve^ in Die <:^t/e of tW csrrkri, 

B^ vrhnt^irTr m^AHf nn sjudcmic U wt in motton 
priniarih't it Is ubuallv a^gravat^ and prolonged 
ly llii? occurtciict of coBtaet infef^liocs (indirect 
contort)- The hnnrU of tJic nurw-, plij^ioinn, or 
otliCTB who come in contact witli tho patient be- 
c^mn onnUniiimletl from tlie aifmh^ uHne, aollcd 
linen or vkin of tho pntit^nt, end the orgtni«ai« 
■ubuquantEv arc traiteft-iT^d to food, drinkiog 
vati^r, or m otl»er iiti iili'nl«I wayn r*^m-h Um mouth. 
Eadi new ciutr it a frcnh focn^ from which infec- 
tion may b« carried to otheie, and the chances of 
milk and food inrL!dion hn^mir ^iratrr as Ihc 
cwOi multiply. When the diReharRcs arc not dis- 
infected or are improperly dinpo9pd of, soil or 
hounr infection may occur and the poMibtlitj 
of tranaminpion by gnrm-ladw duet becomes of 
ini porta riwr. Post infection from drlod urin* 
or fcef^ and drop infection from nnn«^ wnter, 
OT th& apniiim of the patient are theoretical- 
ly ]iUMihI(\ hut would ^letiin in he of minor aig- 
nilicftncc. That llicj may cnrry the organimia 
from open vsult* fir o^nspools and df>pnflii them on 
food or in driuking water haa been cpprw-iated 
in cpid^micd in military campa and cl^vhcrOw] 
Typhoid hnrilli hav& been cultivated from fliw 
whicli were taken ft'om the vicinity of infucted] 



IIA» 4fTl«in 

The b&cilli ^ain accds to the h^dy tiiroiigh 
the Eyicphoid tisffiie of the intestinal tracrt (Pay- 
er's pntcliL"* anrl th<! solitary fo]liclra). The occur- 
rcaec of primnry infccticn of the lunge throogli 
inlifllBlion of luferted duet is poBsibJe. but has 
not b«cn definitely proved. Tc this instance h-phoi^ 
baeiUontiR m:;;ht. oooir cither with or ^pithout 
inlestinal iDfeL'Iion. In the laltei* caai* il wmild 
wcm eMCnt:j:i) that some local le^on exist in 
th» lungn or elfe«rhcro from vhich orgflniem? 
could conatantlj be supplied to tljt IjIohiI Neufdd 
doubts the nbiltty of the typhoid hociritM to pro- 
Uf^nlo in tliD blnod, ii^cflut^ of the i^trring bflrtcri- 
cidal power of flie latter, and comuIerB tint infec- 
tion takv» place thTi^u;;}i the intci^tm^ rvcn in casr^i 
of '^ijphrtid withmi^ infi?*iiniil Inninns " 

Tbe incubation period is euljcct tf> conBiJerable 
Ttriotioiit. In & terwi of cai«d in which the date 
of cjipo*nre was known, iJ2 ppr eenl. slmwaJ s/rap- 
tWBfl in from 20 to 25 dfiya, 2 per rent, in from 14 
to JO da)-*, and ? pr rcmt. Inter than 30 dny*. 

Quickly following lice ^i^rclopment of intestinal i^miniMiiaii 
leeions, tho bacilli reoch the circulation by way D»riiii. 
of the lymphatTc*, niid through thr airtion of the 
bactericidal conFtitucnte of the blood (atnbncq>tor- 
ooaapkmcnt complex and poeeibly Icuoopytefl) ih^y 
are killrtl and di«flo1ved in Ur^ ijuuntitii^ It 
is now gcnemlly believed that cnly tliroiigh tlic 
<U>intef;Tfltion of the bacterial cell* are Oieir toxic 
conntilurnlH fhroim into wlntion in tho body, a 
ci>ndition ^vhich is neceeaarj in oMer that UiC tie- 
taea be injured. InfecUon of the blood stream 
vith lirinjc organinn*, in the ^nr\j ita^ ot'Uhe 
^ataM and proc^iojr Klapeea, occnn in probably 
all the cBBe^. 


lNPKCrto:i ASD lUMUJi^iTW 

h ift poMible to evUb]i«h the ilUamwui of 
ttpboid f^Ttr b>- cultiratifig tlie Udlli frv>m tho 
bkwd, eMn Mi>rv tht muai hnti iltwlopod suf5- 
cunt ag;^ltiiiiiattiig power Ic ctma* dfat^^fi^^l^^^- 
A «nill iaii: of bonlUon U inomUW with fmin 
I to 5 ex. of blood, dnvn from tbe mcdifiu Tein 
of Uw am, and •ftor tvooty-four boun of lii«a* 
batfioo n ftuall purilou of it i« |i)ate^ mil. Ootonie» 
wbtch dcYrlop i>n the pUU« mar be idiMititied by 
Uia Vffual bftrtcnolo^io methods, or th« ajiglutinj* 
Hon t«»t amj b* perfonnf^i with n knovn luiti- 
lypboid Mnnu AfUr from tUe i^'utli ti> the (our- 
trmlh liar tite oifptnisma can rart-ly br rultiTAtLMl 
frou tlio blood; tbo boctcrid^la] Htib«tanc^ and 
ptiif^ocytlo povtr of i\\^ blood msv hav9 so 
inrmtwd br tliiK ttnir- tliat nnruUliliK bacilli nrv 

[|] fr^m one-fourth to 0De*t]iird of ibe caB«e. Id 
iIm third ve«*k, or durini: coiirnl«!drrncr, tht* bncilli 
apfoar in larf^^ imnibcr» in ih^ imno* in vhich 
tli#Y TO>T persist for ntanv wtvk*. According to 
KauJMJf'lT, tbuT arc diachar£ict3 m|o the unnc from 
mHaiUUf foci in tbo kidoetE. 

Manj of tlw ijinptoiiK. fomjilkaiiont^ and se- 
f]ttoli» of t^rpboid ftTTT, 03 thv roio-5pot^ enlarged 
NplMD, bone Icvioiif, and in torn? fnE^tani^s nnrvoug 
Mono atad pnL>uttioiiia. dtrpeni! on tlie dlbtributiou 
of Ibr btcilli. Thid it in contrnj^t to (he conditions 
in dlplvtbcrin nnd ti*tAniiit, in which th« dietribn- 
lion of the bacilli h of little fii^iiftcanw for (bu 
involv^iiif^nt ^f (Mirticulnr orj^nni, Ttw anatomic 
fbanizrx and rliniml nvTnptnniA ang^t thflt the 
lymphoid Uhu? and central nerroua system have 
t spivial Aflinity for thi> toxic conitkuontii of tho 
tjplx^ul lincilli 


Tlio gLX'iiU'St change take place in th(? orgnnii i<;n4oitieiiAi 
(lymphoid) vrhkh coiitaju tlie bacilli meet con- '^"^ 
stEuitly nnd m tlie gr(^at«£t numberf. It ia ]ier« 
thnt Uie t6xic HulitiliLUoe mav he preoetit iu greatest 
cor cent rat ion, ne a conacqucncc of the coatiQuol 
solution of Ihe •^rganism&. Mallory <le«rribes an 
taiormous hyi^erplosia of the cudotheluil cells, Gs- 
peciallj those cF the lymphatic atructurG^, The 
cells HIV plifigocytic, and ffspecliLWy m ih& lymphoid 
tiaeue of the tntealinca and in the mcacntorio 
lymph glfliKla^ englobe And doetroy the lymphoid 
ctdln on a Inr^ scale. It seiMiia pmhal>lT- thab tlic 
aidothoiifil proliferation which has been described 
is due to th^ nither mild l>i»t proliRged apiion i>f 
the diaaolvi^d toxic constilucnte of the typhoid ba- 
dllua; the condUion ifl that-of an inflanimatorj 
hyperplasia. It has been fiuggefiled that the hypo- 
Iciicocytoeis of typhoid fcYcr ie due to the dcatrtio- 
tion of ihf: lyinphot.'yt(« in the lymphoid organH by 
the endothelial phagocyteSv 

Th« gmnuUr and tatty degenerations of th* 
par«nchymatoufi urgana do not differ from thoae 
Ken in many acute infoctioQa, 

The conditioDs in the intestinal tract would 
aeem to favor mixed infectioDB, eepecially by the 
colon bacillua and KtrcptocotcuA, and the primary 
infection probably dwrpascs the reaislanoe to seo 
ondar)' invasion. The role; of the colon bacilliw in 
tjfhoid fever i& perhaps not defij^itdy eetabliahcd, 
aJthough it has been found in the circulation. In 
t^fccssce, and in the urine in caeea of c>aLitjH ac- 
fiomponymg the di^caec. The typhojd iind coEon 
bacilH grow well together. A mixed general in- 
fection with th*' *trcpto(]occus cauwe a grave «p* 
lie condition characteriitcd b>- an irregolar tem* 


txFEvrioy avd wuvnity. 

[vnitun> (:unr. Thie ctmdilion may b^ Oiacovercd 
b]r bbood cultures. It b thought ihftt the Atr^to' 
ooocufl doo» not iQcn«io the toxidt}- of th« Qrphei<l 
bftciUiu^ tliA remit txring rAtli» a mjmniBtioa of 
the jatwdCT ti om of the tvo infi^ctionft. Po«t* 
^hoJdaJ BtippuratioDft are often due to th« itrap* 
tococctu And in mjuiy of tho mctu»1iilic cr>rnplica- 
tiont (pftroUtu, pkurUy, peritonitis, menii^itit, 
oUHs ini^dia) etrpptococcl and sUphylococci have 
bccD found. PDeumococcus pQCumoniA not infn^ 
quently eoinp1icat«s typhoid f^ver, A combioed 
infcfiiioD of fyphnid And malaria is oaJd to otcrtir m 
tJio tropica; Ihc conplkation ie grart. Typhoid 
iod diplvtiieria rmy occur togGlher, and typhoid 
may be supcriaipcved oel acute tnbcrculoeia. 
tium-iir The p«nDd cf ^rcatot duac^pijbitttv to typhoid 
"^nuHtuV^ i* fouml fmm Iht- fifteenth to thi/ Iwt'nfy-flfOi 
yciirs. The rc4ifltaocc of infiint« &ad cliildrcn ia 
not satiBfactorily oxpUin«4, A cortAin amount of 
rruitAuce inherited fiom tlie motli^r may pcrvi«t 
for some yc«n sftor birlh. U ia Icnotm that anti- 
bodies mny pnsA from Ihf nuithpr to the fetus 
through iht pleccctB. Id rory early life the tissues 
may r^^rpoml more cnerj^ticiitly to inctpieiit in- 
fe^tion by the rapid formation nf typhoid aoti- 
bodi», cr the pha^cytic cells may be raorc actire. 
The roDdiliona which render older people leas bu*- 
oeptible fire no better understood, A loss of suit- 
able receptoTfl may have oeeurrcd &o that the tc\ie 
OODStitiients of thfi hndlli fiiu! no onrhoroge in the 
body, or tin* aifinily Ittwaeo the recept--* and Uie 
toxic constituent raay hiiT<^ become lew. Th« in- 
dividnol Jurinp the conree of ypars may hare hem 
gradually iiitiTiiiiii7:i;d by the cntrntice of non- 
pnUiogcnic qunnliliea of the bacilli into the oir- 

\niuraJ a&il 

t^MVJitTY TO TYPU9W 4*1 

culalion. That rcfretimo) to typhoid Infection is 
t^L^cretiaet] by luw ituLrltion and overwork \a a long- 
known fact 

A krgt amount of protcotton is afforded by the 
hydrochloric ncicl of the gastric juice, luiJ it i* im^D»irT 
reaaoDflMe to believe that Bxipprcwion or no insuf- 
ficieat amount of hydrooblonc acid may faror the 
po«Eage of living biicLIU to tlie mteatiuee. Normal 
hmnaa acrum is rather strongly bactericidal for 
tJie typhoid bacilliiB, and the It'iicocytcs ingvst and 
destroy it MetchnikofT aFcribes natural immun- 
ity to tho action of the microphagea^ 

The immunity vhifh follows an attack of uarsiiuih of 
typhoid fever is g^ntrnlly of lon^ duration, but imBiaBitr. 
second nltnokf oratir with some fre^juency, Acoord- 
ilig to Dresrhfvld'ft figures 0.7 per cent, of imlivid- 
uala arc alfcctcd twice. It has been not^d that 
Hmilfd ooramunitiee which have experienced an 
epidemic may remain relatiToly free from tht dis- 
CAM OTcr a period of some years, although nec^h- 
boring ilietHctft niv atlarlced, All the sUHceplible 
^iiAli&TiDgbeil thediMQec, n Mate of temporJirr 
Luoity ia created. 

Acquired Immunily U chameteri^eil by an in- 
creaae of the bflctcricidal amboceptor*, op«onin«, 
aggtutinina and typhoid pny-ipitinfl in the eerum. 
It hflh tieeu shown thh( rt-iviviTy U Hrtuinpauied by 
an increntc in conccntralion of sntibodic*. Bnc- 
tencidal amboceptors reach a concentration two or 
tlifpc timiM that of norniiil dtrum ami thtrn rdurn 
l(radufllly to normal, rcacJiing a Dormal ooncectra- 
tloD in a few mjcths. Opaontns increase in con- 
rnntratioit n* do bnclcrioidjil nrnhnceptorti, but 
remain high for many months. Stone belie%^fl that 
thifl increased jM>tt«r of phagocylona eonntitnlei 


l/Ji^KCrSON .%lfa tUMUJilTY. 

Ihe moit importaot factor in tiie immmiity mnxlt* 
inff from on atUck. 

Thin U not el^ar from th^ clinfcil FtADdpdInt 
because of the liypoleucocytosis nliicli ib Himr- 
wJmt rJmrtteUriatic <>i typhoid — n bypi>I*u(*oryto*ij 
(TJLTii^il rbiefly liv n <iira|ipf'jirfin<N> nf the micro 
phages. It lias been eu^^i^ted Umt our con* 

aminstioTi of Ihfl prifib"?!!*! blo^J, whi^rea^ the^ 
me^ntcrie vctoelft may *how IjypcrleucocytoflU. 
Killor}', howCTTor, found a fllrikiiig flbicfico of 
DiicT'opliAge^ eron in tli« mtcfiinal TeeselA, Con- 
ccfiiinii a tht-ory tliflt tht hyr*f!rploflia of tb* Ijm- 
phciH orgnnii spnpa «= a Fi:bElitnti^ for lh*j hyp^- 
leucocvto&ij^ WL- iiiuy rt-rflll llie findingfi of Mallory 
that thiv hypvn^laaiiL iv chif^fiy oao of aidotbcIiaJ 
cvi\U. Thp» impr^rUnrP of tbt'*r mdolbrliii! rwlls 
for the dcatniction of typhoid bacilli D«da further 
>r«pii»iii«ia. PrnphyUxiH iiliould biggin %ritb tlt« thorough 
(lieiufeclion of tha atoola and nrine of trphoii po* 
ticntA^ nud ttils ahould be oontinuM iintll tbey no 
longer i;unlniii typbciil bAcillJ, It iv not good 
hyfpeao to discharge a pationt until bacteriologic 
«xam!aation of atools aitd virine ahow th^m to bo 
U^t fi-um the orgmiieias. It would bti dttBcult to 
carry out this rigid precaution undor oil condi- 
iiQUv-f buh at, nil (^vcntft the stooU nnd imoo miky be 
dieinfcrtod for a roa*onoblo period, say tbroogh* 
out coiivalEsconce. There la no anfficient reason 
for the lieglect of the bacteriologic examination in 
hospital practice. Theru iu a gro\mj|? eentiniont 
Unit typhoid patients in ho»pitnt« ahoiild to iso* 
latcd in vnrds or room^ in which there is a ^cd 
routine for the illapoaul of infectioua mat«rfala — 



imne, nfoola tuid ^piihim, Soiled tinQTi, the batli 
wftUr of Ivplioitl iwitiLiits, the remnntitA of fonJ 
nnd drink, nnd the eating «t«i»*il? Jhf>dd b© dis- 
infected before removal from the room, NiuBe^ 
or uttcn^uiLtd pliould not o^t or Orink in typhoid 

TIeAametliv]>?ririinin may l>e of xa\ue in j?au»iag 
the di^appcfirniirc of bncilli from the urinv, and 
VxG odTimbitity of imiiig the dnig a^ L routtno 
mi>flBiipe for public sufety is worthy of mii- 

sidi-rrtlloi:. Tin* rouin ^Jiuidd he kept free from 

flic* and CTcnlually it should be clifinfected, prcf- 
QvMv by formalin. During an epidemic, in cng^ 
tht" w«lpr ?<uppK of n t'cimmujiiy i^ nust-pptibli- io 
contamination, all natcr «fle<i f^r drinkinij, wnah- 
iDg of vegefabks and eating iitensile. eboul*! ix- 
boiled, uud that u&rd for general cleaniiig may be 
othorwiiift dtninfected. Tho posaibtlity of dust in< 
fertion nf a liouBe HbmiW noi be difregiirdeil. 

The typhoici carrier rflraaine one of the difRciiU 

bloma of prophylaxU. Thnt onrriera mar b9 

of bacilli by iiiociilaliorL uJUi dead baoillK baa 

not Iwcn yatiitfaotonly dcmorstrnt^^d cic'cpt in 

Rome infitunrpt. Syntemntic df^trction and tti^t- 

mcnt of tlie^fi carrten* i* liatd to carry out. 

There are two methods of specific prophylaxta 
igalntt typhoid : 1, the injection of anlltrplir^ld Ji"b. 
tmionne iteniiti; t, prcTtfiitivc inocLilnticin witli 
killed cultures of tho bodlli. Antityphoid B^nim 
eoafera a fairly strong aud Inimedlate immaiiHy 
vhicb. Jiowevftt, ii of nhort dnrtlion. bccanue of 
th« rapid eliminatir^n of thfl eerum. Ita u^»> aa a 
g^nrraT prinviitiip-o, lliercfbrev ^ noi adirocnled. 

Wright ha« been influrnticl in tho^injf tht? iitib 
IN of prot*ctite inoculfltionA sgnin^t typhoid. Ilia 


lyrMOTtO}! 4>i> lUMUXiTT. 

&r»t upcjiakQnUI work via |mbli6h«d in ]8^> 
Sinoa tKnt time Uw isoirutiticiiu liavi^ bvec ntrri*^ 
OD cztencitcij ic Bri«li«h rrginkcnto ia Icdia »qiI 
Scnith Africa. Th« occvrrtnoo of ty^diotd «mocifi 
tbp iiiociilati^l wuH uiie-haU t)»l iuiic>u{[ tbc unin- 
ocuI«tcd, and thc inocuUticTu redoccd the mat- 
tAlitT of the ifs«aM hy oDfr-half. Ttie protection, 
w far aa known, laata for tuu or more yvnn, it* 
thouich ID soma inftaoccs infoctioD ^» occurred in 
'^ v««i»*, frnni Ihrw to (ix monthr: after Taocination. 

Tile mcUioda of pTCf^TAtioii of the raccinc MXt 
tlahonle in order to inmro itofility and iitARfl[*rd- 
iaition. CuUiireii of the tiHcilliis are groirn Iii 
bouillon for from tircDty-foiir to foitv^^iftit 
hour*, and then stcriLiied at €0 C. Tho contents 
of »cr«rat fU^a ate mucd in order to obtain a 
umform dUlributton of 0Tf:anume, UDd ttundftrd- 
liation i« Lhpn aoromplicihiid bj OAHmnting tho 
uuinber of bidlli in a cubic centimeter uf IJjr iac- 
cine. Hj** purity i* ioFured bv bacter^olo^ torte, 
an^ for profii>rYaUon pb^ol or liquor cwnotia com- 
[Hivitud ia afld«d. 

Wnpht has aljoni^oned hia orlgiDttl metiiod of 
Ktviui; & fiiGf*Io mjcction and noir ncon&HndA tvo 
moderate d<i»*^, wbicb »rc ^Etpu fttnn right lo 
fourUcn daya opart, Tbc firtt do«i include a 
quantit,v of Tftcrino which confaina trom 750.000.- 
OOn to 1,000,000,000 of badlli, tlip wond 1,500,- 
000,000 to 2.000,000,000. Wright finds that "the 
iDOculation of thD«ia qutntn indticea an ample 
- elabojadon of fttktibodic« vitboiit producing anjr 
acToni constitiiliottal rt^ction." The inocnlatione 
mcTPflSe tbp hHftpriciilal, oji^onic and aggltiiimitinj: 
\iOvitt& of tlie wniiu and it i* concindKl that aa 
incrtaafid rctifttanc^o to txi^boid intoxioatfon U 



e^tnbUKhed because the second injection causes 
milder aymplomi than thci firft. The phiiffoo}!^ 
power of the leiicocylei* U raJseil, because of sn 
iDCTCAse in th« "opBODina/' The curvt ot Git nnti- 
bodies u liko thit tiiuilli/ obtnirtcrl by actiw immu- 
nization villi bactei'is, toxins or otW Biibelanccd. 
Ivunediatdy folloivmp the inoculation there fa a 

dwreatr rvm of nomntl nnHtmflir-e, This " 


tive pliase," accorJioi^ to Wriglit, laala Cor froiH 
one to f^vcral dove and eorreeponde to a period of 
iJitrNi^ed HiiBcepiiUlitv. Russell ainl nfliers have 
Lot obeeivcd tliiH p^rrioiJ i»f increased fluficcptibifity. 
It is quiekW followed by a positive phase in ^hiob 
ilie iintibodiea nrd^ correfpondingly, tl^e resistance, 
incrcBfle rapidly. When very amall doeca ar^ 
iidminlstered tJie positiTe pbase may be leeoiini^ed 
aft^r tw-Mity-fmir hoars (Wrlglil). IjOTgC doBcs 
cauae a prolonged n curative phaso and arc to h« 
avoid «1. 

Following injection, "tlie local iymptoina fimt 
make ibem&elvos felt afcer an interval of two or 
thn-H! hour*. The elTm-lj^ then steri me the develrtp- 
ment of a red bingh and mrtrc or less bctous eiuda- 
tion »t the site of inoealation^ followed by some 
lymphanf^U* along llie lymplinlica *hicb lent], nt*- 
cording as the Toccine hns been inoculated above 
or below the inidd!o line of tbe trunk, in the direc- 
tion o[ the glands of Ibe aicilltn or of the groan. 
. . < Even aorere icflammation bae never led on 
to suppuration." The exudate ia wnic'trhAt htrtii* 
orrKngk, and the pain Taric» from moderate lo 
frevere, but is not of lon^ duration. Witb th6 
ti^ebnce aa recommemltHl ut present, "tbe i^nnvliiu- 
liora! *Tmnt'»m« arc limited to Bomc beadnche and 
to two or tljree hours of real malaiae* . < . The 



iyFtortos ASD t^Muxiry, 


mxt diy lii* tcmpcrtture comes down to nomtJ, 
tiki be fork coinpartlivdj wdl Ox»pt in rwpod 
to iMiD at III* scut of jt»9culaLioB.'^ 0/ 5,47;* mI- 
di<« vfttcinoUd Ag&uut tjpbcitd, twc«tj-oo© tooJi 
thtr iJfwn^and tv^ died. T& G^tiJD Mldiare under 
timiiat ^mditioni who wH;e iiut vHiTrinated, than 
w^nj 1ST ooMi and tveat^-«ix deaths (F^ehh- 
in«Qn>. Tlie mdliud of vaocinittOD lued by Jfos- 
wll and luj ft!«MaAtn id the U. S. Anny la liiniUr 
(0 that t>f Vk'ngiii, but thr« injctrtioni t«i daye 
npart un> giveii. ll^r llnct of 500 raiUion, tb« ooodnd 
and third of one billion. Xo bad rwnilts hnvr 
owwrrrd in 8,510 ensci, and tho rwuJte have boen 
salisfaclory, not a ui\^h case of typhoid opcurrinfj 
Id any oJic whoM vaccination waa complebvl. 
Among Ihe itnprotftUHl in the annf SOO casce 
dfvclopmJ in the ?nmc period of time. 

Ttie vaccine won prupAKd av followa: A non> 
vlrul*nt utrain nf thi> bacilhis ia grown on ai!«r, 
planted in fUrkt ior twcnt.r-foiir limir*. Tlw 
xrowtJ) ii Lhtrn cmulKiJicd in lolt solution and 
*tHndjirdixpd fji cmjiain 1 billion bacilli to 1 c-C. 
The vaccina la tli«i irtpniitrd hy hcnting to .Ifi* 
C for one hour; 0.2-5 per iNjnt. tricrtfol ia added 
lu u preiervEilive find the »ferility te«led by arrobn 
nnd ananiobic cnlinxw. Th? hnrmkwncss is proved 
bv inoculation into £fuinea-pi^ and mice. 

Thp ndoption of Hntitvplioid inotniktion or vae- 
cinntion undtr certain con^iitioDS appCEre to he 
warrantod. Tjphoid never Ims bi*i>n a world peet; 
hut in the pre§erce oi ppidi'inirn in di'nsnTj popu- 
lated diatricla, the mpOiod may well be considered. 
The <|Q«tion in a pi>rtiuvnt ono aUo for those t'ltioa 
In trhieh typho»l is ^o rilmnivr os in hr calleil 
pndemic. It ha< a distinct field in thr? protcclroii 



of l4v>uiJ4 it] time of \var, whwu it ia didlcult to 
(Aicrvo other propb^^liictic mouur^ and nhould 
recommend iteelf to pb}^idaiiA and nitre^s dtiring 

The products of ontcdi^c^tioD of typhoid cul- 
tures have been ^ugge^ted aa Buitnbte vaccine 
(Nelsaer jtiid Shiga). Tlje toctJ re^tbu itt natd 
to be mild, and the body reacts by the formatioD 
uf barter] 4.' idal ambrx^ptci'^ iki>d agglntinini^ 

Bactmddal senimjt ohbiint*d by thi; imtntinj/n- Hfraiiivriivr. 
tion of horewi with tjplioid bacilli liavc nol Aliou-n 
iliMinct curntive properties. Cliantemewi? im- 
inuniKcs hoTscB with n typhoid "toxirf* ivliidi ift 
prepnr^ri hv gTowing Ihe orgnniBifi iti a liqiiid fuU 
ture Bbif.h contamB an emuUioti of feplenk' IUbub, 
One cubj<: (centimeter of thifi toxin n^ill kill a 
gnin^-pig, n done whir^h in t?oin|ian«on with 
othflr bActerial ioxim \a very weak. CtLantemeaae 
htt uiAd hin ontitoxit^ i*i?mm in tlir trcatni(>nt of 
rnorp Ihiiii TiOO pntipnU, rflpoHirg a mnrtality of 
about 6 per cent,, whercaa that umocfr untrent^iS 
piilieniK wa* from 10 pur CL*nt. to J3 per otnl. 
Alllioiigli n»e»i(? ilgiiri'fi indii-nte *'iTrie wilni? for the 
Mfurn, it has had little trial oulmdtf of France, 

MncFadym and Kuwlnnd immnniicn hoiw?* s^ilh 
extract* of typhoid hncilJi, which hft\i? been giound 
up while Ihey wtr<T kept in a brilUe slate by Iht* 
tcTnpt>riituri> of Tiipiii) Piir, Although ntititoth- ami 
bactoricidal piopcrtica arc claimed for the serum, 
there II no conclusive evidence that it difTort from 
bftcit^^riridttl Hnnim fin'piirrd in thn ordinnry wrv. 

Jez produces a high decree of immunity in rab- ^r*iHi«iiini 
bilji by Artificial tmmunitatlon vUh llir^ typhoid 
bacilTuF. thm prrpmrn an c:ttnict from the spleen, 
bom- mnnow, brain. clc». Of Ibe immuoi^ i^ni- 

/Al'ICCTiOJV AJrO llrtfCT-V/n' 


Biids. Thb tOLtxwA m »dm>iii0t«rvd hj moutlu Jesc 
ji»tiiies thii nwtbod, from the f»ct that tbo Ijni- 
pboid OT^ui« hvTC b««n rfiom to form tjphi^ 
afiUbcidi» (WuaerrnaBtk). Phmu th« dinkv of 
Etchortt iiid oth^n ftTortbJe Tcporti cmocniiag 
th« rvm^j hive b(«n pnbllilk^. ft hn had iia 
extawTe bm. Th^ pr«pantKiD ia niad« bj due 
Sorum lutttttlc of Bcrno dud ii oxptmivc. The 
Hiifi^tion of Fr&enker], th^t Ijptioid pitienU be 
tTMl»d bv *Tiba)taneoa9 injcftiofis of unall quui- 
tilicR of kJMcd typhoid biclili in oir^cr to barton 
t1i«- fonitatioo of aotiboli^ ha* Vtq kept tliT^ 
thfo^jlh the 'typholn" of P«raa<?!j)cy, btjt bu not 
hftd prnf'lirfll Irinl. Of ■ dnittiiT nMturv t* tlie vng- 
l^oa of nic]iardM>ii, that tbc ffltr»t«a of typhoid 
eoltane be injected, Bichardeon reportt Q&ettb- 
fai'triry mutbt wilh vnrioiiH prvpaniiiinK of t^rphoiil 
bacilli, indudtn^ the iioc-toiic split products of 

Arii^nr-t hAs conoluilctl froiti hi« n^sults following 
the ii^jtctions of killH trphoicl bacilli, thai tho 
pruci'diirc is of valu« onlv in capcs of rela|Ke and 
in bflrillu^cAirier* in titiitt to rid th(» peraon of 
the baciTlk Uoncs of from 2B to £0 million bidlli 
vreTt Tised and the iiijeotmnfl w^re rq^eated e¥«Ty 
tlirce dny** 

Tho principlofl and toclmic of th« nggtotinfltion 
test were iltsciibtfl in Part X. Tlitf spiuui 
commonly becomi^ ngghitinating on from the 
Bpvf^nth to the t^rth day^ rnr^Iy as early a& the 
iii*coiHi or Ihirdj and us late as from the tweiititth 
to the fortieth day. The power ia liieheat dtiring 
coiiTaIe9cn)F«, when It may apf^liitfcate in i\\\n- 
tionn u btgh na 1 to dflOi or bigher, and from 
that time ainks j^nditally. An agj^lntimtio^ 




poinr of I i<i l<in hut ofim iuvn fimnJ nt eight 
nKmthi^ nml cjf I Id h'jO ofti^r froui si'vcu and one- 
half to eleven ycarv; but the Utter [lurntion ia not 
the ntl«. In -pt^ricTming tho t**t, n Perum dilution 
of licit li» tlinn 1 bi 40, nr 1 tn 5f> plmultl be 
obsrrved na [irrvimmlv *el foitb, 

Tho following eourcce of cnor ore to be home 
in mint\ : TypboM fi>v**r ooriiniftrfllly nins its 
CinirsH witliiJHt tin* fi>rtnnti<iit of a^glalinins; Hie 
rtaction mav niy^U'rioti^ly be abecut ^ne day to 
nxmr a f«w dovB Int^v, a oondftion whicb indicntea 
the (Tiipnrliiu'i' nf r*>p™ti*(I itvU; rniher high Bg- 
glutinatin^ fjoffii^r ioi tlic typhoid bacilbis ocui- 
BJonAlly dovL'[o|ia in oti»i.'r tnfcctiona* as pDcunio- 
niii, mrniiigilts ii'tpniK, WriTu iliiiciiw, I'lc; the 
poaeibiUty of ^oup agglutination, for tbe positive 
dlmiDntion ot whicPi coutr^^E 1«tit4 with rclntid or- 
^ni)(in« niflj bp ili'iii^ude'V In thk' Tip^Htivc 
roflulU Aro obtoinod irk fi Eiitepidous oat^e. tbo rcac* 
tion* ihoubl bcr tH*^il witti the jiarntyplioid bnciUi, 
The t«t of tbe bflctcricidfll jMiwcr* of tfie htuui 
hftB been rccoiriiiiordod a^ a eubetitntc for the ag- 
glutination rt'iitfion, but: tbe tt'diiiir i« *o m»di 
more complicated that the mdlind will probflhly 
not como mto gonora! iiai% For diagnosis pn'viont^ 
to thi? fnnnaJiori of 'iig/tluiiiuiirt. blood-nilliirp* 
ahould be made an dc^rib«d in a proccdin^ para- 


In 1000 Schc^tmiitlor cultivated from the blood 
of f\x9 "typhoid" patiecta organism!* vhifh dilTor 
froim tbo tj^boid hacilkft in tbnt tbey attack dt^x- 
tfo^ with ^? fomiattcn and ai^ not apglutmatod 
Sn high dilulifjii M ndtilviihciid wnim. Sirco 

■ till 



then, uniilar ctsefl Iiave lii^eii ivfiartnl and two 
^rpGfl of the pATOtyphiod bftciUua liave becai jmo^ 
nixc'd (SciiDttrntHlcrr). Bacilli of Qroap B cvnte 
lint fill aoid roActian ii) milk which chasgei 
to a |>ei niftoentl/ alkaJijae rB4eti<iu iii nbout ton 
daips, whcrou those of GTOup A canse pennoncnt 
ftcidilv (KflyMTT). Thoy referable tho typhoid 
bacillun morphotoglcally, btit mftiirslly flro more 
irloiv-l}' mlflUrcl lu BaciUvft rnUritidur, Orgtmiump 
vhidi hare frrmoufllv hc«n deacribed » "part- 
colon" bacilli (Widal, Gwyn) do not differ from 
those which arv Di?ff rnllpd paratyphoid bacilli, 
and tlie infeirtioiiK cmifrd by them rrwmbled ibe 
rocorded cwc# of patatjphoid fvTer. The term 
"pnntcolcn" ahould so longer bo applied to thorn. 
Paratyphoid fever occurs apcradically or in «pl# 
dernto form, And bc«r» a clofto TmmblaiicCT to mild 
iyphcid-tikc epidemics whidi have hctn noted from 
time to tim(T, aud which, profuniably. art^ eiu»d 
by eating poiaonouB meatB. One suHi ppidemic of 
000 caaes was couMd in SwJtierlAnd in J678 by 
the mcai of a siclc coif; thf mortalitj' was I per 
OQDt A still oldrtr epidemic (1839) h cit<d, lik^- 
wiw c-aup»ed b\ meat Jn both ini»tnncrj» the infec- 
tion crentunlly wan carrii>d from person to person 
bv contact A nvenl uuLhit^ak in KitI, pniviMl Co 
be panlyphoid. i? nuAuinocI by Finchcr to havo been 
cauEoJ by infLvt^d m^jit^on flrt'rmiit of the peculiar 
diatrlbution of tbc ^nt^es among the putmns of n 
particular market Kurth also attributed a amall 
cpldemio to oithor uncooked mrat or millc- Fiadiar 
mvntioDs flf(y ran^a iu Ea>t Holrtcin probjiMy 
caused by the iniJk cf two covf^. Shortly after the 
epidemic began, the poke died and paratyphoid 



/vrwT/ov -I sit tUMrXITT. 

not aU cclla bfjn; tciUed dnhfi^ one boor «t 
ttii« leinp^rttturti. This i»4V expliio the tmct that 
the viron iA aoi vlvay* killol bj cookuix Oie m^AL 
The Di^nUnt probably hoi • wide diptributiooi 
hiTiiiiBP nf ilip w^riimiTKv of thi- infoL-ticni in tan- 
ou* part* of I he vorld. 

Th« toxjrjiy of the bacilli depoudd on lh« ^2Ul- 
vuor of 4 fixdl riiilot€:(m; a mluhtr totio i« nd 
prodnt^. The i^rinciplM of piophyUxis acainst 
Uplioiil fll*"> apply to paratyphoid fever, wlib iImj 
Hflditioii thnt in Die litKrr ^iwsw the |>oa!9it>itif; of 
mcfit infcrtinn mnft be luq^t in mind. 

The »en]m« tif palii*iit« am! hnniLinft^ anImalH 
acquire boclenci4nl, of«or;ic and a^^hitinAtcn^ 
pnw^ni for the <ir^»TiJ&iti, Tbere is no flemm (her- 
up)' far t\\e 'iiitn^-ilon. nor h^A the Dd^aatuii ai'ueu 
to attempt vaccination. 

S«rum fi^ii a paralyphoE^ pAtienI may a^TotU 
iiutc II ic- 1inTiir>li)c:oiij« Imrillui^ in n dihjtiL>n of 
1 HKHl (..I- i/^ixrt} or more (E. H. Kui^diffor). 
u'lioiens the l\plioid badltua U aj:(^]uticflt«d only 
in low djiiitionvi by tht mmo wnirap How- 
ever, bitcillija A and bacilKiB B an? not ideutioal 
in Llu<ir ag^hitiriAbliT propL*rtie!(; ili thU T«jwct 
it JB atiittfi Ihnt the latter in morp clttM^Iy re* 
lat^ to th? 1>-fboi(l bflcillua thaii tho fornittr. 
Tlie uggluliuuUoH le_-<l h t'rtid 1" hnvi? a hi^rWr 
diB^nostio vaUnr thnn the (Jruber-WiJlnl renetion 
in typhniil, n utrfjng^r ngglutinstin^ powi*r being 
devdopeil in the serum of tlie pnticiit. Nevcr^ 
thclrtu, fho fniinntinTt of coiJejjhilin'n* mflv irn^cr 
the te*t cnnfnsinj; if pTf<per spthtii iTitiiticin \* n^t 
prfldircd. OoncliirioTm Hhoiihl rint It ^ttr^mr'ted 
until the te?t Ujia Imrn performed with both MrnvriP 
of the fin rn typhoid hacifhm and vith th« lypfiold 

Dysi^\ri:}iy tt iviLLMH. 


b*et flccompliihcJ bj Ucltriologic cjtainmuljtm of 
th« blood. 


In uddiliou to amebic d^i^cier^', vje Imve Je- 
conm fHiniiiur witli uxx ncute il^scutenu infccLioD 
which appi-nra cpidcmionJly in both tropiuol oiid 
U'rtif^^ral^ cliniJiti'!^, a\\(\ prevaila especially iu tlitf 
stimiiicr miODtiie. Sucb epidemics occur c:itcn^vely 
in Japan, where the inortfiUly may be 24 percf?nt,; 
in the Philippiiif», U(uti:<l &tal(!£, Germany and 
other Kuropcun countneii. In induetnal rietlle- 
menlfl'iii fierrnnny tU* movtnlity U nbcmt 10 per 
crnt. <KriJ5c), The incubation period muy he as 
ehort as two or three dayB. In mild cases ihe pa- 
tient may recover in from lour to eight days^ 
whereas wvcre casoi ladt from two to four weeks, 
and may lenmnnLi? fal^iJl,^. 0(-[:a&!orjully the iii^ 
fection lasts ^ttHieicntly long to bo conaidorod 

In 180S, Shiga, biaing bis conclusions on poai- STelin"" 
live rouultfi with the uggluti nation tc*t and on th« 
coniitanL priwrjcr iif I he orgauisni in tbi' slonU <if 
the inf(^?tcil, iih^ntiticil n^i the caiiso of Ihe diacaae, 
in Japnn, a mipmhe wliich ia knoiAii aa ISaHllus 
Jysonleri^ (Shigal. Flexncr, in 1000, made simi- 
lar ohflprvatlona on ppidemio dycentcry tn Manila, 
%nd hia organiama. or one of tiiem. di(frnn>r iili;^ht* 
ly from that of Shiga, id ealJed fiacithm dyjicntmtt 
(PImtcpr), or thn FWrifT-HarHs hnoillim, FTftrria 
beinjC the name cf a patient from whom this 
lypfeal strain rtaa caltkated. Kruw f [!)01) found 
bolh Ibo Shiffa and Plexner typea in Germany, 
n«dloii3y piving th<* name of "jweitdodyiaenEorv" 
bocilU to the Intlcr, Ja lliis country ainuhir organ- 

454 iKFBVTiO!f AliD lltMUMTY. 

«q„M4>r isnis have been found &b Uie caoea of i&atitittlotul 
t>UTrii*ik>- (Jya^ntery by Veihler and Duval, of summer diar- 
rhcM of infuiilB by Duval imkI Busactt. und br Wol- 
ttein^ It is tlit> belief of VeJ^ler and DuvaI tliat 
acut< dydontery. the work] oiftr, '^whether sporailic, 
inatittitionfll or epiJemie, U caused by th« dy«?n- 
terj bacilluB."' Wc nmsl note, however, Uijit Uie 
orjEttnittn is not fouutl irt al! cases of dinical dy»- 
(mt-Ci7, rvrn bj skilled bacterial ogbts, "Clinical!/, 
24 cf our 07 CASoa in which the dywntcry bncilK 
were fniiitd (li'l not i3i(Trr from th« cne^ of ilmcfiM- 
tis in which the dysentery bacilli were nctt fouocl/' 
(Weaver and oth^r*,) It aeema ceHa^D. n«verUie- 
l<wi, thnt Ii\jnUiL* difscnUria in tbf? mori impor- 
tflnt cfliiw of ncute dyftcnlery. It rarely occurs in 
th^ Ktoota of hi'dltiiy individtuiU. 

The orgAninna cf Shiga and FIciDcr differ in 
th^r AftionA on the fiDgara rnniinite and maltoac 
(i, p.. iu llirir Acid-forminjE powrr^) itu*] in ^heit 
fl^pIiitinnbilHy; the "Fkuner'* t^^e is the stronger 
acid-foriL^r. An urtifioially produced immune S6* 
ram which J* specific for one or^ninn hiw rather 
higher o^rfilutiFifttinjj and bfletfricidnl powera for 
thi* c'nrn"*j«nd:iJif type, but Io\\' for llu- other. In 
thia eovintrv the *"rfcxn*K' hfldlluf ij* much more 
common than that of ^^Shi^a," but here and a1>rfiad 
both tTp**» nni tm-t, nrid miaiclimrt tn Ihi' »ntnr 
indiriduaU Several other oreaniema bAve bwn 
cultivated from dy^pntorie prJli(^ut§, hut the varia- 
tions from Ibo.^e Lwo typea are »llght. All art 
certainly vprj tltwely related. 
ciiifenun*r- '^^ organism is flomewhat thicker than the 
i"*^" "* typlioid bucilluii, but probably ib non-motile, al» 
tljoiiglk Vpdder and Duval^ in oppoeitinn to otben 
(lien1»), riniiii to liavc ikt«'»u^trHto<l dae-lla, U 

UYimA^TKJilf dAVihLUA. 


ofter ahow* a polymorphous spp^ran** in eul- 
lurcb, bill forriLi no aporcj. It is Grflm-iiegalivc 
I( livflfi for from 12 to 17 days when <5ri*d 
(PXuLl) ; Jircct suuli^lit kilU it iti 30 laiuulea, 
1 ycr eeut. phenol in I^O minuted, 5 per cent, phenol 
pliu cniToftivf iiihlimnti.' (l/300f)) nlmniit in*lan- 
Uneoualj. It ia tliouglit tlmt H nia> Vwf over 
vmtor lutd cniu^c fresli otithi'cakd in the #prinjf 

The bacillus is foimd only in the stooU of the j;,'";;!,''^!?*?. 
infected, in the mucous or mnco-hemorrhagie por- 
tions of wLiclj it t'lij^ts rtlinoet in pun* riHiunj, few 
colon biiciJU being in the imniodialG vicinity; it 
hiifi not bctzn found In the blood or urine. In fatal 
ffiies, Sliigfl found it only in the inlcstinnl ukers 
and swollen lymphoid strnctures ard in the mesen- 
ttfricT Ijmpli t'^arKl*. Plexner mentions its occur* 
rcnce in the liver. The organism, if it reaches tha 
rirc^nlutioii at nil, either <Io4*b so in sm:)11 qiiantititi8^ 
or is rapidly tiestroyed by the blood. The infection 
rescrnblofl cholera, but differs from typhoid and 
paratyphoid in this rwpcct. An observation by 
Markwnld (cited by Iif*nti) indiefttea, however, 
that Ihe bacilli may reach the circulationH A 
woman ill with dyseHtt-ry gave biith to a child, 
which died within n few liourn. Dysenteric ohangM 
were found in the inteatineji, mid tlie bncillus of 
dyacnlcry waa ciiltivnted from the diphtheritic dd- 
poiHa en the tnte^titiee, from th» mi^conium and 
from the hparl'ft l>tnod. Tiie or?jkni»MiK miut huve 
[f-ached the cliilJ llirough the placeiitit from th« 
eircu]atii>n of the mother. 

The inleftinol leeions vary from a eimple in- t^atviiai 
fldn^mntorv hvprrpmia rn nftlier rxIrmSvu tHju?rfl- 
eifll oKTotis Uli|>litht-ritii: indamniation)* which 



T^TfXs Mtend» below Ihe aubmiicoaa. St>rh foci 
ftr« ft&iil l<t be the most marhod id tbo detfOMidin^ 
colon HiiJ sij^'inoiil where machanical injury is 
more likdy to occiti. The nccfoiic nrcfu 9VpArat« 
by tloughiDgr It'iLviijg aupertlcinl ulcvri^. Tbo Ivm" 
(ihoiJ folUdt> un? swdUt-n aiid infiltralcrf iritb 
polymorphonudettr k^uoocytctt, whicii &Im flocimu- 
latc in the <Uliil(<(l tympb vpaut'it of ilie intntmal 
wall- l^hc iltiiiri is «o commonly iiivoNinl that th4^ 
condition ifi cnlk<l An il^ocolilis. Contpfcuoui 
diangefi axu not found In tlic mfficctcric glfind* or 
»pl<^D. The liver and kidrjeys commonly fthow 
parencTi_vmafou» degL^neralions, 
Toiipiir vt This OyircnkTv bacilliu is highly toxic Subcu- 
tftiiDoiDt triJccUotift of killed eullurea produce Id 
man a more profotind roactton limn the orgauism 
of aither cholorA or typhoid- Ordinflnr laboratory 
unimab aro m Musccptihic tUdt tlifry arc immaniK^ 
with difficulty; the horec ia loee eiwcqitiblc. Thfl 
toKiHfy of Ihp orgrtnisni apparently deprnd* on an 
intracdlulor t'>xia (an endotoxin) rotlicr than on 
ft sotublo torlD, When liring or killed cuUttres 
are mbmittccl to autodigtttion in mlt solution 
{Conradi« Nc-isrtor and Sbigal. oi- wIil-ei bouJlon 
cultnroa %T^ [iIMvfd lo grow for 30 daya, Ihr 
liquids are found to be toxic nftcr tLtc organinne 
are rennoT«d. In both in^tanoea this toxicity prob- 
ably il:»pt'ndK on ihr lihfTaf.inn of pndntAxins. The 
(incBiion aa lo whctlicr tlio bacilluw in the inti»- 
tiQC« products a »iolublo toxin wbicli ia ahaorhod by 
tbn- lymplinlic^r ia iindptericifir-d. U Ki-vma moK 
probable tfiat the conditionfi are analogoua to tboae 
of cholera, ictoxiCBlion reaultini; from the libera- 
tion of endotoxins by tho 0olv«Dt action of the tia- 
Vi*s nujd« or rdl« on ibo bacilli. T>yAr*nti;ric eymp* 




and .^iHH-i-ti- 

toma are nol ))r*vliK<.'(l in unimnU by feeding Uio 

Tlia stooU of the iiatienl nrc the onlv known ni»i»*»->»inn- 
source i^f the organism ann it continues to be ex- 
crdcd durbg convulcscenca Ijatent or chronic 
casciB arc a eourco of danger lo a community. Al- 
ilioiigh the conditions oucsidfl the bodv are not 
favorable fnr llic growtli of the organism^ it may 
rcrnflin living and vinitcnt for ac^veral montlu. The 
methods of infL-ction uppflflr ifUntical with thoB^ 
in typjjmtl. Wak'r iiifiH'tltin »i'<'ma cti'tHiii, nnA 
indirect Ir^n^MiiH^Jon i* accoinpliaherl ly i^ontad 
with the djacbarpofl, The be?t examples of oontnct 
infectifjn nre Uwin^l in inrtilHtinnnl ^pidemj;^, 

Tht' first «4HeTitml for prophylaxis \^ correct (Ji- rr<i|kiiTin«i 
aj^oeis, for vrhich the agglutination teet and boc- 
tcri^logic ciaminatjon of the stools are cascncial. 
Diflinfpd.ioii ami other precuntions should lie prac- 
ticed OB rigidly as in tjpboi<l. The patient fihould 
not bo diachnrgefi until the stwia arc free from 
dywntory bacjlii. 

Poorly nmtri«he<l imHviiltiflU an? partii-HiWly 
auateptible to infection, and among them the mor- 
tality is hijrh* Tho dieeaeo is most common among 
yoanj^ children, oM people, and Ihoae who are eon- 
^ei;l in inalttutiona- The conditions in Japan, 
liotvrvcr, where from June to December of one year 
nearly 30,000 i^ero attacked, and in Germany, 
where eeven? cpideniica or<:xir in itidiimnal cum* 
munilies, indicnte that cm:4ceptibilil/ U quite gcn- 
tral. Digoatkve disturbance and enteritia from 
other cansra ars said to bp pr^dupcKin^ factmv, 
TIjc normal aerums of man and flmmals have rery 
Httic bactericidal power for dywnfcry bacilli. 




Bii III I Ittiilhepw*. 
m mUA TTiiwifliil |tn<- 

«aft 3» ten* iia iMwCBm 
tkt toiiD, bot 

tk^luni fdttd 

Joohl la bi <hc icrirtetf rf > trw otantric tcnmi. 
Ihc Tite rf |«lwtiv« tWMttlitioai i* not md 
cilabfiiM. SUfB St «av timr pncind mii^ 
m^n Bud pasMre unflnomiin f%«c3fi filvs im* 
Mfvtn) OD 10,000 isdHidoAlf. Th^ dia do! 
lb* tumfcfr nf bif«ct*ons alUno^ ■ lomr 
mdriditr raalteL Slus> «>■»• thai Ac flien- 
peotic me of hid etnun T«>1nrf« th^ DMrtalitr to 
OW^hird thai of tlie iiiitreat*d. Thv mnm of 
BTfittp. ind aUo tiiit of B«nrth»l, iro «iia to be 



jFTuI i\iit roiirw uf tlio ilisonae is ^lorttJIUfd, In thft 
Jf oc^cfd Icr Institute for ^edicnl Ttcscarcli anti- 
dyfccnlerv ecniin proved of no dirtinct value. 

The agglutinatioa reaction writh (he serum oi 
paticnls shrews grcjit varinlnlity. Jt is somotimcB 
absent in spile of th^ presence of bacDIi in ihe 
etools, and often diaappe&TB rapidly during ccn- 
vnlcscouce {in Iwo wooks occaeionally), U is rareh 
HK liigli *iK ill tj'phoid. Fn infflntile diarrhoji* ng- 
glntinins jippcnT at abnitt the end nf tho first wcdf 
of illness (DiiVid and Bassctt). Evidently mild 
COWS ID vbich the course of the disoaee Is from 
four to eight days mav not be rccognizod by ri^qh? 
of tlie flgglulinfition renction before Hip period uf 
coTi\'a]ce<!cncc, In chronic cnecs the aggJutinatij:g 
power tnny fjer^ist for Ihrc?*? or four months. No 
rtaction -vaa obtained with the typhoid bacillua, 
KrUflO considerfi ibe rcnotion diagnostic when it 
occuiB in iL dilution of V^^i Pfuhl, 1/30. Strong 
co-agfilutininH for other opganiama, i, *., above 
1/flO, have not been obtervisl (E^f-ntz). The Lest* 
should nhva^'s he pcrformctl with both the "Shiga" 
and '*FIexi;cr** type-s, tig the two luve not identical 
o^lutinable propertica, siiiil cither organisin inaj 
be Uic cfluee in a ;fivcu inatunce> The obsence of 
tJie reaclioii does tint r-seluih' a dyBeuterie infec- 
tion poAitircly. liocteriolo^c cxomiaation of th€ 
BtooU Li importsnt, often necej^nrj-^ for early din^ 
110(1 Lv 


B6tu)i«D3 i^ & EpcGial form of meat pomcn^ 
lug and the or^Uftionid prudtietior of piinilyphoid 
bj infected meat*, hflv: been raentionc*]. In 
Addition to tbi^^e, mtyc& or 1«°ta «xt4^nive i^piH^mica. 



/A'r*crfav Aim luttvxrry. 

Mp|M»«d fi> be dM to ptomaine uliicli vterv /ouiu) 
in putrid inMt, h«Tc dcmrred ii<>l iofrcqnentliTt 
tt is now ¥r«]| ««tflbTi<hNl that niort «pi^mni«« of 
Uiifl char^lrr arv rikiLi«il t>j' pfllkogeair bttrt«<ria 
wl}irh arc projoot in iht mefli, putncL <IiH'nrupo»i- 
Uon of th» UHor hpin|^ an initiQvnti«l incii^f^ni. 

OirtncT^ in ISflft, lintl Uit Appartuatty iif ■tuil^^ 
inj; nn fp^^cmic coii^ bj the xiMttt of n c?ow vjikh 
hiir) \twt\ >t1ait^bi4>tvd tn r^irtfimV The ajmpt<»niii 
i)ifrcr<*'1 frr>ni thc«f of botulism or nnratypboid, ai 
ilcfi^ribcd bfflow. n« obtsi&vd from tho ina«cl« and 
*p!wn ot the (^Wf ftiiU from the f|jWii of a man 
wlio had been TatallT poiiwnrfl, ar *>rjnini»nA which 
htfl tincc been lnom» s« BteitUif tnitriMh (Turi- 
npr). Tbe mmr barilluB. or orgarfLuiij whii-h n?- 
Mrmblif it cIwcIVh have been rbtnintyl rcpcofe<llv 
dcirioji timllai' L^phlornleF. brith from tb^ <Tiapected 
meat and ftoin Ibe orgnns in fatnl caf«ii (uitt»- 
tinw, blood, epTccn, eteO- HnpttUki, from n e«m- 
pamtive rtndy of aevwnl ^tniins obtained frwii dif- 
fprriii Hnii«r*, <onclnded thai all art mpirbcrti of a 
closely ivlat<^d pwnp of organipme, th^ Rrmip of 
liUfiflvg rntrnliiiix. }lh eonc^lnM'-n« xv«r« baMvl 
on ciiUiJinl pT€pertiir* and a^irlutitifltior tcat^ 

The typieol crgivnUnj it a aJiori rod. often ovnid 
in *ha|>c, poatcoae* fronj fmir in tvrUr hmy: flas- 
dhi arjd hi« Tnoderote motility. It feimnnt* van* 
ou" *iiKer^ and is not clained by Grain> niM^od. 
V*arlationi: amttrtjf individual idrfiini nivj} not Ive 
di»(iiKtci] here. 

According l« v. Ennmgioinr and also IVriipi^sM, 
it« ptlhogwueilv dei>enda on tbe rJnboTa^ion of a 
ftoluWe hwt hdnt-reMetanl toxin. Bouillon nil- 
tnri*^ ivK-Ut 1ov<! "^IcK '« which fh<* batU^ria liave 
bee^i kilTM bv' bent, nW aimilpr cti!ti4re» from 



whic*h thebactem have been removed by filtmtion. 
ftiff tojtiu for mire aud guinea-pi^ (Drigalaki). 11 
ie aoteworthr» Jmwevcr, that relatively large quiiii- 
titiee of th& boLiilton ware necessary to kill guinea* 
pigs (4.0 c.c.) whidi is in uoatrost to the toiina of 
diplilliona and letanue. The rapidity with which 
ntnptoine develop following the ingestion of in- 
fectBi) meat is a further indication of the c^iet* 
ciice of this soluble toxiu, wliicK it would aeem, ii 
fcrmt^d in coiuideruble qtianttties in tlie mOBt. 
Symptom* oocasJoiially *ievelop eo quickly aa 
to GuggcBt eonic strong moUlUc poisoning. With- 
in fl few lioiira vomiting, violent di^trrhtii and 
eolieky ptiina eet in, followed by more or le« 
collapse, weaknese^ houduoho and cot unoom- 
monly by erythcmntoiis, urticsrinl or ht-rpetic 
ctuptioivB. Fever ie absent or iiiconspicuoua. 
The mortality is not high, from 2 to S per ceot.; 
fonvalcfc'ciice ih sail! to be eIuw. Nephritic and 
cotnrrlifli pneumonia have been noted aa se^iiteltc. 
Autopsy slinWB tlio nnntnmic changes of bh acuLe 
f&strcenlerttU. aomclimca of hemorrJiagic charac- 
ter, with swollen Peyere patches; the large intes* 
iioc is not greatly involved. The spleen may be 
fiwollcn and the kidneys degonernted. The anA- 
tomir flndings urc not spt^eific. 

It huA been shown in numerous instances that 
thf cattle or hordes (Urignlgki) which fumiF^hed 
Oit meat uore 6ick wKh an intestinal or general 
tolcction with BaciUua mUriiidis before they were 
■ItugbleTOd. "In a very large number of eoAen U 
eiiD DC demonstrated that tbe animnic from which 
the meat wa* tikon bed bctii -langhten^d in 
^irtrmis itp lisd ilied nivntly. iiml^ indi^wl, that 
tiicT hjul tin certain iiutancca) died beforf tbtj 




Tbllll In 

ootiia bfl ■lAti^htm^. Wxt often Ihcy gaffer from 
Mpbc ioflucMlor; prvmaa ot from traumalic, 
pnnpvtl or oUier mrU of wcpiicemim, or from 
tahtff UI-U*fin*d p«tboloj^e raodJtioDs which 4re 
aicconipaalrO bjr i^rmploau of «nimtiB or iot^stiiul 
or pninonftry infuunitioiv^ (r. Erm^ngtm). 
SubMqoent infection of tbg meat by Badihii w 
(fritidi*. t. e., «fler iluigbterui^, haa not bo«B 

Th# orgintani ocvare la Lhc blood and rarioo* 
orgiM of infectftt bdIduIs tnd nun. Poisoning 
mott commonJy arises Then the mttt hu bom 
kept for Wi^ral da^-i, vIikJi qsuoIIj ie the com bj 
th« time it is oiade Into Bomo fonn of «oaiaje!C. In 
the mi'unlimc Ihr horilli lini« proHf^rst^ and od* 
dJLioual toxin hu been produced. \u at leant oiic 
inttanci; a certain numticr of p4t]CDtf who ate the 
meat nbife it irag fmb suffored moderate or no 
iDtoxication, whcrvu ihuv: viUo ate it several da)* 
litCT became Yioknlly ill. la an qndcmic caa««d 
by hoTVi moat Drigalaki found that ''onlj tho» 
penona eulTenid from inloxkalion vho ate tho 
meat After it }mi\ Inin fur eiglit ilays or more." 

Tiic iBiffo-orxniii*ni n very resistant to heat 
ami the tomperaCure which u attained in ordinary 
cooking may noE Iw nunifrirnl to kilt the bacteria 
wliicli DTK remote from the aurface. Ktcl in tbi 
event liiat tlkc meat has boen thoronghly stcritut 
UiQ hdal-ivj(UtAitt tfUtin may be prvsent in m£ft>| 
ejont i|uniility to cuutw tbc intoilcutjan^ Sot 
mudi i» knovn concomio^ the dietribution of 
BOffilltii fnUritidis. v, Krmengem auEpecte Uiat 
It may hti n tnctor in poluintitg by oyjtters and flah, 
but thU nniainti undetermined. 



TlM blcod acquires specific ngg^utjnine Juring *««i«n*«ia-- 
tho couttw of iiirwdiou. Even right d&ys »ft^r the 
boguming of evtiipt'Miia ag^lutiuatioik may be ob- 
tained in diktioDB Tumzig froro 1/200 to 1/4000, 
The rtgglotinins Llisappear reiy rapidly. Working 
with artificially prepared immune flciuna, Dri|*al- 
»ki ik'teniiiiu-J llio i'iiRt''nce at cangghii'miiis tot 
typhoid and paratyphoid bacillu 

Wo eboi:ld b<?ar in mind tlio liki^Iilioo^ that 
utvniii poiMiiircl kviUi BiLrillux fntf.ntidis, Ji,« wrl! nit 
by pnrntyphojd bacilli, mt^y be cneounti^red ID 
Aniericfl, bb well aa in foreign coimtriee. 

Banlliis coli, or the colon hiKrUlua, U the lype of 
n large group of organitnie the memljcrs of which 
eliov individual differencet, but poeei^eii certnin 
dominant fcMtupt^s in cominoo. The lypit^a! colon 
bofilliiB feriiicrit^ varioui fU^nm, with the protlur- 
tion of gae^ if e etron^ acid producer and eurdlp« 
milk. It i^ flagellttkd, h^isi miKlerntt* motiliLy and 
doM not fltflin vith Urom'» method. One type or 
Another ill the normal inhabitant of ihe intestinal 
tract of rtmn\ itJiiinals, nnri, nltliough the orgau- 
if mi arc vidrly disseminated in nature, thoir 
nmirrenf? j« relnted directlj or indirectly to the 
distnbutiou of feces. 

It« optimum temperabirg lor growth ie 37' C, 
and above 4fl'* C. it dosft not proliferate, ft h 
kilM at a »4:mpernture of from GO* to Rl* C, in 
from firo to fiftoon minuloE; it i< not killeil by 
Mch low teujperatur^fi as from — SO' to — 84* C 
It resists ub&olu(u ^(^fkv^ntion fj>r pcriodfi vntyinji 
frrm a tvvf days to ficverfd month* (different ob- 
servere). Piroct fiinlifrht kills DO per i^nl, of the 
jrenna in Iwo houn (Killinjr* and Pooltham), And 


tyrmrriitx axd iMMvxtrr. 


BMC^tUe to ordin«rjr anlisrptio^ 
S4ny aiumala arc bactcnd- 
r lb* odlon b«cilln*. 

llw pfiaeipl* thit tiwt «trim irliich mar 
C^tinltd fniin ibe feres of Un? uiir»in^ Hiild 
be coasidett^ ia the trpirol Badtriunt t^i 
\ B j aintainta g lint « roTuUiil tjpit of or- 
k fo«nd wider tbaw (xmditjoiu. It k w<i 
to OMW b«r« m rcLiti^X'tr pure cvlturr. 

Whkin ■ Tvrr short t3n« iittpr binh tbft ot^d- 
km i* fomkd in the inicstitic* of isfanta, and ito 
of iDtmict bM k%m tb* ml^eot of Eoocb 
T« view of ite TWidydiiieiiuiutioai it ia 
to coacdtt of muiy circuiiutmaca 
^kh toor it) tntxtiwe. HATing onct roadi*d 
tbt tttwIiaM. it finda th^ra it« optinmm conditicuu 
fir gnvtb. Tfc« vwU iBtocliiMH in moa art 
ntker fm frooi colon bMJlU tnd otber orgaaliBU 
■• volL 'nti»« perbapo, ia du«, to some extent, to 
ibo aUaliniiT of the medium uvd to tbo rathor 
nfiJ Bov of tbe intaalioal oootcnta at thia point' 
TW ooldB bociUttt rwboa ita maximuBi derelop- 
mant In tbo hl^ inlMtine. whtrv, in fact, the 
vbola Wctiri al flan of tbc intntisci i» moat cod< 

tn Ti^rv of Ihf fact that th^ mton barillna i* h 
nomal inhabitant of tb« int«atin». Ib« conception 
bii oc«utn1 to manjr that it may be of di*tiiict 
nlue to thr cconomir^ citber b«rattF» of lh« nrtioti 
it bad on tftfftain foods Uplittin; of carttohv- 
dntM), 01 b«C4itf^ in tome obtour* way it in- 
tfaancca ravotabljr tli« a«eimilalicn of food^ 01 In 
that it antai^onin* otbvr boctem of distinct pfltW 
l««ii^ poircn «hicb aloo Qmt nonnaliy in the in^ 

FtiyCTioy or coLoy baciiw^- 


tJ>e1in«fl or n-n^h tlit?ni through nccidcnt. Th» is 
tjol the jilftcp to TOneiiler th«e qiie^tiors in detail, 
and tJicy arc on none too dcfjaik n bnpi?. It may 
bo fUtcd, however, thit the colon bAciiiu-t ami nn- 
other clusely ri^Uteil uiganiwm. Bai.illun [luciis] 
a^rotfenes, diKlinctlv cir]tB|:oni,ic the nation of cer- 
tain proti*oIvtir biK-terfa whicli flppeflr to be Anaoci- 
flteii vitli tlie putrid J ei^om position of miUt Aiid 
othoi" proU'iU c^ontaining foods. Bat'tpna of the 
\hiiBT typp pxiiit in ihtt inttvltrm. ITtivteritTwd 
milk ha& n natural rQeiitance io putrid decomposi- 
tion, and eti-riliwd milk to nliith tht' colon hnoiLkie 
or liaritfiiM \Jiirt\-i] arrof/rnr^ hnft hp^^ij addrd, has 
n eioiilor lefeislenco. The&c tvo bai:rbna flouriah 
In the praaaneo of oai-huliydrntti*, which thov 
diecompoM irith the liberal formation of niidf. »nd 
through thc^e aoida tlicv "limit intcfititml pufro 
factioii lUid infltirntv (fnvrrnhly) pntlio[o;£tc' pToo- 
r**c»i which arr rcn»cd or mBinlained by tbe 
eiiftin^ 'allraliDc fermentation*" (l{soh«Hch and 
Pfamiillfr). ThnL Ihc orpmisni^ in <]Ui»tion 
•ntojfoniM thr action of p[i(r>:faclivc bndcrta hn^ 
boon flhou'n in toft-tubc expenmenta (Hireohkr). 
Sinre thp time that v. Emmmrh upheld (h» 
colon badlluw (or n colon-1ik(< miwobel as thi 
r^ufc of Asintic (Cholera {^8^fl)^ opinion ii« lo tlio 
Iratht-'ueTiK- piiMrfTJ of tlie or-^ariifint han nnderp^uc 
many Huctuntioii!!, Following Koch'N dcrnouslra- 
tion of thp <v)mnifl hnHIhic n* tb*» *tiolo^ic fortor 
in chokra. the coIjii ba>'il)iip wa.*, to to My, ra- 
ircMVd a> a pntholojrir nirai^t, T,atcv. and cw])ori(ilh" 
Frsncp, gtrnt pignifir-anre wn« again atdiched to 
Et. The condition etill nhows a ^eat deal of chaoa, 
fllthousb, on neoount of mort* refined technio nnd 
llw eliiijinalii/ii nf uthor orgnifcipnuj, ns the dj«er 




Ittr Man, 

terr and p^ra^hoid btcilli tod BaciUus miertli' 
iU. frorn tho colon group proper, v« Ar«, perliapt, 
on Ute wijr lo A lUoTc tatiafadory uodcrvtaiLdiJig 
of tho pathojcODicity of thin ori^uttun. Altboo^ 
certain atttbore hold at the preunt time tbit ti>« 
cdoQ bacilli which nonuAlly iaboibit tho iDtc»- 
tintt arc <lcvotd of vinilrnc^^. etach a rftdkal posi- 
tion 19 npen to qu»tion, Anrulent «traiiig han 
oftea bt-cQ cricouutertd, hovercr. 

HnTnite»^ da th« c^olon bncillus appear* to be 
when confined in the intact intestiEiQAi it» viro- 
|f*[io*- rf>r niiiTiiulfl, iiUfioit^li low. Las Iwen demon- 
eitratcd in many inatancca. A boaillon culture of 
the avdrogo bncUlua v^iidi hua grown for from one 
to two rinys^ ami when freshly cnUiTntfid from Ihr 
fitooU, cjiuaca Uie death c( a 300 to 400 ^am 
(fuineu-pif: in two or three day», when givea mtra- 
|}critoti['All/ in a dose of from £ to 3 c.c, Subcu- 
tanccii« inoctilfltioDfl, the fer^iiiDg of culture*^ their 
iDlroductLon into tbn- bladder and biliary pa««tigv» 
induce Jatianimatory proccaflcs. It ie stated 
(Enchcfrioh) Omt whettior tlie culture* are intro- 
duced into the akiu^ pvntoueum or vcsftelB^ s/mp' 
torn a of HGvcrt ^jutrocntcritia are produced, not 
unlike AhaIIc chokmi. This fncl 4ioubLI<'8e in- 
But-ncnl V. Kinmerii-'li in cousidtruig the Qrpnnism 
at til9 ^%\it-^ of cholprn. Tho ^icrnl svinptomt s.t<> 
thoBO of an jicatr f^bnlc iElo^Io^tioa 

The oTi^auuRi ia most pnthcgenic wh«n freithH 
(■i)hivai*Kl, iinU soon loseg ite virulence after rv- 
pcfltcd tran«plniitationa, Aa in the cast^ of aome 
other bacteria, rirulenco may bo re-established bj 
"pjijuiij^?" through auitable nninials. 

The cultivotion of the colon bacillufi from the 
bloorl and orsiina of man qt mitrinAv hnn not the 



sigBificance which wae once atlscbod to it* It bdn 
hcta rwogniied limL llie colon bacillcw in parUcu- 
lar^ anil le^^ eumiTtonly other tDteetinal organisme 
uiuy eut«r the circuliiUuii a short tinit before death, 
at a timo wbcii refiislaQCO is ^or} low. and may 
obtaii] the getiemZ diBtrlbtition which i:^ »> oftvD 
encoiuitered at autopsy; this is the ao-called "ago- 
nal iiiTft£ior/' which may occur without much re- 
gflril In the jhriniary CHiise o/ iJi'aLh Tli^ i^ouili- 
tiona wliitb favor ogounl iiivaaiou remain, to n 
liirgc extent, ohicciirr^. Distiuct dofL>ets of the lq- 
tcstirifll mucosa prnbahly art ret efisrntial, al- 
thouijh thifl view hfl&its rt!prceciitativeif. In etutes 
of Itjw vitality in wbich resiataocr lo infection is 
dccicasc<t {disapiieaiance of complerac^ut). the or- 
j;j)Qi«m£ lincl cocditioiiji fuvorublc to proJif<;raliOD 
w!u*D tliey hnVG onrp mnche*! the eirciilalion. lit 
«pitc of the low Tirulmcij of tht colop Imcillus, it 
commonly has a etTtain amount of toxicity and it 
may oflen be of tignjflcflnr** pven ae an agonal in* 

rnst-morC«nn invasion of adjacant structures, as 
the gall hlaiJder and livtT thn>ugh the biliary paa- 
aa^cA, and of the peritoneum throusb the intcati^ 
nal wall, also oecura. 

It lias leun shown that thr ftilori bacinus ticcn" 
•ionnlly causes the following conditions : Snppura- 
tivu diolccystitis which mny oxlond to the livcT 
peritonitis, wpticcnua, meningitis, cyatitia, pyeli* 
tlfl and aseonding suppurative nephntie, and ub- 
<n*i«se.H in varioup orgJius, iiitludJng aiip^iurntivi? 
proci^ssca in the middio car. In one or more in- 
iCancN^ it has been tbotif^ht that it <!auaod vegeta- 
tive endocarditis. Prabflhl^ colon infection*! of the 
^1 bladder do not oocur in the nbaenec of biliary 




txytiVTios xsD iMMvsny. 

«taBU, Ordinarily csace of perltonitla In vhieh 
Iht <:u]on bncilliiK ik i-rtcniint«reil nlxo nhaw tbc 
presence of other pntho^nic orgoniime, u strcpto- 
co«i or Blfl[»)iylncorri ; tJiis i« alirajs ttie case ii> 
perforation peritontlU. DoubtlcM wronji concltt- 
Bione hnTff b««n drawn in many ir^tanoee nfi to the 
baeleriologv of perftoiiRiK Troni tlie t^i that the 
colon bacilhis rcndily OTfjgrows many other t>ac- 
Icria in culture me<lio. 
Cr««i<i> Kw'hf nrli nttrihtHe* gTPat importance to this or- 
^nnism 4a the cnujc of cystitis, cflpcciaUy tn chit- 
da>n. nnd i^tAlr^ thnl it i» probably the moNt lyini' 
nion oait^B nf ry^LJttA, pyelitis nnd ascending fup- 
purativc ncphritip. In lifty-oi^ht of m\y C110&4 Of 
cyMitU in children th^r rolon hrioillufl weui found 
eitlwr a1cu(^ or in nibi*d lultutes. An increased 
afU^lutinalmjr pnwer of the patient'* ticrum for the 
orgnni«mi( rnllivntnl from ib(- wnxw 14 not«d in 
1tie»L' caRtf, Datb mid otbi^ii^ liavi? described CSMB 
of urinary infrctionn due Xa H. futi diiforina from 
tbp ui^iial typ<? in that tbi> ^rn^-tli nn vnrinuE mmliji 
tE» le9» luxuriant and n^lk la not cou^lated. 

Pflvis hap found tbflt ihr »c»nmi of pntii-nt« with 
siiirh iiifectiiiiiK may be l<i^'t( irj ojifmnii* p<JrtCT and 
low in bftcli^riolytif. or nW ffwa, 
Dinrrhvu. Or«at int«r<ifit attftt^hiTA to tha ^lon bacfUiu In 
rtlatiou to enterocolitis and il^aenteric di^catCAp 
Eflclionch flpcakd of an tnUritis foUurularu, or 
efllitis <-iinit\(jw%ii, or coliiwlitiit, epidemi*^s of which 
hav(? been noltd at diPfertnt times, A number of 
tbeJie epidemics occurred before the identidcation 
of the djacntcrj V<aei]lii», and ceitain of them may 
have boon iruo dye^ntoric icf^tione. Neverthe- 
l€as. dyaenCery baeilti dn" tot found in all CHAe^ of 
f'Rterorolitia, and the probability that genuine 




cA»i» of colon i>n1critid occur can not as yni be neg- 

A ipeci^c cultjii lu\i[i litit uof bern obtaiut^cl^ 

inunumzation uiUi tltc <^hm baciilue coulee the 
formation rif hnrlmrirlnl arnlxv^ptors, opnoTiins 
and o^luUniitA. 

Not ftU straina of the colon biocillue are identical 
in Lhnr flpglntin^igpnio rt^iTptoT*, A serum wliich 
agglutinated one colon strain doee not nece^aanlt 
agglutinate aU strains. The reaction, occoiclfng to 
Paltauf and others, is largely au indmdual one. 
The svTutXi of n puticnt with a colon infection will 
;ig^'NtlinHlc Tlii? sUiilii vi\\\s\itg the ilisi^nMo, but may 
not oiloct otiicr atrajna- Honco, for diagnostic 
purposM, ilie test rauat be performed with the enl- 
ture vMch han been obtained from the patient. 
PfanndU»r isnyii in rcfercucp lo poliooliiia that if 
otbcr colon infection* oan be excIuJeJ, and if tlie 
scrum of tZie patient gi^'es lli<^ aj^glutination reac- 
tion in a dilution of 1 to TiO with tbf bacilluij 
vrhicli boa beat cultivated from Ihe atoola, coloo 
infcTtioD it indicated (Paltauf). 

Vnt'L^ine thtTujiy ]\ii* Ih'I'o i*ut'(.i'M fully apjjlud tii 
many of the^c colon bociilu* infoction». The 
auto^'cnouB oEgitri^iu should always be u»d owing 
to varintion in ihi^ tmrJIli. i-sjxrially in infiiclianai 
of iho uiiriar>^ tract. 



Tl. C1I0LK1U, 

In 1883 Koch diPOOveiNjd llio Vibrio fholtrtfi and 
oultivRted it from the stools nf HiolerH pati<*nU. 
The oruani^m may be ctdtiratcd from tlie bIooUi of 
the patients iuvariably. and is nover found in other 
diKOJiJiu nor in norniiil hIooU. except in the ease of 
non-suflccptibic pcraoiia who may be encountered 

nlto of the fwl ^^ it fto »ri a b <i is the ittte- 

ad 40* C A W7 vBpb nrthod of obuiniiig t]i« 
or giniw to ptiTv cnJtitrc fnnD fbc itoolf ««• di*- 
cmrtd by Kocfa. In Wb« «f ppptoo* booilkMi 
whieb lure bMi moeoUlcd witb th« fens cf t 
pttkiit, iht Tibrio proiifcntei rmpodlr and within 
s f«w hffnrs oxurt* in almost pure talture it Oi« 
lorfAM of Ibe litpiid. leolatcd colonics arc ol>* 



tained by trafiBferring a email amount of the eur- 
fttct^ lluiiJ to ItjboB of liqueQeJ geUtiii^ then plutmg 
tho latter. The colonics appear in a few lioure lU 
atnnll ImnsTdcent points from which pure j^nltiifFt 
ftrc made on a siiitabla mt'lium. For more positive 
iilentifif^ation flarghillQatifin teeta ftre performed 
tritli entictjolcra serum. The Eoyal I(iBLitx:te for 
Icf^tiou3 DisensL's (Berlin) keeps on harid a dried 
aeriim of known strengtli (1-10,000) for lliie pur- 
pOBC. Thff ti^ls being made wJtJi high dilutions, 
CiwigglutininB for other vibrioa are practicaltj' elim- 
inated. To the aggluliaatiou test may be ndded 
the "PfeilTef *ipehment." in whti^h the protefltivo 
|X"wpr of fln nnlicholcrsi scrum is ildrrmineil when 
^inea-piga are infected intraptntoncally with the 
suspected culture, If the eerum allows a protective 
power against this orgatiism which nppniiimales 
tiiat shown agoiiint a known cholera vibrio, or, if 
the organiems are dieeolved, the dia^oBia of chol- 
era JB jusiified. In performing such esperimente 
the semm is mixed with th^ ciillnre before injec- 

The rt^sifitanco of the cholera vibrio )£ very Jow. 
It di« in aboiJl two hoars when drM (Kcdi) anFl 
or this acoouut duet infection is thought not to 
occur. It \n killed intitrinlly by the boili&f; tem- 
peTatiire, and in five miauLes at 80* C It iw ex- 
tremely susceptible to carboHc acid (Jailed bj 1 
per cent in five minuiea), oorroelve Biihlimflte (1 
to 2,000,000 or 3,000,000 in from five to ten min- 
utes), and to ncidft, Cnloiiim chlorid ia an cHi- 
eient di^fnfiT-innt when thoroughly mixed with the 
fltcolfl- The micro-oTfaniam lives in distilled water 
not longer than twenty-fonr houra^ id ordinary 
wntcr for vereral dart to Nevera] weeks, and in one 



ivivcrrox AtsD juucsnr. 


ti»tatK« it vHs cuttivated from the vater of ui 
«qii«iiim after Mrveral inonUis. lu life ia abort in 
tlve pimtaci of putnfactira bdictcha and rapidly- 
gTOTiug atprophytes, (lying in hswct vmixa in from 
twenty-four to thirty hours (Koch). Bccnuac of 
ii\r hirgF otrrgrov'tb i>f Dthrr organiif;m74, tlie vibrio 
ctn nre^ bo cuJtivat^i from tlic «tcoIa Utcr than 
fron oiM to tlino dayi after deftth. lis life in and 
on foods depcnda on tho mction (alkaUaity U 
fftTorabI«)> and on the pretoacc or absoncc of 
moisture^ It li«v lojE^er in jktf-riiixiT() milk (tan 
daya) than in that vhich conloinA other inicroH>r- 

lofecttoit develops in tlift junill inCcAtiuns ful- 
towin;; ingcatioD of the ^r^AnUms. Infection by 
iray of iho lunga or UiroLigh wouud^ dooi not iakit 
place Id tlie pationl th« living vibrio occnn only 
in the iuteattn«s, and It ia c3ccn;tcd only with the 
l«c«a. So far aa known, it hh% no normal habitat 
otttndp t}ie t>oHy> alUioug^k a HtrrAin or otljcr water 
BU|iplir may contain the vibrio over i long period 
through conatant reinfoction of the water. Thia 
Clin only occur, dirot'tly or iuJirt'ctly, through the 
itoob of patiente. The wnshing of soiled Itucn or 
batinn^ in wat«r which it used for drinking and 
oth«r hovi^hold |ii]r|Kiiic^ liuve causeti QuibrealEB of 
Gbolcra. The water supply of o city may be in- 
ftfctocl by the discburg^g of pnTtentB who nn^ con- 
fint^l Eo iL ^lli|>- Couvalc&cctjlA mtiy retain virulent 
organmns in their stooU for fortv-eighl days 
(KollD)t nnd, nil Htntt^d, hraUhy pemoiih wlio are 
influtic«|>tible to cholera and who have r«aided in 
an infected diBtriet imy enrry vinih-nt vihnos in 
tlicir intealinea. ThcK conditions have contrib- 
ntttl to Iht fntiUtT nJiich, to a large degr**. haa 



met allempts to limit the extension of cholcni by 
t]UflrftTitine measorcs, Cholerft ettCTiris from ooun* 
trj- to couBtry along the lines of tra'^el- lu bome 
inslancee it ha.s bcoii possible io tnic?e Llic cri^n 
of wiJeapreaU epiikmicM lo [he Oelbi of (lie GHngt»r r:)!!**™!*! 
a region in which the disease is erKleniiCp Pilgrims 
frofn Tmiin i?arry the infsption to Me<TB, an<l pil- 
zrimn from Egypt carry it to tlieir nalire land on 
thajr return from Mecca. Either from %vpt. Of 
Uirough Arabia, Atia Hiimr and Suntheni Biinsia 
nr Turkey, cholera hae, with mofc or \&a rapidity, 
ftiteuded to Western Europe The development of 
mpiri tronait hflfi increftsej the rajiiditv with whicli 
cholera, may eitend. From Kuropo the diecaeo hOB 
bopTi carried to various ports of the western eonti- 
ticnl, Canada, the We^l liidJee and sotjthtrrii poits 
ijf the Uritod !Stnt<s, from which eaitcnfion has oc- 
curred i^ different flectionB. Of six xrideeprear^ 
epiilcmicB of lh(? (uwi one hiiii<ircil jeuf>, three 
hare mvolvwl tiii; Uatlcd StaL'^e, rvMduog con*id- 
^nblo proportions, Tlie m^anE oi in trod act ion is 
ritil nh\ny* Jiiipnrrnl. 

Aa in typhoid, t^ro Lypt^ of epidemics arc known, 
the two often tjcing DMociatcd: Firit, Uiat ^ana&d 
by water inf^vlion^ and, Mwond, thai, ir vhidi tbe 
disease tprtads by direct and indirect cotitJict. The 
eiploiiive character of an epidemic caused by in* 
rection of a water supply is much more etrikiDg 
than in tlic com of typhoid fever. Id Urge cillea 
hviuili'cdS) or thouannds, may he striken witbiji n 
day. The brief ircuh^ition period, from twelve to 
twenlj-four hour*, corlrihiiles to the ncutcncte of 
thfi outbreak. The diatribution of a "water- 
bome" epidemic oorre*ponde with the distribution 
of tho infit'tod water A rtmurkuUc o(?currenc*e il- 



¥llllr at 

liutrativg Uua point wba ttoM in th« opi^Iecaio 
whicli Attacked Uunburg in 189S, In certain 
strecU in vbich the roftidcnU of the two £icl«i oIh 
Uined their water eupply tiom t]if!«Tettt toaroOp 
OEO of vbich w:^i infect^, cholera uay limttod to 
that »ide which was stippljed with infected wat^. 
Onl^ irrcguUr eases due to contact iDfoctioa oo- 
oi]m?(] on the opposite side ^f the atreet. 

EpidcmJca which arc due «>lcljr to contact Mic- 
tion develop slowly aod irrcffularly, A commcui 
incident ii the succewitc involvement of ihe mem- 
ben of a fAtnily, whcTcne others in the imm^Jate 
ndghi^orhood are uiirtfTcded. Wnter-borne epi- 
dcmJcfl arc irvnrinbly compliMled by tho occur- 
rpnce of contact infwtion. Th? method* of coai' 
tact infection ore cot different from those men- 
tiouod uudur typhoid fever. Food or miU: which 
hfl* hcen iiifwlet! by contninirtntcd wflter or hj 
other mcanB may causo tJic development of Uolatod 
groups or cases. 

Animal* do not <:oiitract cholera under natural 
conditions. By rondering the gastric contents of 
guinoH-pigs alkaline and iotrorhiciug cuUureB into 
the irtoniucli through a tube, Koch induced a oboi* 
era-like pToctas from whi^^h MiP anifnals rlieJ with- 
ia from lwcDl>-four to thirtj-sii hoiire; nn intra* 
peritonea] injeetioD of opium, to quiet penstalgis, 
seemed to In? necussury for the mu-cess of thr rx- 
jjeninent. Similar results were obtained in vary 
youn^ rabbits by feedinjj cultures to them ([saaeff 
and Kolle; MetchnikoIT). Guirica-pigs wlihcIanJ 
the euh(*i]taneoi]a fnoculation af moderate aniount^r 
but are very susceptible to intraperitoneal inocula- 
tion. Jntravcnoxis injectiona are exceedingly toiic 
for rabbdtic. and a fatal chot^rn^lik? condition with 




locali^atiou of th« orgacifiinB in the Intesliiies and 
itiltetmal mucosa has been produced in thin wn_v 

The GBScntiiil poison of the cholera vibrio b In- Cfcj*<»mi», 
trnceltuJar, an*l becomes free only After aoluUon of 
the bacterial cclb. Cultures which are tilled care- 
fully as by cJjIoroform vapor (Pfeiffer) ore highly 
toxic, fltlboiigh Hip f!iii»l ftlone h non-loxii-. The 
flltrotea of young cultures fjave Ittle or no poison* 
oiu actlcn. The toxici^ of old&r Eiltrntea is dna 
partly to the solution of the bacteria with cooae- 
<|iient liberation of enriotoxiTi, and perhaps olao to 
flceomlary ilisirttepralion proiluots whioh hnvii a 
certain tnsicity. The aoluhla toiiii of Metchni- 
koff. HoTiv. and Tflurelli-Sulimbeni is a rijp«olved 
eurJiifoxin imd not e secretiou of the livlii^ cells, 
accoiding to IvoUe, 

Koch considers thot cholera is on acute mfuc- 
lioua process of the inleelinal epithelium, whereas 
iVip grni?rjil rnnrlirion jg nne of acute in(o;iiica Lion- 
It is assumed that the coudition in the int^fltincs 
eotrefipond* to that in the culture media, i, o,, that 
hoTc, too, no true soluble toiir, comparable with 
Ihat of diphtheria or tolnnua, is secreted, but that 
the toxin which eventually reaches the circulation 
ia that wliich u liberated from the bocterja aft^>r 
the latter have been dissolved ly the bnct«riolyain 
of thP plfljinta, fir perhfliin by the leucocytes. Doubt* 
less a great deal of endotoxin ia liberated in the in* 
teatinal canal, \yxxt it ig Kooh'u toneuption (cited 
by KoUe) that the primary intoxication come* 
from thoue orgaQisms whioh have pert^trated be- 
twLVD and ht-'neiith the (»pi|he]ia1 eellh and hi?re 
have undcriTrtno solution. One effect of th« toxiu 
in this situation it to caoi^ dcaquamation of the 

111 iho 


iyFEcnorr aho iJ/iiPXiry. 


nipid iihiOrptSon of iUe toiin from the mtositntl 
catiJii tohc« plncc^ tfirout:]! tlir ilcoiidcd «urf4c«. 
Thie th«oT} mppOMs Ibat ihe toxin is not rcndilj 
nbaorbei) Uirou^h tlie intact epitlielimii^ Thit liv* 
mjc vilno hSM never bun t^uUivAtod from tbc 

The cJkangcs in ihe intntirtee Jeperd oii the 
dunitJOD of i\\e infcclioo. In caiiox ^■hich prove 
Trtlnl wiiliiri n few htmn* thi* mniMtji HhovR nnly 
moiifrato Rcncrnl rRtitlcninj;, whicli is inicnetficil 
at tbi* bi>f\Jnr£ or Pewr'a putcHpa and the solitary 
follicice. Tho intestinal contcnte are of a mtlii^r 
dour fluid nature in which are auvpendM flakcn of 
muojH HM<1 qiithnlitim ; tbo flnitl mtiy he liDjfe^ 
with blood. With ri longer dnrdtion the titttrucli^c 
proccAfl«« in tho mixoen b^oino more iDtonse, And 
ooiinrst largely of iltfjifjiiumntJon of the iUpCTfrinl 
vpilhcliitm and intetiae too^&sUon of the denuded 
Fubmucrojca. In tho more prolonged ca»c«, ''ohol- 
om- typhoid," tlic mucosa, espooSnlly above the iloo* 
ewal valvu, mny show Olpltlhcrilic neL-FoaJ& The 
ftcrous surface of the inicfltincs it injixt&l, 

Tlie rational proplijlasis founded by Koch, on 
t kimwledjje of the biologic characteristics of the 
fommn Jindllua. Iia* proved of ^mni etljcieuey- 
Tlie ea^pntinl points nrr the following: 1. Imims 
diftte baoterjologic exami'iatioti of tho stools in 
«iitpiciOfi» <»ae«. S. Absolute isolation of paiient«, 
in & hospitdl whenever poniMe. 3, Thornugh cHs- 
icfcction of the rtoob, liiien^ room nud nil articles 
A'ilh wliidi ihp pirti(*nt hus luirn in i^oniaet, ineluJ' 
ing weter-^losete and privies. 4. Continued iao- 
IfttiOD during convalefloeDOe until the stools are 
free from vibrice. 5. Repeated hac(eriologic ejc- 



araiikation of the stools of those who hari? been in 
contact with cholera patients imti! their freedom 
from vibrios is asiureil- <i. Fn?qufjit txamirijilion 
of tJiO! wutcr supply at ditfuront points in or*Icr to 
ilctiv-t tim ((cciirreiiCL* of wiiter iutetioii 1. In 
eosc wflUr inft-ction cxista, excliision of the wator 
from all <!omp$1te ii»eflp and the imtitntion of 
means lo rid the water of infection. This mav be 
done m Ihe case of iDfcctecl wdle, but m the ca*e 
of lurge system* reponBiruclinn m»y be (lecessury 
for future protection. Water for household use 
Ahonld be boiEt^^l. Ko!le conpnree the crhndftiCDB 
\n flemiany ami Hitaaia during the epidemic of 
1802-4. In Germany, wheri* Koeh'a ]irinr?iplea of 
prophylajtifi ivcre rigidly r>bspri-ef1, about 10.(.iOO 
cnscft occurred, 'J,000 of which verc confincfl to 
Ilainburg, wh^roa^ in Hueeia, whore precautions 
were not **nfopettJ strietly or ^nendly, SfKj^OOO 
caaea developed during tbe same pcrioti- 

Protcctivc inocuktion has almwn itself to be of 
distiuet vilue for prophyUiti«- Ferron, o 3pan- 
iaid, fir&t practiced vaccinalloii on a large scale id 
18B4, although little de]ukit« kiiowlodK^^ of the 
Talne of the procedure reauUoil from his work 
Hr 16 srippDwrl In have tiMwl impure cullure*, JlalT- 
kiiie introduced protectire inoculation on a iaige 
«nle in InJia, and up to 1895 had inoeulated 40,* 
000 pi<mojL!f. FoUoning rusttur'a method with 
anthrax, he uffod two vaccinea. Vaccine 1 waa a 
culture which had been attetmated by j)rnh>nged 
growth at 39* Ch Vaccine 2. whidi waa adminia' 
torod fiTe diva hitcr, was n \iruleiit culture. The 
living organisma were UHcd in both vncirinps imd 
the injections were girca Aubcutancoiifly. Th< 
looil and g^^neral aymptoTna were mild- Instead 



ef lirtof; cuhum Kollc hu propeccd Iho tiM of 
TJnileat cultnrts vhkli h«TC bee» killed by npo- 
fnr« to M, UnpcntQiQ of 58* C for oo« honr. Th« 
vaoriiw ia pr¥«rrT«<il by tlie addition of 0-5 per 
ant pbokoL lu the J«pftDCBe epidaaic of 100$ 
this Bk4C)i'>i uu QMd on an exttnaiTtf •cal<^. Tlitf 
inddam of divc««e unong the uuinocuUtis] wu 
13 ptr cont^ ftukong tba i&o^4i«d O.Dti per coot ; 
the mortaljiv among t)ie oniDoculated mu 10 p«r 
rmt.. amoAg t^ iDOCuUt^ oaIt 0.02 per cent 
Hic dbcane, when it oeeomd in tho inoctiUt^ 
was of A mild type, A single injrcti>oTi of from % 
to A mp. of ft killed i£4r growth wae givcti mb- 
culaneouAly (ciied bf Kolle]. Strong Iim pro- 
poMd the UK of tb« prodacU of autolysis of the 
cbolcn vibrio te a Twoiiurtiag subatAiwc, t method 
fouRiled on tho obfurrmtioTia of N^mct and Shiga 
in rrUtion fo typhoid, and of Conradi otid Drig^- 
flki in rdatioo to d)'»eotory. The local and gmenl 
qrmptoflu ara «id to bo of a mild type. Th^ 
method hjw hod no pniutiiiuil trial. 

Ir^OKn what woa uid abcr« in coimectioa with 
Uic ao-^olicd chokra carri?t«, it is ovidcat that nOl 
aU aro equally miBcejitiUle lo iafection wJlh chol- 
era. In the few instances in whicli infection h&s 
boon attempted d«lib&ratoly> «omu conUocted the 
fliMuiH*, At It'ja^i oue vtt*t ending fAtpJly* vherctts in 
other* cither o niild ioffiction or none at nil look 
place. The conditions on wliirli siirfi cases of in* 
dividual irnrannity tlcpcml arc uot known conclu- 
fiTely, hlthong]) it i^ often intimated in a general 
wny tlint b tlroog bactericidal power of the body 
flviiflB. or A high phagocytic power on the part of 
leneocyles. ii rnponfiihle for it. The gnstric juice, 
on nccotint of JU acidity, ofTcr* a barrier to tl^c 




puasage of liviug viWlos Luto the fimall intcA- 
tines, and this is piLrticuIarly true of cholera. 
It ie neTcrtheless evident that the barrier in many 
ioBtaiiceA ifi not a t^rious one. A numt^er of cases 
aw recorded ia which mvestigfltora vhile working 
wilJi cultures hflFC become infected with cholera, 
the cases running typical couraea wbich aometimce 
ended fatally (PfdfTei, Pfuhl and othere). Or- 
ganiams which are iagceted with water may pass 
rapidly to the intoetinefi without being affeot^d by 
the acid of the stomach, or when fakca witli food 
they may be buried in the latter and hence not 
come in contact vitb t!ie gastric fiGcretion, II 
seems probable thnt the inteatinal opitlLcUtim Ijoe 
a certain rcGistnnec to invasion which is most mani- 
feat in the case of those who do not become in- 
fected in spite of the presence of the orgauisma in 
their intcsUnes. Natural jmmuuitv appears to be 
one which is directed ugamst the bacteria riitbcr 
than againet the emlotojiin, proliferation of the 
OTganifms in tiic intestinal epithelium being pre- 
vuritcil. Poorly uourished indindnalsj the very 
young and tlie very old are particularly auscepli' 
bkc Ol}ier gUfiLrointustinal difiorders^ in tho pres- 
ence of nn epidemic, preilispose to infection. Dfr 
f«ct8 in the intestinal opiihelium, or a decreased 
tcai stance of the lalter. inuy afford fnvornble 
trnditions for invasion. 

Active imiminity, as that which resulU from iu- Acqair«<i 
foctioD or from prol«ctive inoculation^ i% charac- 
teheed by the appearAnce of bactericidal ambocep- 
tont, opfioninu, o^tflntinini and specific precipitins 
in tl« MiuiEi. 

Amako find? tiiat opsonin, bacterid din and 
agglutinin develop with the eoarw of th« diMOK. 



Th^ IcD^ of tbo twgmtiTv phiM vartea with the 
a«T«Ht>- of Ui^ •>'mplrnniL Tho fulminiitif^ CUM 
htT^ 4 Bltort Mcntire phttM encUiii; m ArttXh- Thr 
tnHbodUo TCttch tlicir height dming coDra)»ceiuv, 

Tv moftt cuse^ Ibi- llin^ luililioiJjr rurvi-si run 
parallel, but thf bACteriolysiiu naajr b« mtich n^orr 
hj^lj dtn(op«d tlULC (hi* opfouin^. 

Arardiflg to rr^'itTcr und Mai-i, the untibiyliv* 
an pTodviocd id IIm blood-forming otkaiki. An 
ittacic of cholera coofera imiiunity of |»rolong«d 
duration, althoitgh it i« not nlway^ iib«>ltit«- 

PiMaTO iaimitQitT tp rrndily inducvd in nnimub 
b^ iajoctioa of mtnchcilcrm dcrum, Aa in otb^r 
iiutajicvt, it ifi of fthorl diiTatioiL Poiihtl^wi thn 
same conditioii tnay be indnnnl in mnti. Bcncilka 
hAf piTcpoMd tnixcd iinnrtnniE&liDu for prottHivfr 
Jnoonlation, utog IdDed bacteria wliicb bavc beoa 
>«tiiratcd with the !q)ecillc ambuceptors. 

Sciotlitiapj ba« been no more ftucceiflful in 
diok-ra than in tvplioid fever, Tlw antitoxic 
wnim of Ifntu Htid iiUirnt liu hjirl nn pmclftnl 
trial. According to Achard and Benwvde. the 
aenim of cholcrn pativnti, on tlio Ihird or fourth 
day of th-J div*flf^, n^lutiiintrt th*^ rbnlfrn vibrio. 
IToweircr, llicj u»td Ihe acrum in dilutions of 1-30, 
and in lhi« ttrcnuth even uorTual ImiDon feruni 
tnaj be sggktinnttng (I*fciiTor arid KoUe, cit^ bjr 
Paltauf)* ConTal<«ceat« tytn ttlwj flcACn monthn 
vA'S ehov an agglutinating* power of from 1/100 to 

TTie bncUtrmln^ic examination of the atoob la 
the most rcliublv nicana of early diagnofie (**« 

iisaiLVti i'saria. 


PUgne vai known in the setoml ami Uiinl ei>D- 
tiiric«. In the «ixth cciitur/ it rvvagcd the Jtoman 
empiro and d««tro}'od half the population in thG 
eastera provmci2fl. Under the iiaroe of Lht? 'Ijlack 
dcaUi" Jt iwopi o\i.'T J:;tirop« la 1317'5ii vith a 
sncriittfo af ont-fiiurth of Ihc inhabitants — alwut 
25,000,000, Ihirmg the fifteenth and sixteenth 
omitiinoe mntiy ^id<<miC8 pr&r^lod in vfirioua 
fiarJa of Emx^Jt, ni»l tin? iliai-ii^e sei-nied to have 
faatciicii il^tlf on tlint part of the \vorM. However, 
tho pn^nmonic form of the disniwi", thf mcist I'Oi;- 
tagiooa. graduall^y became 1cm Gonimon, or the vir- 
utonce of the infection '^imintshedr and this, with 
th(? inititulicin of (ju^nuiline rtgulntious, (leiTeoHmJ 
the prevalence of the plnji^ic diinrig and following 
the iaevi?ntk?^nt]i c^Tntiirj, Wvt>rt3i(.'l<>ss. there havt 
been cccaeional outbrcal«B in Eastern Europe since 
that time, Folbwmg tJn^ i-eeniiesconee of plague 
in Hfingkong jn IH^^ ami in othyr plaix^ Inter 
the dieoaae baa bcc& aiibjoctcd to acicntitic stiidy* 
Eti cause has been (3i>^07ered^ antl the importance 
of rigid c^uarautine moasmes eti scnporLti In pre- 
TcntinfT itfi univorci) «:?tension h:i3 boon provctl. 

In thft Honekoiis cpIdi»mio of lftO.1-4 ICiliwnl/J <:im»«*»eH«- 

and icr3m» working' mdepcudectly, diBcovcTcd tlic »tm»Biiiw. 
tacilluft of plague, fiadUvs ^i'Sth. The organiaio ij* 
minute (1.5 fo 1.76 by 0.5 to 0.7 micron*)^ luid 
typicallj i% of long ovn] «hapo. Ti)c frequent oc- 
ci:rTpnce of short oTal cellft (coccna form), longer 
rods and dUtortcd. awoilon, vacuolo>likc celts (in- 
solation or de^eneratioit forma) cignifivi: a high 
dfgna of plcomorphifm yrhkh is cliarartOTlatio, 
The lonjEicr tho diaeaae has lasted, or, on the other 
hanJ, llie older the culture, the more nnmrroitii art 



the Atrpicttl fonn». Jn bouilloc Jong cJiaiiu dt- 
vfilop. H U coa-iaQtUo, hafl uo HiigpIIa and form* 
no «pore& A c&ptiile tnajr b« itemonAtntcd by s[>* 
prcpnoto 1«cfa&ic. Jt dots not Etoizi by Ornrn'^ 
mothod, And nitZi rafrthylm? blutf, »rbol fochiiii, 
ctCt U3C cn<l« tUin move dmKly than tli« ceatrd 
[)Ohio« (p9Ur dainicg). BecauM of tie gcnonl 
propertin it a pUoed in & group iriUi it tminber of 
bacterU vbicJi cauM bcmorrluipc eiff>ticcmud in 
miouft animnls— tl)« liemorrhftgla s^]tto«mii 

There occtt» in bouiUoa the m-callod eUiJactitG 
groiffth. in which vitlbla prooeasea extend froin tbg 
nnfaco toward the bottom, where thry meet other! 
proc«Mac which extend toward thd mirfaoo "elAlA|;-i 
miW). Tlieee foxtnatiDCS utUiin? u!* Iht-ir starting 
poiDta the side of the fiuk or drops of buHcr or 
oil wfaxth art placod on the sttrfacc. CerUIn otbtr^ 
orguiEaiQfl gmw In a similar muimt;. It in iajj' 
to be A diamctariittic fontur? of the plA^c bacilli 
that many lovolutioTi formfl appear cm aj^r wltich 
contaioa 3 per cent, of todium chlorid. The opti- 
mum tomperatnro for growth w from W* to 39' 
r,, which i> somewTiflt lower t)T»ii tlmt for mo»l 
pithOfCfiic «]ipini5ri5. U fcrowa mtlicr »IowIy even 
under the beat conditioiu. In mixod cnlturoB it » 
mwiipviwii by lapropliytit: orgaiii^iiiii (». g^, rolon 

Tho plaguo baciUQS may live for from four lo 
tv«ii«Bn#^ wTon da)'9 m tho putrefying orgnn» of man or niii* 
oiik. lU Tirulnice may be retained in the cadaver 
of a Tflt for two monthia [Bandi and StA^iltn* 
BalittTori). During thia time the organiama peno- 
Ualo all tho tiMuea of the body, even grovtng 
IlifiMiih the akiD< It may \iv» in Iht pua of a 



bubo f«T Iwwity day* wheu iinmiied witli other 
orBtniimi (Albredit and Ghon) ; iu tlic ^puluni 
from plnguc pncuniauiA for U-n Ua^a^ itt viiriou5 
f^d9> as milk, potntoM, for one to tlircc vceks; in 
watf^r frnm five to lueotv dnys, dffppnding on r.lie 
nambcr of eapropiotca wbicL are preeent; m earth 
irom two ft-eeks to throe uwelUls, d&pendizig ou the 
ijuantity of organic mAttfr uiid otijer orgniiismt^ 
In all Ujcso instances tiie higher the tcmpernture, 
i, fc, nhovB 30" C, and the morp nnmpTOVs (ho 
saprophytic orgfinisnie, the shorter id the life of 
ihe plague tmcilluf. In vinler, vhi^n coutomiaat- 
mg sflprophjlr's grun less rapuHj", the plnguo bRcil- 
lu£ live* loDgv^r. Ita rceietnnco to dceiccatiou, eun- 
liglrl sinl disinfpTfing ng^U is rather low, par^ 
ticntlflrlr when the eurroundins temperature ia 
nhore ."^O* C In temperatupoi ^f frnm 29" to III' 
C-, when thorouh^ly rlrirtl, it rmrl} IJve* lunger 
thin from n\ to eeven days, i^horoaa at lownr tcm* 
pLTJitiirpt, Ifi* to £0* C, cnlt[in>9 may be ohlained 
after from one to ser^ral weclns deptmdiiig on the 
nuteriat ^^hicli containa tlic orj^amsms. It livea 
longer in wonlcn and cotton threaila (clotliing) 
thai) wlu-u isolated ju in dutft; hence, ilubt infection 
is iniprobahio (Dicxidonn6}. In flpnium (pla^iie 
pnc?i]mcnifl) anfi pnnileni ^jcndAtpi in which thi* 
bacilli become iccniBteil to a degree, life may per- 
sist for from thrco to four wcokn, Snnlight Hlla 
ihem in fioiii two to six lionro, dfpendin^ on the 
tempetntcre and the proximity of the OTganisma to 
the Burfaoe, AUh>>uf»h culturoa for llie purpose of 
taecination have bwn kiil«l at a (pmperAtnre of 
€5* C. for one liour, precautions to icsure an eres 
diatribotion of the heat fire noccuory to render c«r- 
lain Ilu» doath of all oi:gfliii«m«^ A li^mpi-'ratun? ot 

A5» SMMCXm. 
B««n.o4tt* Ca horn tm 

tfapT«m Ittnlif- 

their rim- 
faft IB a mo) tefc; 

r. Ttw 

™ tfUtt odtw tW' 


GalMt6 cartnct cnlhm« 

llsti fbna tbt wIC 

tW M^l 

te Ink «l<Mri Ve^j. He 
fn^Ml of tbe ov^Qftnian 
U tW Airf tMoe cMirtihift, rfaimn^ at tf)c «BiBe 
^m wnmmm of a mttmm aMoA of ai4id)lr J 

TW ylfm tedltai is cnvedta^T virtiknt for 
ntN t fi i mfc. gtfiw]^ wi matAttt : fo«i«Hiat 
b« tinil«il to Mko tti adolt nUuts ; titim ml- 
vaK foK Aog^ «viB«^ tmn, bgnw, •fawp, pat>. 
war br nfKtni artifldaUy. tltlmu^ thtj ootti- 
noolj rcroT^T hva afte lu^ doMi. GoiiMa-;>tjr« 
aad nt> nav b* lufn-ted bjr ciiWittaiMnB«, iatrapvri- 



of infoctcd material or by plncin); H on thi; iiEiaml 
niucoiu inenibrane 3V in the coajuncttval ear. jiinf by 
uUialatJon ezpcrimenU, (h« bat m«tUod coaunooly 
reaultiug in plagut; pnoumouiu, Uuinea-pi^ and 
vtjiing I'ahliiEH rile of pingui? sc^jjLici'initi in rcom 
Jour to five days when culturra or motenal con- 
Uining the organismB (spuliiin^ fece^, orgace Trom 
pia^fae cases), trc jubbi-d iulo Lb> ahuvuo or eveu 
unahaven ekin (Aibretht nnd Ghon). This expcii- 
ment is of value for (letecdng rinilmt plague ba- 
cilli and aeparating theiu from couttimiuiiting or- 
g&mtum. Following inociilatioa ialo % eutan«oiu 
or mucoLiK Kitrfm'c* n local ruarfion of varying tu- 
kiȣity develops in which tbo eubcutan^ue tissue 
becomes eilematoua or even h^irorrbagic, in a num- 
ber of houm the Tegional lymph gknds become 
Bffolleii Binl ht-rnorrhaffic, and io fi'Oin two l« fivt? 
days thp jinimuls die of pTa^jiiu srplic<3mifl. Cul- 
lurM of low vinilcnce not infrequently cause a 
chronic infeoUoo which is charactQmed hy tlio tcr- 
iiiufiou iif lar^ir ^runiilomsitoiiM ncnlulut on thy Eur- 
f*cc of the liTcr and epieen nnd in the omentum. 
Such foci contaui many plague bacilli, and Uie 
d^ath of Urn nnimcl resiihs in a few weeks from 
intoxication or from goncra] inflection. Although 
rubbitifi arc much lass aiieccptibic than TUla or 
gnini*a-pig», young animals succuinb to ciitaowiu* 

Dieudonni cit«« four foe! In vhlch plague h 
knmtn to l>i! fimlcnnc at l)ir pr<<Mrn( timr: One h 
in China {province of YiSjinan), from which the 
Hc-ngkorg epidemic onginaled; d second in the 
HicialAyaA. which W to tho outbrcaJc in Bombay; 
a third in a moiuitainous region aonth of McoCQi 
and a fonhit was found by Koili and i^upit/ji in 



Ibi* mmA 

BriiiA Bm Alric* WAr \\\t murre of Uie Wlitte 

aurily t rtiawiti of the rtt and thit ccrlntD regnon^ 
iiiiii Mit4AfMlia b«citiAe of thL« faa. n«t«, in 
tcrtslft otiirictB, nfe' from b cfarotik form of (be 
■ H w n ^ iDd it b poflBible thtt the oix>nism ot 
tbMW anpum fnrrcaiMl virulpnoo. ■« d mnift^* 
^MBtt of vfckii 1Ij« infrcti^n brcni:ir« nii1f4pr<:td 
■b4 rtpidir ftui ajoomj; tbaie Aninul?, It it 
h di Bwd thftt tnuiKaiiivkiD rnun rit trt ntt mny 
onrv IKrM&xh Um ntiag of plafiM cndaTeTtf. 

flMft pkpM-rtrickrn rub «ilT iaf#c< lofltthy ntr, 
^iaQ»-pV« iod tnrwkrv^ t>v biting them. Ttif 
«tiric ftf tlH* luditn PltfTue Commisfiton d«moQ* 
litntcd tWt Ihf n<(Ml mf!ARi of tnnnnimion froqa 
rtt 1» Tut tiki fTttn rat to man \% hr mCAnn f>f 
flMLc. yttnVn^, vhk4i arr rfwlilv iiifi><'1ivT if |va1 
in tkt tttb» nocB vitit infix^cd ratv, remain woH 
if pT» to <<»J frMD ^^K It ha« been r^p^t^y 
dvwkafrtntrd th^t flm* fnr^iv nil» nml Kinirrrl* 
»iU ffi^l *^r man. 

)h i'^Ufiimta. ^aiml< infMed vilb fiUjpi^ arc 
an important founv i>f infrrtini> in sinn, Tnin»- 
ninm from tat* \t ^qninvb ictf fron m^hitt^Ip 
to nrti by ni«aii* nf fltJie bit h«<en d«monMrat«d by 
Mi-Co^. mwl MrT*"!*' anl Wbrrrr report * ra»^ f>f 
trftnftltii->ai<«n f^>Tn ^qviirr^lp fn man, protitbJy 

Fliea. ai( upU a^ Heik^, mai dbtributo \)w httcillt 
fr^m rata ^r Ib^ inf^^'tM rxrrrtion* **? nian 

Whnu ]>lnjrv« bvft3e» a near rimnlrv it coinmoiilj^ 
ni«Vtf4 its flr*t nfpramnr^ tn MMut ritW, Pr«- 

TXAh'SAttssioy or plaque. 



mmably this is accompliihcd throrgh infected rata 
which may bojird n ship flnring ita stay in a peat- 
ri-lcien liarbur, anfj wtiif^li «ub»eque:itljr escape at 
the new port. 

EpHi^micf of plagiip lack tin* ejfplcwivti-lilw Bud» KpMe™!*** 
dances in tbcir development which charactcrUf* 
cholera and, to a certain eiten:. t^-phoid and dy&- 
entcry. Tlic cu£e& ocrriir ifi groujiTr uiu) in jmrticti* • 
lar houBea m such n inoDiter that direct and indi- 
root oontACt Kocm to h« largaly rf^^pncsibU for 
traufliiii«sioij. Ev^ry epidemic c»f plague may be 
divided nito throe Eitagua: a alow progr^ei^ioE from 
ginall centf?rfi. sn acme of wiVl(*preBd death, and A 
alow rpcTitsiiMi (Dirudoiirn'O- It seeni* probahla 
that the diacaac apreaiJa rapidly and extensively 
only when the poeiimoDic form prevails, 

III man. infection takw place throufc'h the ftkin 
moat fK^uentiy, although the mncoiut mL^mbraao* 
of the mouthy iioso, pharyox, tousile or the con- 
junctiva art poMible iufoclioo atria. Often no 
loed wactidn is produced, and the point of en- 
trance may be indirntcd only in a jprneral way by 
the swollen lyrnph ^lamis of tbn rcjcion. Icfro- 
quently a pustule or small pjjrb^uirle mark* the 
point of entraQCO. Primary plagitc pneumonia is 
caused by th*? inhalation of pogt-kdun trifltf^rial, 
partii'ulni'Iy Tine pa.rtiflea of spiUum from a pu*"u- 
monic cnac, and pcrhapa also by the tnhaliilion of 
infected duat; Iln? hil*or i* proh/ibK of !t*si impor- 
tance bt^irauac of the abort life of the organiam Id 
dtist- Ki-rii in 'jrdiniin' fepefikui^ inrriuEo dropa of 
fialitu ure llinivvii iiiltj Uii- aiir. InfiM-Hnn in tJioHght 
not to occur throngb the stomach or intcatiuee. 
In the pneumonic and a$ptLc«niic forms, tho in- 
fected uiiDC and fecea contribute to titc d]£Eseniina< 

isyscTiox A^D iMuvstrr. 


Hon of the organi<iB&. Compart sitb pn^xmioaic 
Aail ivpUcmiic pla^ve \ht hvbtm'ic form i« much 
Iwfi duigorott* to • commQDity. 

FDUowj&g eataDeoQt infectha Ui« regionftl 
\ymfh glands become ewolkn and heraordiagu^ 
mod aDder|p> more or itm extennre nocrooia. When 
Uw mffctioQ GStflndi be>«n<! th« lymph glands tho 
Uood Esijr conbUD aiornaovt qiiantitif^zt of hftcilli 
(pli^e ■cplittmia], and tho Bame cooditioD fol- 
lows plflfM pofonutots ; m Uie ereni of general in- 
fection doatli foUoiiv In H few liuuni. "Suouitdsrj 
potiuQooia" and also '^secondaij bnboco^' develop 
a< a ooQsvqveiioo of blood mfoGtion. FTcmorrhagto 
into the miiooue mccnbraDe (eapeciaily the stcon- 
ach or 000010)1 eDdothetialaortocos ((Hrii^anlium), 
sail vmriocn putnchjrnatous orgacu^ mih E^jdrtmit; 
de^poBcratJoa of tbe latter (tivcr, kidocjs and 
licart), are cfaancteriftic nnstomio diai^gea, Tfae 
Mphm is ttsuallj awojicu. The toxic aubalaDoe 
etulf^tly hts, afinititt for many lissocs. 

Muod tnfrrtiaci vUh Uil- .iinrpUKxicciiA in not 
aiKomtiHtD ai^d » a Mrioua complication > 

Tho following are important poinu for proithy- 
laiis: 1. Kjkrly diugnoav as »taljlU]]Uil h\ boc- 
teri^oCM exftnitDStioti of blooii, ^jiutum, and !luid 
takvn from a bubo ^ilher br a fe}TiT:pi or ttttcr in- 
cifioa ; d, in like tboroafEli JAobtion of pancnta and 
of those vbo bata boen espoced ia iDf«cCJon; 3» 
In tha duinfoction of Mt^rpUoag, of clothing and of 
infected bonete, ^hich in »ome iostancca maj 
moan tbe dertmction of tho latter; 4, In the do* 
ttnKtlQO of rats; G, propliylactic injections. Up 
to tho prosent Umn Iho most ^octire moasnro of 
getting rid of rat» i» to oiTcr a bounty for eadi 
antmal ought. n» practiocd in Mnniln. In Cnli- 



fomii, the work of cxIcriQination of aquiireU, mLi 
and fleaa boa beon earn*<l on o,vttniiiv*Iy by th& 
U. S. PtAiIir TIc-Jiltti ami MArtitC'FloflioUl SpitW. 

The vaccine of Hallkine lia* been uacd eiton- ^'•««<»«' 
lively in Ibe^Ejl The Imlifln plague eommiiiaJon 
found thnt tho inddenre of iliKefise ftntl Uit mcir^ 
laJity were lowpr omonp ihe mocuUUrl Uian the 
uninfiniluU^I, nlUjfuigli many of the inociiffttcii 
COfilraclt'J Ihc liiflc^iee in a heiiign foniK Tbu vuc- 
clnc conHists of bouillon cuUurea vbich have groini 
for sic w^lca with slnlnctite formntion (see nbdve), 
tbm Jdllel by (rxpoeiire In ft torn prat tire of 05" C. 
lor oHe hour; from 0^5 to 3,5 c.c. are mjoclod, nc- 
cording to tlit ngf* End sbe of the indWidunl. One 
or more siibsoquent injccliocis maj be given. The 
locfil UDd gfliLorjil r^Actinre arc of niotierAt^' ^cvot- 
ity. Protect joii lecciiies manifest only wveml 
days after tbe lUDcuUtion and mov por^ttBt for 
maajr wogks or montba. TIig vai^j'infl rccfimmi-nded 
by Uie QermuL couiiuiHuoii codsjsU of tiro dnyar 
old agar oulturde which have b^eo kill^^ by heat 
(65" C. faroniT btmr). Lus^Ug anil GHltotli uhlist 
Iho toxic prccipitntc dea^ribrd above aa a vncdnc, 
Terni and Bandi inoculate rabhite or guinea-pigK 
ijDtnLperitODeaJly viih the plague liadllufi and 
after or just preceding tleatU collect tlie peritonsal 
txndjili?, it) wh'u'h the or^ani^ms urv jillnwtHl |j> ]>rf>- 
lifoTfttc stiil further for twelve hour*. The bacilli 
are then killed at a low tcrmperalure, and IhU 
fluid, after nn addilioo of n prw^Tvalivc, coimti- 
twteo their viitt'ino. Althou^^H tbc liwt Ihroc vac- 
ciiiefi bnvr pmvfld of vnlup in aninml rxppHTnnntS^ 
thcj have not aa yet been used eaitensively in man. 

Bttredka and Sht^a rwommetid the ua« of mixed 
•etirs md pnuive immunWtton, ns migge^tcd in 


israi^Tius jkSD t^yvMTY, 

ttiad^o to tjphold and choler*. in thla fiuUuee 
niUurftU^ winu pln^uf^ bncilli (kilM) nnd anCi- 
pUigtw 9«ruui. &h];-& rcport«d ^ood rt«ulU by tbf 
use 'of l}>c <<oinbiii«d iiiHhod in iW epidemic ia 

The iroicuQitT which it prckdue*^ br protccfirc 
tnocnlfttion. Hlct* tbflt which Mlom nalurni inftv- 
tiODr 19 coaeider^ to bo ontibactcTial Inasinuch to 
UWMrum icqairv* ioc^r^scd 1iai?t«n^idal power for 
thp hnrHItu^ hut dintn: nn ability in tmitrnMr^ iU 
toxic couftiluonU. Tlii^ iaduencc of opeomns it 
ciiienUd for cxpcntnNUal phn^^lotit, and ic nn 
Lni|>oi-tnnt fflrUr in t1ip ine^hanisin nf imTnuntly. 
Antjplapue Benim contfiinfl nlw comidcment'dyTi- 
ation nntibodie* ond |irwipltin>. The immunitr 
wtficlt follows infection i^ of long duratioiL 

I'rophyloctic injections of fiotiploptc «cnim pn>- 
duc* a temporary immunity of about two vceka', 
durntion. TIk* Pjitilt^ur Irredihitt- prcp«r«5 i\vc' 
fonim of VrrBin by immnniwnff horece first with 
killed and then with living oallTir*^. The inimvn- 
iialiOB ii dtlfmlt and fri^m iu:rcTal montli* to a 
yoor nod a hnlf oto roquirod for the productjon ol, 
a stronfl: Berarii. Wli^^n ibe blood is drawn its 
dcm from tivini; pla^uo bacilli nnd from toxic tiib- 
cUnffiB murt he ai^nrod. The iinmnm^ing raliw of 
the tei'uiii IB detciaiiiunl bv llmt <]uaiiliLj whldi 
will eavo a raou»c from a falsi <}<^ of \xvine plftfni« 
badlH^ the Ki^nim bt^tnj; givrn ?■* hmire in Bdvnncft 
of the cuttiiTC. TliiB is ficcomjilieliod by 0,1 to COS 
G.c, depending: on the ftr«n;^h of tho aorum. It> 
mratm {Hiw^r U Htrnnkd tnuu thnt qnflntily, A 
to 0»1 ChCh. ^bich aa'cs n mon^c when admiiijj'tcrc^ 
IS hour* nftcr tho injection of od f)th<>rwi*c fatal 
dosp of culhir? F*>r prot*c(iTft infJcnUtion in man 



from 10 to 20 c,c. aro rwommon<lftil. uml for niir±» 
tive purpoflCB from 30 to 50 c,c. Conceming the 
Tulue of IhJH ^eruin Dieuiloufi^ cundud^ an fol- 
loi^a: ''On the hnsli of the resitUa obtained in 
m&D and in snimfll cnperimenls wo can attribute 
no positi** curntive value to t\\v Purisiuii serum, 
aitlioiiglj a certam infltience on the coura« of th« 
disc^fie can not be denied. On the other hiindj the 
B<T»Tm IB suitable fop protective icoculfltioc wlien 
immeiliat€ immimity i& necessary, tit foi ihoac vsho 
aw caring for caecs of plague pneumoniu. tiuicc, 
however, the prelection aflortied by this meana per- 
iisU only for o few daya, subsequent active immuo- 
tzation nith killed cultures is mdicatvd m hoou w 
poitible for those personfi wlio are e^^poaed to in- 
fpctioa for some time." Tlie fnvoruble ra*iilt» 
noted l»y a miiaber of observers ^vould seem to jua- 
tify further use of the serum for ciirnlivc pur- 

The serum of Tuvel, preparetl at the lii«titLit« 
of Bern, 19, like that of Yersin, bact^icidal and 
agglutinating. Antitojtic as wdl aa baotcricidal 
proporties are t-laimeii for the serura of Lii«tt^ 
which 15 prepum] ly tEnmuni^fttiou with the toxic 
precipitate mentioned above. It baa been naed ex- 
Icnnvcly in Ihe Ireatment of plu^ie and in a num» 
ber of anitdl epidemics favorable Ihnu^h not thor* 
ougLly convincing reaulta were reported. The 
urum of Mnrkl, vhich ia «iLppo«cd to bo Aatitoxic, 
hu h*d no pratrJical trial. It U ppepureil by im* 
miinization with old cultures wliieh have been 
loUcd by chbroform, 

Aceordiii;; to KoUe ntid Krnmhciu antipla^ue 
ttmin sliould he tt^lt-d us lo (^km'i.'n1riitLi>n of hII of 


/yrnrr/ojr lyo tuMuxiTr 

the vsrmi motibodtct in onkr to obtAin b mrrerl 
ide« of il* tilno, 

^I'ri^ Altliott^ Uit Boram of pstiwU acquirtt a ett- 
Uin B^otiBBtinf povrrr, it U rather loir (1/3 or 
1/5), «m1 does Dot become mAiiifcit until during 
Di* MC0ii4 v««fc of tkft dtsM«0. Before thu time 
-diognoib bjr cUnii-al or locCeHelo^ mi-git« ran b« 
m4de with c^rumij; beocc, for cUitica] diafncvu 
tbt mdion IiBj tittle tnloc On the other liBiift, 
A •troQg BrU£fIal agglntinaliiig •enuu obtaia«l 
bjr (Ji^ «q)edflc unmunilittOD of aiiimBlf b of greal 
tbIik for tht idcDtifir«tiOD of titc pbjni« bcicillai 
when eoltuMd hat^ bo<>n obtainod from ffupect^^ 
naiMMi Artiflrial f#TumH mjiv ngj^ntiiuitr in <1[lo* 
faoiu of from 1/JOOO to 1/€6(W. 

kn^wMf^f on this point U dafid^nt. 



Prom the mldnilpJiiil of uifMioii tuvt] immuuity 
juilhrax i% of poilJcuUr iDlenst Ik i* the fint 
(li^Asc uf wfiicli tite bacterid ctiolo^ wa« pror^ 
401! m whcdi the ap«Gl6c micnbe wu nW m part 
C4iTtiii« for th^ producticn of irlil^dnl imtpiinity 

Anthrax i* pfLrikuUHy a (Ijmbac of cttttc ADd 
ibccp. tiul it promiU in c^^rtdJn European couH' 
trira, fopfdalljr HvanV in AuKlraJifi and in Smith 
Aiii«n<«. It does not Oi!c-ur cjilenKivrly in tbb 
oon&tJj. Definite TcidonB oro at times boaTilj ia* 
f4Cltd, antl i1 it iix vuch locditiea that Um diMaao 
|k inojt frfq»cDtI]r trajisniilte) to man. 




A« cnrly n% 1K50 liAjcr and Dc^nint:, olffO I'ol- 
l«nd«r, had rli»ic-OT«r«d the prn«ence of email rode 
anil fSIaiueiiU iu the blooJ uf niumats uliich had 
died of anthrax, and the work of Koc^h, Padeur 
and othpra flm>n cnljihHtTied thitt this rod, the an* 
Uiiaa bacilliiA, ia tlie cauae of anthrax. The diBcor* 
cnr of Kooh that Iho hnd!lna forms cxtrcmclv rc- 
eiatant spores, eiplaineil the persi^fern^e with wliirfi 
the diacaju? infccU particular localities 

The flcthrax hooillus ia a fairly large organiem. »p»r««. 
tK niiT-«ha|»il, non-inolile and growK with irharac- 
tcristic appearances on Taiioii* cnltnrc media. 
With Uie proper temperntoro and ciilnire meditim, 
nitd in till* ptrwnry nf frcn fJi^gi'n, ibc fcirmalJOO 
of eporc« begins after about twenty-fonr honra of 
growth. Their eiJohitioa ia eoitiplete in from one 
to two t!ay», and evcntunlly the of the 
colU dif.intQgrate« and tho spon^ aro aet froa. 
Sporea are not formed in iliB body of an infected 
animal- Spore formation h not e^M^ntial, hov* 
aver, for the continued life of ih^ crganiKm; at 
high iauperaiurcH (43° C), mid in tin- ifrteenci? 
of minute amounfa of acids and nlkaUs or of car- 
boHi? acid, Ftruin* may be so altered that they Ioec 
permanently the ability In product? ^porea. ITiLder 
fjkvoroble eondilione the sporos germinate eom- 
pl^twly in from thrpe-fjunrtarfl to lae and onp-hnlf 
houra (Orcthe) by a process in which tliey loae 
their refractiTo appcaronoo and Aeaumo firet an 
oval and th'-n a rod shape, Tn the body a caphule 
surrounds the bacillus, iind it groins singly or in 
\"ery abort chnina; in eulturo media it is rery diffi- 
calt to obtain e^piinlm. The long threads which 
appear in eulturo media, eapeeially bouillon, are 
not found in infected «nimaU- 

tJiFBCTioy ivo fUMVMrr. 


Tt§ bMilhi ilaalf Aovi no lutuaal reoifUac^ 
mn mon nvistuit than IhoM of anj 
btcknam. Wben drird on a 
hftT« b«cft kavra to Htc for fro«a ten 
1» t«dM jMtft. ConoMna enblimsip (l-SOOO) 
iafDftj nuttitai <Fnieokd).ind dii^^ 
itt «faoot 100 WoTf (Monosit). Bafillut 
d. iUpfajlooocd ADd the b«* 
«f yrta^hiiHit ftn atid to uta^nise ita 
fovnd tbat the dried B. pndi- 
dw nnileoa of ilie or|;tDiam for 
tlic twct were injected* 
n« iMtatt teallai ii nnuafaiblo for itc infec« 
tiOMMn. A tiwilj iiiilliniilfi of a loop of a nru- 
ha/t orilV* vill «nat a fal&l iDfecti>oii in mie«. 

^. A^ilankourfBC<kB&»j bep«^iKtd b/ fccd- 
il^ the iftfm «r taMii^ aaimah to inhalt them. 
IW «Minc j^c* is aUv tft kill the bacilli, but aot 
III* ^aMik vUek (trwuMtt after thor reach tho 

TW «imi>B n dbtrilntrd b^ the cicniioQi 
vhT ttwMJ aiMl^ and aim tMr death Oie ad- 
}«.^m« intt liCDMW tenlf inlnfed bj the dia- 
<<Wrf«« «hk^ «Mf« fns the inleetiiMa and bUd* 
M U tkiia AtvatiaB tlw tedlti pan into th« 
«|\vi«V *AiVK ^ vUch thfT nmaln lublu nnd 
itr«)«ftt hx a laaif tiaiL 

lh9 UfMiOtt ftT baida umdlj ia ■eanpliiAiad 
k> tk^ ii^fflriton i^ a|ianB vhidi hAT« bf«n dlstrit^ 
vtv4 in tKia «^T. the aporaa germinating, B« de- 
«-nbnl aKin^ after Hmj h«va rvadhed the Intaa- 
tlMk Tha diiaaaa M^y ba primarr in the aim i 
Hwfciwnaf awitijMat putnla. In man malignaitl 
pttaluW u iHr oontmoneat type of inhctloou oetiir> 

AS nuns. 


ring cffpcf^iHlIy sition^ ihoae nlio liaVQ to do witli 
cattle and sheep. The bacilli^ however, nmy gain 
ftntrauce through tho lungs as m the so-callod 
"wool-sijrLerV itiaeHse, which is raused by the in- 
halatioa of infecteii dust from the raw materiah 

TIte general i:wt! million insll animnls ie rapid- 
ly ffllnl (one to Ihree day?), ami Ihe occurrent^e of 
dcflU^ is Bornctim*^ so ;ndden ns to be c«!I&i npo- 
pleeliform; ia mac the mortality ia about 50 per 
cent. Malignaat puatnle runs n more favorable 

Tiie general infectious an? marked bj pvinptonw -i^xtB, 
of intertflc intoxicfiUon and acute degencralivc 
chaf]g«fi arv produced m the paronohymatoiie oi- 
gatl^. Massive numbers of the IjuciUi are round ia 
the blood. Neither a soluble toxin nor fin endo- 
toxin characteristio for the organism has been dem- 
onutrnlml up t? Uk» present time (Sobernlieiin). 
although there ia abundant clinieal and unatotnio 
erldeoce of inteuse intoxioation, The productio:i 
of mechanical injuriCA by the large masses of ba- 
cilli in the circulation ie doubtful. 

Rational prophylaxis involvea tlie proper disjW' rropiiitoiin. 
ni of the bodies of animals wliieh have died of 
fluthroj, the exelnsion of animal* from field* 
known to be iufei^teJ, suitable diBiuft<c(ion of atallB, 
and finally protective inocuiction against the dia- 
oese^ No part of the anthrax cadaver Ehould b« 
Qsed for comniercial purpoa^e, hecauBe of the dim- 
gcrof infwliug tliOEe who work with the raw ma* 
l^rinls, ClfanliufSH and Ihe ii^ual preeaiitJj»ns 
n^inat contagious diaeasea should be observed by 
thmc who artf tJcpDsod lo infection, Ijcoring in mind 
that the diseaw (iii*>' be tranamiftcd by way of the 
unffs and ahmftilury tract, m well as by the skin. 

4 DO 

v.^*■rcT/oy avd axuvMrr. 


It is pmbdbio UiAt nc <li«um is more poq>J«xlDg 
fruT[i The aUndpoiDl of immanilT than snUiruc- 
Thc TunaticiDf in £UK<ptibiIit> osd inunuDilj 
among ilifTcrrnt niiiitiulii Arv exlr^iie: Ouinva* 
pi^n. inLlJU aud mice are prababl; more •ujiccptj- 
Ue tbnn vhccp niid eattlc ; comparod vith theee ili« 
(log nnd mi *ri- rolntiii?]_v iinirion^, whtirtM* finrls 
!Lud culd-bloodcd animaU c^n be infected with dif- 
licully. Altboufh the microbe ia rcadilr killecl by 
■LuiUblcHtTLinu (rnUiit, (*_ g.), >hUc1i itn cJ5-l*L ui nut 
no index of in^mimity. Tbo aeriim of the hif^ly 
raiceplJbk' rjibbil U eirongly becteriHdjtl in t(^- 
glao cjijieriTiifiLlA, wbtrtfit» Dtat t)f the mon rcttUt- 
ftDt dog, or pftt, hne Ijttlo or no bn(^tcrjcidftl power. 
B«€anae of tliis i neon 4] intent relation^iip of t1>e 
flerum to immunity, and &iaoe tbe lG[icoc>-ti» Have 
n high phjii^ocytic poorer for th^* anthrax bfloilluj, 
t'tni^clikvj Prank find (»theT>i agree wJU: Meti:)^]- 
kolT tn fl^i^'iiia^- vaii^tions in ticc nuttirdl immup- 
ity iif iliffKnint rmimnU to vntifltion* in pitB^ 
cylic power. Bail and Fctlcrsaon, in citenaiTe cx- 
perimi^ntal work, di*ccrt'erod coiiditioiia which, they 
bciic\c, explain ihe lack of correspondence between 
serum properlJea arid natural imninnity. In Wie 
Bunini [jf tht' n.'lntivc:!y immiii^c dog and chickon 
l}i?y found bactcrlcidaj an^lioceptorf but no com- 
ploment; heuoc, the eeniin could «how no buoteri' 
ridnl NtttiiHi In tliti ti«t^g1iiKK^ Tf, liuwi^vi^r, limt^h- 
cytea from the eacie animala were ad<Jed to the 
fl^rum^ the latter became bactoriddoJ, It may be 
aBsam«d that in the rniirw of infi-clion the Amho- 
ceptora are activated by eoTtipIement wiiich ia d;a- 
ehurged from the lettcocyte^. I'hc failure of the 
bactmcidnl siibstancea of the rabbit** aerum to 
protect the fuiimal naa ascribed to the ability nf 



the liwtiw to obwrb tho Amboceptore (Sob^m- 
heim). Their work is of suffiei^nt imprriUincD to 
dcinund rvpttilioji, 

Wright fins ahow^Q the importance of the opBonJns 
far pIiagot-vLottist of \hv. mitlinis hidllus. 

Hccovcry from epontanwiie infection ia eaid lo 
coDfcr & degree of immunitv, wMch, however, ifl 

Artificja) immunity xiwiy Le produced br active vitwiaativu. 
or pfte«ive iiamuniziitioa. The Bret fittcmpts at 
v»"?i[ihUo31 wun^ mmlr in 18S0 by Toussnlnl., wlio 
injix'ttd Um: blimd oT infccli^d nninials nflcr it litiJ 
l)een bi-uled to 55 dci^reca for ten minuttis. The 
bacilli were tbu^ ottenujite^, but thoy v^ta able tn 
form spores gnbapqiipntly anfl Taeclnatirm was nnt 
aWfljB 8iJCCC«fuL Fafteur ufcd two ^accin^a. Vac- 
cine I connmLcti of a culture: which waa attcnuntud 
by jjrowth at 48* C.^ nnd which contninvd no 
Mporen. Vacciiie II wus a virulent culture, iind was 
inJecW in from tea to fourteen days nft[;r vac- 
oina I, ltd uae IS eoid to liare cauncd a dccreaee 
in antbrox in heavily Infected di«trict«. w1ih a con- 
Mquent decrense of the disease in rnnn. VuriQn« 
modifications of the voccinra of Pasteur hove been 
devieeJ by othera., and tbcy *oem lo be ttniiilly laie- 
eeuful. In some ingtanccK killed bacilli and tho 
[inxluclft of tjHcterial growlli liave beefi iLHvd wiih 
Icfs success, The Anikr^diclmtnunproimliiv of 
V. Emmerich nnd Lcwa U not of ostnbiinbed valne. 

Immunir Bi'mm for IhprHppiitio purposes Is pre- »"*iip"»pr 
pared by immnnii^ntion, first with killed or atten- iiui«< 
(iAti<d (^iilttirrK iiTid thpn with vinikrt strains Th^ 
tvti vticciiicj^ cf Pjwteiir may be used, Although 
the flemm has been shown to hate fairly iitron;: 


ittnoTtos -ivfl syMuynr. 

■ proi^tive pow^r«, it is ot ]vm r&ine vihtm umd for 

H curativu purpo^ei. It proiluc:« no effect after 

^^ bJood fitrcattt hiu bircn inv&dsd hy tho b&eiUi. II 

H grvatwt vaIuc is for the pn>tnrtian of h«r'U wh«n 

auUinu liad declATfld itMlf. In roan H hu becD. 
utvd chicly in the trtttnicnt nf nmlignant ptututi' 
IB which the prognosis, even witfiout specific treat*' 
mcnt, \& not unfavorablo. The beet kDowQ acnims 
■Tu thoso of Setavo, prvpAn^d from thv goat nnd 
of MfodtTi anij Deuiecb. The propcrtieA od wtiich^ 
the value of tli« AoramB depcndA &re unkoown, Sch 
iHEnihi^im EK wty ponitivo iu sCnUtig that Uu? hui^* 
tcricidal power of an animal'B s^rnm i« not in- 
croaeed by innnunisattoo or iDfeotion, and the €X- 
iHlt^icr uf an niililoxiit in not r<-[<rif^ii]/iHl, Ai^ in 
tome other in«tancca iminuiLizniioD mny caujc an 
increAAC In opsoBius which would render the s^um 
effecLiTe by lit powi-r to cau>c incruiM^d jibAgocj- 
^Pm»4 >m- Tlie method of Sobeml^elm, ihai tif m\xvi] ;i;.-lt\'« 
MAntBii" a^id pa»ivc immunix&tton, ictniif to be BucctHssM 
as a propbylaotic m^^^ire. Tho vaccina conaista 
nf 4 inixtEu^ tit aiitinenim ard bacilli. iTniuunc 
and even normAl ecrum« nt times may agglntinfite 
the antbrrix badllua^ but the reaction i« iDConstontj 
anil iht! iibilily at mi immune serum 1^ canw- ag- 
glntinatioQ 10 dc indcv of itt protectivo power. Ag*- 
glntUiation U ecm^what difliciilt of det^rminatioii' 
b^AUK nf the tcntldicy of the lAcilluA to grow ia< 
tbc form of chains. 



Mnlta, Moditcrrant^an or unduUnt fcTO^diecovprv^^ 
in tlie Island fif Mnlta, hIho r>CCTirg amon^' British 
troopa at Qibraltar, and casea have been dinovered 



in tbe Caribbean Sen, Porto ]\'u:o, in HougVon^, 
Hamld. and in India. Historically, it has been 
traced to tbe b^nniDg ol (\\€ ntreteenth oontury, 
h\it it WAS first (li>«crib^d se an independent ^is^ftse 
hy Marfiten in 1059, It is sdid to be ejitending. 
The diBcaae aauiilly ruoa a long coiirse, whi^'h la 
souiewbat tvpboidal in cbaiacter, and tli«re mny be 
one or more relapse. Tlie spleen ia f>nlarg«d. but 
tlie intt&tincs ore not ioTohed. 

"II ja distinguisbc^d from typtioid b}? its long du- 
ration, sometimes extending over many months; 
by n ranrac of fever c.ihibiliog marked unduin* 
tione; by tbe oceurroQce of copiou? pcrapirntions ; 
bj the fr^q^ient appearance of rbruinatiL^ articular 
disorders as well oi b> neuralgia and infiamirAtion 
of the scrotum and epididymis" (Scheube). It 
occur* oapooislly in tbi> suranier monllis. The 
incubalioii period is about Cfteen dayfc. 

Biiaset- Smith foupd tbe eeruiu in practically all 
fltflgea of the diK^ase nnd in oonvaleseeoce to ha\o 
UUle or no baclpriddal powEr for (he eorcus, Nor- 
mal serom appeared to be more bactericidal than 
that of tbe patiecte, although eucb ati aetion was 
often niiHeed in normal aemm. Wrigbt aays that 
normal human ennim ia devoid of bactericido] 
poTcr for the orf^aDJani. Baaeet-Smith also con- 
cludf^I that the pbngocyti^^ jiower of the pntient'a 
leuooc>tt.'^ lA losA than in tlie case of Dormol leuco- 
cytes. According to Wrigbt, the organiam "ia om- 
inrntly Hpnsible to the opinnit^ nrtion of the nor* 
mal senjm,'' under tbe iurtuence of which it is 
taken up in large cumbers by the leucocyte?, 

Agglntiuatidn by the aeruma of patients takes 
place in dilutions varying from 1-300 to 1-2000 


or m€D AC higU a* 1-6000. Agglmisins develop 
Uix\y earijr in Uie oeiAne «t the iofection, «ad (he 
tect ia of gntH diagniMtic io^iiortance. Thcv di^- 
*pp«r ia about two jean after nc^tvrj (Birt jukI 

BseiUttt mtlihrtas, disoorvr^d by Brace (ISST) 
in the iip]«m of patiaiU who had AM of ibe flis- 
0i»^ ia 4 miaute 0Tfaniain» alightly oral io ahapc- 
According to Oi>rdoti, it poetPSiec ocw ftigBlluin, 
tareJv Inu or foiuv and m tiligliUjr tiioUle. TIm 
bacillub is fctuid in pure cuUureo in the fipl^en, 
wh&di ia ^rc^iljf tiiilai;^, lla gitiwtl) in culture 
media U ytry ilow. 

It is thought that infect1^1 water niAy be oiw 
meaaa of tnaaniiasiou uf tliL- iliaejue. Lalwratm^r 
iafcctioitft nith pure ciilhirc« hate ocoinod 
through sniaU uoande r9«\ihlDg in typical at 
of Malta fever (Birt and I^tnh), The diaeaae ia 
not tranRnittpd from person to person. 

Up to the preH^ct time ih« nio^nkey Itt th« odIt 
aninul known with Mitfcrptibiiit)- 1^ artificial jnfro 
boii> although the orgacuria faas a tertain rini- 
lenc-e for rabbits and gtijiiea-pluft mi uiLraperito- 
nonl or iniraorrebTnt injection {Diirhftml. 

One attack confers immunity, which may disap- 
peiir, liowiTVur, fifli-r mmv Lime (Htigltee). 

Ad immune aerum which waa prepared by 
Wright ifi aaH to inflnecce fsTonblj^ the conrae c4 
the disease. 


onovp nr. 

Acut« infectioufi <]]««fl«ee m which acquired im- 
uiuuity of ;)n>l(>:]g(!il duration U nut ufUibluliiii), 
[n eotao in^tancca soluble tcxinc axu produced 
whieJi art' of unkoown imporlfltioo \n iho infections 
(•tapbylococcua, ^trtplococcuei). Some of the or- 
^ni];tn« contaio rather strong <mdoloxiQ« (pneu- 
motoccusy gcDococcvfl), wh«reaK id olliers a r<>a«oii- 
Mt lpQii« for their infectionmcH U not At hond^ 
In som« inetancf^ inimiinizatinn cai]«o« tncrcAS«d 
r««ijitaiioe 1u inf«4.-tii>ti (>^t»pli_vlueoocu«^ 4trepti>i^>c- 
Ciu), vhcTeui tlu« property htis not biYD fully 
dfmonctrflt^ in olhona,* The i->runit nf iirmiin- 
kcd AoiirmU mu^ or iimy not be proUctive for 
oilier animnlc. Those orgnni^rns which caiiao ayt- 
temic infwtion give ih» in leiicccytooi* C^^<"ppt 
iiii1u«nEfl). XjDcal mAamiitiition^ arc accompanM 
bj the ncciimulfltion of polymorph onockar IpiunV' 

I. ysnuMOcocous tsr^cxEONd— ^mkituosta. 

}fo onft orgnniam tn the fflCDliniTC c4ii*o of nnj 
one type of pncnmonin, excrpt perhaps tlie vinuw 
of «yphilifl and tuWrt'ulosiB. Any mierobo ^-hich 
duiM-a pnmitn'mia run nliin nrt tip inHimmatioiu 
in oU^ci oTc:an0. Tito following may cauae acute 

L TktB polpt !■ i3l|II<Qlt uf a«i«rni1[uUou whoa ut orgifr- 
kn til* tittiv nr Dv [rBEtLuflrnlfllj fir BntmalH ^loCnmt, 

Pbr onion la. 


tM'KvTios -ivo lUMtynr. 

pulmonitU: Dipl^tocc%t$ pneumontiF, Sireptocov* 
ctu pyog4rtst, SiaphjflacocetfS pn^gtum, bftcillue of 
Fhetiloiidcr {B. pnitimonia)^ B, infiumum, B, p$8- 
tit, B. diphiheriiP, B. ttfphosus, B, coH commttnit^ 
B. ivbeicuhiis &i\i\ M'\rroctiitnt oiiarrh^Us^ Tlte 
flipjnianifl of lubtfrculoiift, actinomycoaii, sxphiba 
find *c»me otbor infrrtfon* ratiio clirniiii* inllnmmn- 
fioDs of the lunfTs. Some of tlic»Q or^niuu* hire 
nTready boeD coniidercd and othora will be dl»- 
i^itwfTl lntL-r, ill (hpir i-rtlnhoii lu yiinnTmrniU, wit)»- 
fiut, howoTcr, cnforiQfl; into dctflih ox to Ihr vftrioiis 
Dipi.ti^ikpcu* ivpes of tho disesii^. The Diphrfimit pn^nmoMit^ 
a Uit conimonvbt cnxtw of lubnr pncum^vniji- H 
produoca lobular pncumnnm not infrc^jiic-ntlv, nod 
)i«- Ik^ti f'lnud no lhi» only orpmiarn in ftcutv 
iriU-i"*tiliaI (uiciimoniii (Weichwlbnum). 

Fmdliinder (1p*S2S fonnd that cnpFHiatod cooci 
were present eon^faitl^y in llie ciudate of pneumo- 
nia. Sncli <HKd in aII prob&bilit;^ rcpreoenUd the 
organism which fit prpsent in known fi» the pneo- 
* mucoccu*t yut the cuJttuea whidi be oblaiiied eome* 

what later shoved the chainctcrUti&i of the orjcan* 
hm now ktiown At. thv bnrilliiiA of Fnedltlnder. 
Fiwenkel, in 1S84, obtain*?'! Ihtf fir&t-namcd coccus 
in puTo culture, jxiicl hiM invcatigationt, togotbsr 
niUi tboAo '>r Wpii'biirlbsnTn nni) n^any othf7«, 
eventually «*tobliah0d tho independence of th« 
two 0Tfiiiai*ini. 

Tb^ typiefll pneuinococciis ia Blightly elongnUd, 
and both in t>ic tisiucit And in culture media it 
grou'R in pAirj;^ Typically, ftleo, the pair po£se&tcs 
a tflpaule which ia prfseut cocstaiUly in the liesucs 
ami may be obUiuerl ou certain culture media 
(inilk and Mnim). Tf is non-molili*, nonoflngir!* 
7nt«Lfoinisn<>pporf«and atatcflbyGram'a method. 

Typtntl anil 



Bfithoi' eennt growtli occurs on the ordinary 
cuUurE media in the form of amall colonies which 
wficmblG thoae of the streptococcUBj and ualcss spe- 
ciat inerilia are n=erl it nsnally car not be carrie*! 
tbToagli many generationa. When grovrn in apu* 
turn, or on o medium which c<»QULn8 ascitic fluid, 
thf blood or bt^rum of man or some favorable aiii- 
mul, ata virulence may be preserved for some time. 
Bj growth at ^9^ C. vimienee is lost rapidly. 
Stratna which are atypical in one of several wnyA 
are caoQunterecl, Thcj m&y show low virulence, 
may grow well at ordinary tcmporatiirefl (the typi* 
cal organiem not doirtg ao), may produce long 
chains in liquid Tucdia, or may grow without a 

HeceBtly tie danger of confusing the pneumo- 
eoccut with the fttr^ptococont has receivt-d renewed 
Attention, and newer mcthoila of differential ion 
rondcr it estromely probable that such confusion 
ho^ occurred in the pitEt. An imporlanl differen- 
tial method is that of cultivation on agar plates 
which ContaiD blofjd (i^tholtmiillrr and Kr.3tno^v) ; 
Iht* '(trppto(!<ioruw prndnr*"*: a rlmr zone of homo- 
lyzed coq^niclefi about iU colouiea, wlii-reas ihc 
tiolonica of the putumoooceui pn?scnt a ^ii-i?eni;h 
color nml prodim' nc* hi'irolyKi=. Tii nsing thi« 
t«( fi. F. Kucdiger found a surprising number of 
pDenrnc^occi in nonnnl thronfa^ wheron* prcivio'w 
work had ■hnwa theni in he Ipap pomnmn than 

In spite of the poor \iabiltty of the* orifiniam on 
ordiD&ry culture media, it is fairly resi»taot to 
6eejcofttion and «ualrp;ht, wpeeinlly when cmboddeJ 
iii*f)utnin- It ispoodhlothnt the Mirmiinding ^pii- 
tom is protective and that Ui*^ ve]!-fonncd capsnTtf 



tsnoriojr avd tMuvhiir. 


which the COCCUS powegoi as t parasite, in ctcojcs ite 
itaiilftDOft. When drieil and powdered I'c ia mui^ 
teas Mdatant, baiiig kilUd bj direct eunUght in 
about an hour. Like othe^ iiict^ria, it r««ieu 
diJTuw Bunli^t b«tUT than tfiirct, and iu chr 
farmer nuy liv« fnr sh lon^ n« :>!> dnve in ■ dric^ 
pute (Bordonf>ITffr^]uKKi. cited bv U'oichael- 
baum). It baa very little icnAtnaco to h^t, hcing 
killfd by A t«mpOTatuie of 42* C. for ten mmutot 
Ko dumrtiTriittin NoIubV toxin hft^bsm obtained^ 
although more or Jc«s poivoaouf ttibvUiaccft, some 
of them of A diemkal nature, hate b«en dcacnbcd. 
Pre»timnh!v ili^ toric prt>pprtj>« reside in an mdo- 
toxiB' The pixE-iimritiixin nf F. nuil G- Klcmpercx 
wa» prepared by prtcipitatioD n-ith alcohoL Th« 
pneuiDOcocGiu it ft py^ffenio or^aiusia and cauMd 
exudates vhic^b are rich In HbHn. OcoaaionaHj 
Hf-roua Tflfhvr Uiaii purut^nt eiuJales are pri>lucefl, 
Iu toxic adioQ is directed to'^Ard various orgait«, 
and it is douMfcl if itny of th« tissues of the l<Of)y 
are noTi-Kii>u'i*pf[bIi.-, Somr stmini Mrt* Kupponxl to 
be more neurotoxic tlien otbera. 

Tha euACoplibililj of aatmaU varioa grMtly. 
Kalbiu and mice are 9xtr^iHy euscoptibl^ and are 
xiA^i\ Sid Iful. nniinnlii fi^r th^ ii^rntificiitiim of tHn 
orjfnnijiiD. OtliE^r Uboratory arnmaU have greater 
lUfistQuao, and tlic pif^n and chiaken arc almrMt 
absolntety immune. In Bnacoptiblc unimMi a rap- 
idly fftlal cocccniia or more or logs eiteD«iv« It 
lesions ore produced, depending on the vimleacc 
the culturo, the aeat of inoonlation nnd the sosoep- 
tlbility of ^« snimfil, Tn Tabbits lobar preumonla 
has been produced by inoi^nlation into the pleura, 
trac)ica» blood ^tivam or submitanwius tisauR. 




BoMBov and otben kaTe elicpvi] that Tinilcat TirBi«Kqv> 
p&etDOCocvi an much lea vusocptibte to ph«go- 
cjrlom tlvn an noo-virvleiit rttviw. 

By anlol^ the mbifanct oa vbich the dod- 
nue^pCibUilj of rinikDt ponuDooocei to phago- 
cjto«i« flrp«»il^ rait be rcnoovvd and id tkifi mao* 
□cr nruldt pmrtimococci reodettd readily phai^o- 
cytabie. Furthcnnonv bv Irvatiiig flTirulrat 

Btrtiju of offganisnia witlt the autoljrtic prodnclfl 
o( Yinknt OfsaEumf, the reodUy phngocytable 
DDn-Ttmlent pfwvnococri ran bo renderai] lees 
tmceptible to phafocj1<fiu. Thb mbstiAoe* vbich 
ein be extracted from piMaiiio«4ed and oo which 
thn i«&istflnc» Li> phAjpx^rtmlH dffMtid^, Roeef)i>v 
has called ^nraliD/* Viiolm neuta Wling for 
two minuti^ ind is ifitolublc in aleobol ntid etli«r. 

The pnetimooocmu i§ prenmt in tlic uo»c» moutli <iM*Brf*iH>a 
and pharyDX of & Urge pcrccDtflgo of iDdjridaaU. '" **" »•*/- 
It i» ent^ouiil^n^ loore frequently in crowded cities 
than Mi country dv^tricts. It persists for weeks 
aod TDODths in the moutha of contaleac^ts from 
pneumutiiii. uiid i( rtnt^bia liie moulhs of tliu^e 
who arc tn tbc ricinity of pncuntonics. It is found 
frequently in the coujnikctiTfi and ocf^nfliooAUy in 
the deeper air paaiafea. TImt it may reacb the 
ftonaaeJi and iDteatinea with the »;TLitum is appar- 
ent, and it haa be«n found thcrp as the t^ause of 
diphtheric ecteriti^, a cocditioQ which may be 
flowed by pncameeoooii* pcritonitJi or general 

Thc lunj^:^ are infected by tnbahtron of the laairHim 
cocei. Saspeoded in dropletf of *nli\"n or mucua, '""* *"■■•*■ 
or adherent to foreign particle*, they may be ca^ 
nod fairly deeply into the bronehial tuboe- T!iQt 
Ihev ever reaeJi Uie alveali Ur thia menna nlori* Sm 

t\rf-vrm\ tf(D tMucxirr 

«%■ tmt*r- 

quMMNiad hy nnaiiv, Twd facton vrouJd •eoia to 
I^KtcDt tbeir bciag carried to the alveoli bj cnr- 
TvnU of hifpirod air: Finite foreigrt bodi«« Of fo- 
trcU^ dropleu are likely tD strike ani] adljvrv in 
Uw vilUb of the neptntory paasage* before thvf 
have UaimvJ a gtta.1 lengtli^ and from this Bvtoii* 
tion Kunr ajcain be carried out bj tbo action of the 
ciliated fpi^elium or ootghing; tti« lOTtuotia paa- 
ngvo of Ibe dohv anJ iCn h«:n> auO mnlut KurfAcm 
arroil iubj Bucro-oncaiittnii^ Second^ the Tdodlj 
of th« iii*pf«d air is grefttlir n>dkx^ or it n*7 hy 
th« time tlie partiolea might bare mdi^il Die 
alTooli, a oood&tioQ vhicb mKlecB tbvr arreet all 
tlie ROTO profaftUo. Nvrerthdoaft, pneumororr) do 
reach the alTooli, and bj aone it ia suppooed thet 
flTan ID health thoj' are carried there more or Uei 
conalantlv «uJ are u consUatlj deetroyed. Occa* 
Siontlly thcT htrt Wn fouiKl in the parencliTma- 
tona tiasuf of tl;# luugs of iiidlvidtiflU who hare 
dinl of othi'r tlian pneunwconcuii infit^inru i>r of 
non -infectious diteaece. In ord«r to shoir that 
fnicTO-orj^r)l0ni3 may b« carried into the paren- 
rhpni bv iir^piration XeQiiinger alJoired anioiala 
to iobaJe a 9pTo>- contfiiDin^ Micr^coctmt prcdtgio- 
tuM, end kUISnn; the ajiEmsU after one-half hour* 
vaa able to ailtiTttc th« cocma from the baae of 
the lungs vhore only alveoli and the flaeet broo- 
chtBl bTaiiclieN were preeait (eit«1 by WeichwU 

VjinouJ other agencies liAte been euggeited bjr 
i^liiVh the cfxvi tnuj be carritfd to the parenchjina- 
[ous tiMuc. For example, duri&fr the forced rce- 
pjrAtoTT efTort« which acoompany couching ikey 
may be carried from i\\e bronchial branchea into 
the alTeoli. Or the or^ntsnA having reached the 



bnsuU, nuy be carried through ih& walU of tb« 
liiiiier, pcrhapff by- the ieucocyt?s, anri reach tiie 
iLlveoIi directly througti the lymph ohamiols or 
afler having cnusej infectioD in the peribronchial 
lymph glands. Others erpress the opinion thnt 
pneumonia foll*>ws blood infection in inanv or 
most iiiHtaiJcee, t, o., that the infeotioTi is lieiiiulo- 
gcnous, the cocci haring renched the blood in fiome 
obscure manner. That the infection tjwy te h^m- 
atoj^enoufi i^ shown by the rK't'^fiiuiisl ofi^inrt-nci- of 
pncumoniu socomiary to pncumococcus infection in 
o[h<?r parts of the boriy. 

Knoi^-ing the fairly confitant presence of pncu- c-naotit^am 
mncoocL in the upper rcapiratoi^' pnasafcs m the 
nnrmal inflivlduah it »i»^» cErtnijj that some un- 
ubuaI condition must arise to precipitate infection 
of the pulmonary tissue. Concerning the nature 
of tliEVP conditions, we have littTe but theories. 
They may rest cither wjth the microbe or the in- 
diTiduo), or with botli. The pmjumococci which 
are normally on the mucoiia surfaces nay nndcr^ 
wi iccfeaeo in virulence, or more virulent o^^•an- 
icmn from the outer wortd, or from pneumonic pn- 
tienl«, may be inhaled. The latter condition ia an 
imporlanl one in relation to the oonta^iouKue^ of 
pnuiimoEUH nnd the development of GpiJemic»- 
Tark and Williama found n larger perccntoge of 
virulent orgaiiiam* in the apntum of pneumonici 
than in thnt of normiil pt^ntonr. Tt i» [fiiKAlhli? thnt 
the pnctimccoccus in bein^paaaed from one patient 
U> another undergoes an fncreate in virulence^ lim- 
ilai to the ircrcBsc which mivy br obtained by paw- 
llg bacteria through animaU. 

On the ot^l'^ hand, it is vrry probahU that t»» 
flential changca take place is the IndiTidual. 


ixi'i'crioy AKD /jrupA'irr. 

chat^gr» whii^h in Muni; may ctUNe lJ)i: lovuivi) xc* 
aifitauce which n ao often rcfcmd lo «a ■ c^mlltJOD 
for iofoGLioa. Exposuitj lo oold Itaa long bwn 
krjtivn u iui imp<>rCuiL ptedispooirtg £tictor, al- 
ihougli wo ooatinuc in ij^orancc of iti prcciM 
efl^Cta. Aftiinals an? mon? (iiK-q>tib1e to poetinui- 
cocGuji infection After artificial rcducliou ot iht 
bod> tompenturc it U poaitiblG that a Iowcm! 
hotly temperature may decrease antibacterial at^ 
tivilica; that the activity of the bactericidal fer- 
menU of Ibo plaamn or of the leucoc}'te8 rtiMy be 
ffUpprrKBurti, or phjigcwjtoeia m«y be inhibited ao 
that orgarisma nhicli roach tbo bronchi and peri- 
broiidikl lymphatic fttnictar«« aie allowed to pro* 
lifcratc It i$ probable that in health the Icqco- 
cytofl contmiiou«ly paae through the broaciua] and 
flIveoUr walU ^vliere lliev may tuglohe ferei^jn par- 
tideft (conl duttt) or bucterm, aad Jcucocytce an 
present nn tbq* murmtfi membrano of the mouth 
cavity. Following' cipoaiire and the reduction of 
the body tcmpvruturcr o^ foUowtnjc the prr>[on£ed 
inApiratien of vnld air, the nelivity of the phajr"- 
qrtea may be inbibited ao thai cocci which rmch 
theac fiuiidccx are uot irif;eHted and continue to 
proUfatmtep or Ihc mwe conditiena may decrease 
tbfi ezndatiou of the leucocytes from the rewela. 
It i« posiible abo that Lhe activity of tho ctUatcd 
epitholnim is rcdticed nmilarty ao that the coed 
are not m rcaihly c^rriod to tho exterior. 
oi!i*iP Kxtrerae exposure ia not alvayit followed by 
vm"nri ]mi-untoma, however^ nnil rot nil cn^n; of pi^rumo- 
nia arc preceded by exposure; many other condi- 
tions may pre^liapcae to irfectloc. aa a love-red 
TwtManee duo to alcnholisni, other infection* or to 
non-infcetioiia proeeeaes. That eertaln local con- 




dUions ma; f^vor infection :4 indicEUcii by the fro- 
qu^ncj with wliich irnliviihinls with cbroiiio luber- 
culooifl of the \\m^ die of pncumocdccias paeumo- 
nio, md tliB dovclopmODt of the dieeaec in ar«as 
of liyposl-st-ic Lougpsl.ifin. A^q ie of iiilliMrdrft. "To 
tbc sixth year the prcdispCBition to pDcumoriia \$ 
marked: it dimmisbes to the fiftceotli year, but 
then for eacli *ubBU£^iiciit, ilccnili? it incrnitcfl" 
(Osier). The cause of these variationa is not 
known, although the rise in later year* may le 
a*5onatc<l with increased exposure. 

The conditions which prcdigpo^ to infcolion are 
now the eiihject of fti?tivt> etudy in tnimy hiUorft' 
torica^ and the commission which the New YorJf 
Ucpartmcnt of Health eatabii^hcd for the study of 
nculo reNplratorr dit^toiov madf? imporlnnt ob«crra< 
tiww a* tfi (hi- ppcvt!fi-ia*i? aiul virnli-nrp rf pfifuino- 


H^ny ohflorTCw have found ppcutiiococoi in the Cftrnwli- 
blood ID a large percentage oi the fast**, and ixxtut 
work ljy Itonrnoff itidirntr^ thiit thi- hlood i* prob- 
ablj infected in all ai&^i at tome tttngc of tlw dU' 
cane. Tbia beic^ the coae, tbe frequency with which 
pneumococcTta infectiong ocour in other orgHtjs lu 
complicfltions of pni^um^nia h readiTy understnod. 
Pieuritia ifi preffcnt almost eonstantiy, pciicnrditie 
frcqucnlly, nnd the pmioneal cavity ia invaded not 
infrequGnlly by way of Uie drnphrua'^, with jccnoral 
perltonidfi aa the occaAronal reault. lu pnt^umo- 
coceus pfeuriltfi the ciudate is frcijueutly uf a 
9crou(= cbarncitcr. Kiidocorditia, mcningitip aad 
nrtlxrltin ore frequent epm plication a. Conjunetivi- 
lia, otitia ntedfa. eulHueoiUE or vithcvituni-oua tnfiyy 
tiona, intramuKulor absecf«es and OAteomydiUa 


i,vA-fferfw,v axd rmrr.v/xv. 



hnfl Vaarvp- 

ma^ dcrdop. Tlio kidcejt anU Iner tuiuUy ohow 

Diplooonud jineumodi occar» u a couipJicahoa 
in typhoid, diphthchj^ tuboreuI^MiK, injluenuit crj' 
fripelas and otli^ jnfpetmnH, thn nrgajimni Cif 1h4< 
priiuATj infection also beicg foo&d in the Jtm^ 
Not infrequODtly Ataph^lococci., «treptooocci, .V^ 
cforoiruj tdfnr/Jta^u, or the bacillus of Friedlaml* 
cr. are fouDtl with the pueumoeccccs, Uie lallcr 
bcin^ tlift prcilamiuiitiog orgtoitm. RccoDt vorb 
from rtiippft* Iiulitntc (Flick, Uaix^ocH and I^p 
will] «a£g4?etA Ihat tlic pDeumocDCCua may be Rii 
pj:dling l'huso of pulmoimry hemorrhage m Ibe 

FfOphyUoUo ineoBUrcs aro U?^Iyof an iodivid- 
jml cliarjti^tvr. Out; »!ii>u1il nnt cnmfi iti iratitiitrt uii- 
nt^c-'iiinrj ly with Uiosc aufTcritij; (TT>m pnoimoiut. 
Th« BiiaceptJhtc abould be guarded against expM- 
ure; pneuinojiia nhoultl be connider^ jui a couta- 
irioue dipi?a?o. tbe patiente ehouJd be i^Iatcd. tl}c 
ijiutuiu jliaiiif*?ctedT and rooma cleaucd witJi moi»l 
nutiBcpticA tnttitr than by ducting and Fwesping; 
tho flick i^oro should be Hooded ivitb euulight, and 
tho mwulh* nt conrnlefwenti dfslnfocfwl. Fi:ppt*i- 
ration in public places ahoLild be Ifniit^d. Tu whal 
oxt4?iit tliG dnat-ladon atmoapliere which provalle 
in w^tti of uur large L'iliea U a factor in cauaing 
pncumonu ia luibnown, Voccinatm is Dot y«t 
ail <4Ub1iehcd prccedure. 

Il in pniEj^hb? iltut Hut ^iiAcrptibiliiy of mnit 
vQrica greatly- Under *<iiinl conditiona of cxpoe- 
iiTG not all contract pnouTYioaia, £Dd an Individual 
who c^pntually cortrad^t the disease inny have 
undorponc many similar cxpocurv^ proriously. 
Kl(>itipvrer intnalucod a culture of the pueuTiiococ- 



cn> which vroi virultutt for rabbits uader bis akin 
inthont suiFering more Iban temporor}- dieiturb- 

Rifcoveij seems to indkalc aii HcquirtiJ Iiujdud- KvnTarr. 
ity or rcs^stjmce which is by do menns permjuiontr 
and often is of very short durjition. One may ha\e 
u many aa eiglit or teu altacka of pneumonia, the 
intorvflls b^ti^eer nUaclcfi bumg from tbree to five 
^frtrs on tin? Mvtrftge (Griswolle). Wliat Uie re- 
coterj or acquired rCBielance depends on is a mat- 
1^ of murh difouieioTi, 

Nenfdd snd Hnendel believe tbat the antiboilies 
in pneumonia are inoctiv** until a Pt^rtniic ccnccn- 
tmtion h reached nii3 tJint when a high ^nongb 
detdopnient of aiitibudiea di^<:u]^. therr? h a aitddeu 
neutralisation of toxine with defltruction oi pncu- 
morj^cci Ipsdtng to Ibe rrm^, Tbpse mithr.fs find 
tbat tlie Acrum t>f petients, who Imve passed tbe 
ci'i«B, ia protective for uiic'7 ogniuFt mnny fatal 
doB«« of pneumocoi^c). Otber obeervers bave failed 
to find flnj evidence that tbe crisis ia due to anti* 
body prodiiftion. Tbe mark<?d leiitfn:TtopiB of 
pnevimunia, and thi> known pliagooylJc pow^^r of 
the leucocyte* for the diplococcusi, ^nggeat tUonziy 
th* importance of tbe leucocytw fnr rw'overy. Th» 
vtruiTiv of eunvalemwnta and nf iirkinizne HiiiinttU 
tbow no inctwLBcd bnctoicidnl power for ibc 
organiEm, nor ore 1b*y atrikingly untftoxic. Tbe 
opsonic pdwrr of Ibi- wn^m in pm-umonin in 
de<>r*flpcd in tho early *(npop of the diecnjio and 
r«a<^beft ita hefi^bt at tb« crisis and tho foUoving 
few days. 

Some of tbe ecnime which bave been prepared 
bavn bp«n uiu^d IliPiapoi^tkiillv in mAn, bi^t tlu^ re*- 
fiulta have not been utifficiently aafivfaetory to piit 



iliem oa a fooO U&ia, althougU some frnt-umbU; le- 
ports hare boan rivcd. 

Th? Gemm of Ro«m«T is obtaioed bjr ujuaonu- 
in^ (^IfTfrvnt kinds of Aoiaiala vltb Bvrenl ttniu 
of pnciimficoeou "J'lic rNC|>tor apparttus of differ- 
ent sirains jircbabtv differ; h^ttcv, a Mrum oblain^ 
hy lu^iiiuniiatioci witL eevend etraiDA probttUjr 
vFgulct l>o cductiTo ttgtinct a large \tiitiij of pvieu- 
mooocd, Furtliemiore^ aiiicv different mtimtti 
nifty reepoiul to immumiMion with & giveo organ' 
Uin by the formfttici^ of uiTibocepton with different 
com picjnfn tophi loiu hnptnphornf, a tiicoretif'A] ftd* 
nmUi^c is to be pained by mixing immujie «mme 
from weral BiLiTnala. 1*^^ Brnboe«picini of utte or 
more of the ftfninu nuj be ousccptibk to octiTk- 
tiou by th« eompl«mont of Wit piliont'ft bodj, 
vberca« if liiily i>ue aeriiiri uer« uaed the disncc of 
duch octitfition would bt^ dccroowd. I^bilcr, in 
«umm[Tt^ up Ihp rcmilU obUin^f) fn the trofltment 
of 34 caacs with lliia serum, finds Uie coufm of the 
disease! shorlent>d, tbe lomptiratnrc reduced iiul a 
It^m^inrv In limit the pxtnnsinri of (h(> dineftC* to 
other part* of the limga. Aocordiag to Xmfdd 
and Hai^ndct tho di^ndv^ntogo of tho TAriooa aati- 
«eritii[r4 H(.<8 trr Ihe fad. tli^t fliej cannot readily bff 
given in large imuugh dofts to be ufFectire. 

The Ferum ol pa^umonia patients «howfi on in- 
pn?[i»»!d ujj;ghitinaiing jxiw<.'r for tfju puuuoiorootTuav 
The mLuimum is rcncht^l at or near the time of 
crlaiOr but mroly has a bigV^r vnhie tban 1 to CO 
to 1 (o GO (Nfrufeld, Rovenow). U diaappeon 
quickly after rocovcry. In immunisuitl nnimala the 
Agglnl Inn ting powpr may ho piisbeil to niidi higher 
limit^H N'ot all sLraia^ yield a^^lutluma equally, 
find not oil aro nj^lutinoted equally by the aam^ 




«erum. AciKtrdiag Ut CoUiua, pneumococci f^ 
into <lif!er«nt groups, depending on their ftgglu- 
tJOable propertit*; the eume author determined 
the preeeccc ot grotip ftgglutuuDB in an immuDe 
uernm. Nenfelii stales that uvirulent strains were 
not ngglutirfttcd by the ecrum of pneumonic pa- 

Beginning with Fraenkifl (18S6). manv hate VB^^ii.e 
«hown tlio poitsibUity of mcToafling the res i stance 
of FiiiAceptible enimfila to the pDeumoooocna by in- 
jecting fiirt dend or unrulrtil nnJ Ihcr viruknt 
culhtrot; in this nay th^ Bnbj*?ct« rnr hn mnde to 
irithfltand many muHipbd of the miaimuin fatal 
do8c*. Itosenow lias heen abl^ to Beparale, by a 
pTOCMB of uutolyaifl. tlt^^ mflrtf toxic purt of the 
pncuraoooema, and th? bndi<!]B of the; o['gaiii>im>- 
By the \x»^ of tlie uon^toxlc part a? aiiligea. a 
more rapjd development :if aQtibo<li«Ti can be 
ohtninv'K pxppriirn'ntnlly. thnn ean be? optotH' 
plislwd wiUi whjle iin&iuijococci ; Hosenovr has 
mule thii fact the bd?!)?^ of treatment of puou 
monifi by mpnn= of injwtirti of thp Biitnlynwl bod- 
ftt of ptieumocoi^ri and ha* obtiiued enci>uragmg 
rftrolte. It t^ hop<'il that thie proofdure will bn a 
Talnable aid in haprteniDg the frlaia. 

iirttKK iNrhHTiOKa itr the i^xhchooodgdh. 

Uompiicntirii; mfcctiona by the pneiimocoecua 
during the conrae of pneumonia were nipntiored 
abore. Tbcy itiay ot'cur by way of Uie lynjpb 
cbannclft, oe in plcmritifl, pcricurditia and pcritoni- 
til (t-hrongh the diaphragm), by rontirnniiB eTit**n- 
Mon, n* in infection of the hrondii, noso and, F»er- 
haps, the middle car, or iw mctantolin tnfortions 
following tbfl invasion of the blood Hlream by the 


ixt^^vitOK AyD liiuuxirr- 

OTgasnoM. It ifl uadoublcdJ; lo the Uat nmm^ 
nuDcer tbat mmingitift, cndoearJitan, vthrititt 

Ko«4rii£ni Ift* itvIfittH^ from ciidocanJilJii CflW* 
pmumcv^oci^] diflvring firm ihi^ tinuit) type m lltit 

closely if} lilt -iirf«<r of lilocul-a^or jljiuth. Thcj 
jrrciw in ^^hiiinv nml prrMliin> I<«k grvcn on bk>od^ 
Bi^fftr platc4 tliAD i1«> piifiiTiiococcl of t1i« ni^tisl ijpc. 
In ADimu! ijKioiilatiorr n Icntl^ncT to Ioonhi« on 
i>m1nl]iplinl Eiirfflri^ i» «.l]fl^v||. 

Otlir^r infection* hy t)ic pneumocfxxruK occur in- 
dopcndcnt of tlic cxmtdncff of pnciunocia. Su^ 
oon^itiona are alvcolnr abstreAt^B^ conjuiK^livitijp 
d&crjCLjitUtb. AFi Infill uloer of llit^ LM>riii'ji. iJi- 
flammntion of Uic middle cur, ntcn:nj;iti«, catcri* 
tU, rarely p«rjtoriltfi, and pncuiaococcuc »cptice* 
mia vTiich mnv bo oomplicAteil b^ Enfeotlan Iii varU 
ou» orenn^. The eye b otpoaed to infection from 
without nnd tho cmr from tho phnryn:^. Primary 
pueumoooccu« moolngiliii oceurg both i[>OTa<I tolly 
and epiJeruicaUy, altliou^h tJie meniii^uciHXTin tv 
a EiiiiHi DkOn^ frequent cai]«c. Tliv rij^jini^in^ iiiAV 
j*Ain ontranoo lhT<iu;;h tlic niilttb cnr i:ir no«c, or 
throngli Ihe eircuktiou from a primary focu« in 
REiotlier orgaii. perhaps an luidJacovi-K-d focii». Pre- 
ceding and during nicninj^tia the no«c is tict in- 
frequently tho scat of pnciimococcufl rljinitifi. And 
ihu or^iii^iiirt inity be nirriyil from tbt noMo to the 
mejiiiigea by v/ay of tlic lymph channcla. The 
blood inoy hf infectcl tccondanly. FneAimococciu 
raoningitiK i* ulmoal invariably fatal. The organ- 
igni cuust'H I'ltraiiJc meningitis lew frequently OiAn 
the mcningococcuf. Infcctioo of the pcritoncnin 



vuy folloiv an UiE««tJDal infection \ a pure pucumo- 
coccUB inicctioii of t.!ic iftritoiieiim m the aWncr 
oi pnGHiDOTtia ie extremely mrc- Pricumococcufi 
infectioDii of Uie e}e, ear, iuttsliuea aiid perito- 
neum Are hkcij to be occomp&nicd by otiier or- 

Pneiimutvicrui conjunctivitis oocara in epidemic 
form ond (he Annie precautiona jihould be takcu 
to hntiL ii aft for the limitation of mSikamA con- 

^^erpiginouB ulcor of Hie cte, & progressive plug- 
rdt>n]c prvtrcu ill the t^'rrnra, is lisijoIIv (-iLue&d by 
the prn.'iiinivi>i'iiK iillliough ctlier organi^iriH Miaj 
U prcBi^ut. Knt'iiii^r Irt-ats the cx^ndition with 
nn antipnevinioeoccue £t-rum unU claims that hd is 
abju to arrest the pro<^G^ if the treatment J9 begun 
HUfliciealiy early. The seruio ia iojectod bODOAtb 

ir. OTBI::PTOtOCCl, 

Whcii wound mfcctiona. caeca of BcpLicetiijji and niitoverr 
pyeniia were firat studied hacteriologically, varioiu r*a*i"* ° 
rtHinrf wrri; iipplinl to rcrlniu ci*fci whicli wcrv 
found. Such were tJie Microsporon septUun ot 
Kleh» ntid the Coccobacterui siptica of Billroth 
and otlin>, E^aMeur recognized ^ucli orgam»m« 
ai^d cultivated them nt an early date, but O^on. 
in IftfiU to ISSl, minx ^^'" "pwly-d*'via»d technic 
af Koch, v-nff the fir«t to rccojrnJKe two *ortii of whieh begard the natnesof Mtrep- 
lociKi'i iitid uliiphyhji'ocri, Thi^ fiirmir grew in thp 
fomi of chnin^ An{L llic latter in clnatcra. In 1883 
Fehlei*rn nbiRinpd the *treptocoee;is in pure eul- 
lurpH from <a»es of etTaipclnn, Ro^rniinrh deter- 
mine^l mort* emctly the wgnifieftncc of streptococci 




ID wound iiifoctiofia &nd «optic«nu^, uid gsre to 
the orgaiiJHDi tlic iiume of StreptococcuM pjfogwmst. 
lilt; typical slr«ptoooccns in n ^sherkftl or 
vplitroiclaL coll, about ono nticroo in diunctor, 
wliJL'ii gfoufl ui tiie form of cbAlu» af larjing 
tun>;lh. Uivisiou tEik«d ptfto« in one dtroctioo 
only. VimationA in formf »iich &t diploooociit-Uk^ 
ccUa in paira or chaLns, or dongntcd cells reaem- 
bliDfi bacilli, n>praMnt acculectal cUgCB or snoina- 
lini m (IhiHiu]!- HtreittficCKvi cumtiiudly ii|i|)tfiir tt 
(liplococci in the blood and tiwufa of the infected. 
UiiiiKUJilly litrg^ (vllfi mfly be involution formt, 
Tbv JiDlculLy of dUtixi^ULbliinjf Un; pnettiiiococciB 
from tbo ftreptococous hu been mentioned. At 
Ofl# tiiii<» it WHS thought tlint utrrpiococci could 
be Mpftiatcd into tliOBC vliicli j;r?ir iu long cUains 
{8^ limguM) and ttio:^ which produce uliort chaiju 
(j?. (rrn^Lff), Although \}\o»* names Are sLIlI used 
for conveniCDO, they urc not well grounded, »iQC« 
Llii> li<cgUi of t)m chuiiu in not nn inhrrent prop- 
erty; one fcTDi may te cbftDgod into the other by 
oppropnat« mcthoda of cultivation. SimiltrLy th« 
5, ^np^<iii$ of Peli!c'i«irii jn not ii iGpr<cif1c or- 
^Qiam for erysipelas, einco strains from otlier 
•OTITCCA nnt able to eauae cx|H.-rirTu-[]lHl L'ryxipi^lai 
in man. Streptococci growing in nhort ehaLns may 
b« «n1tivated from the normnl month oavity and 
tti(!y jirc (ijiHully of Inw virultfNci? for aniinal*. On 
the ot^f^r hnnd, S. longtif ijt mc^ro often obtained 
from wound inf^otioos^ scplicemia and malignant 
toniiiMitiH. Cnp»iiljit<*(l fitrniiift of liigh vimlimca 
ere occasionally found in the body. Ordinarily, 
however, streptococci are not (^rrounded by a eap- 
Kiilfl, Thci StrflptiK-orciiK mitroHun tnny bo a pneu- 
moccccuf. AlUiouKh olrcptccocci *ro described 




whicli do rot Btnin b}' Oram's metlirxt, thoae with 
uhich wn «ru ominTrncfl invnnriSly ri-nrt ponilivofy, 
Strrp(«coiri nrc? rtotof irotilp, po*wjes no flogelln.' 
ard font] no spores. 

Streptoc<x^i grow better in a neutral or slightly t^«ii"»»ii»i 
alkjilino modiuai than in <t:iG of acul reaction, but 
viruleDW? in lost rapidly. They may be frullivated 
iiidciiiiitcJv in media which contain aenini or 
ueitic fluid, but C7«d here nruWoc disappOATe 
grmlually; fn-tjut-rit transpkiifulioti is necessary. 
In bouillon those atraina which produce eliort 
cbaine or grow aa diplococci cause a dilfuec cloud- 
ing of tht^ medium, whercoa those growing iu long 
^laioi sink to the bottom, leaving a cl«ar orerly' 
lug fluid. Streptocom domaud little oxygen, all 
are facultative anaerobe ami ^mo are sniil lo Ih* 
oblif^atc nnncrobcs; obligate ana^^'obea majr be eul- 
tiTAt«d from the vagina acd irtcetinoa. The 
Optimum tem|)efB(iire for growth ia 3?' C. 

WJieu dried, Hlreptocixxu live for -from Len days 
to KVfral wecka; they arc dcetroyod more quickly 
in the prcscnco of Hunlight. Susceptibility to 
ftntiJVptJe> dep<MidN at) fhe ntilurt' of the medium 
in whith they are auaj>e£tded or imbedded. When 
unprotected by bouiJIon or other fluid they nw 
killed in a few (Ccond« by 1/1000 corrosive sub< 
limflttt and 3 |X'r cent, earlxiltt^ fietd (FehleJaeu) ; 
when ia bouillon, by 1/lCOO corrosivij sublimate 
and by 1/2Q0 carbolic acid in tlfteon minuto*' Ly* 
ing on B mticoLJJ svirfflcc, where thoy art' mb^dd^l 
in mitntu or tiwnp fliildf;, thry nn- yirntiTlnd 
agninrt antiseptics to »omo ^jctent Thf*y arc fairly 
rc*i*tADt to heat, being destroyed by a temperature 
C. in oDe hour (v. Lingvlalieim). 



iSyBCTloy ASD IU3lthtTY. 

VinWn**. Streptocooci vary widdf in their pathog9tii^ty» 
CtillnrM vTuch Are entirely non-patUogenk tor 
fluiniiiU arc fruquiMitly cnltivttttid from unturo and 
irom mnn. Ae a rule, liowitpr, the Ijmg rhaiiH 
obtnincd from pathclogicat prooes&o* in man &re 
patbogvnic for rabbits luid mice. Their vimlonc^ 
is viT)' Inbile* Jind by pafsage through suitable mi* 
TtitiU (rabbit, mouse) it may be puntied to a r«ry 
higb poiiil; in doing this, how«rer, the origiml 
viruleDce i>f ihe cultiare undfirgocs inodiOcatioii&. 
yov iixtimp\^. Matmorclt 90 iDoreoAcd tbo rinjlcDOC 
<tf oiH' strnin thnt the millionth pnrt of n nihip 
ceDtiiiieler ^vas fjjtal for rnblit^. btti it }i3il h^t rla 
pftlhojfrnuTiiy fir iiirm, at shown hy ]iioi-i[UtioiM 
into <?ftrtrinrmiaroTi« putipnta. f\ei\<-p \h^ pntho- 
i:enii:ily *>f fulturc» U'T Liniinfllf is not a jrood 
indoK nf ibflir viru!cnc« (f»T mnn, Tbo*o tvM^h 
produce long Hinint* in lo«ilb>ri uro mor*? iiathn- 
j;cnic than tlio?t(? formiu£ short chains [r. Lisgcl- 

Pubbila AiiO mice fire Ili« iMMt flUfloe}''lible ani* 
mnlA. The mt. ^umcapig and «i^ iB<l larger nni- 
Risln, fts tiio hoTtv, goat imd flht'Cp, arc loss sus- 
coplitile A boLuUou cuhuri- of ^rUtdi from O.Ol 
to 1.0 C-(^ will kill a moiiitc or rabbit in from om 
to frttir dffva 1* f*nnfibWftd nf liigh in moderate 
viruknce. Virulent cultun^j cauau [4y*l*;[nii: infec- 
tion, rcj^rdlvif cf iUc- ntothod of inornTntion. 
T,C8B vinilrni ciiltiire^ pmdiJce change*^ uhicli rtrv 
more localiJi(.'d in character ami which wuy heal; 
fthtrpisf'i:^ >ir(*Jii" of nw*ro»t( antl rrvflipolftton* 

B»4A<otin. The ppopertittt on which the virLileuctf of ntrt-pfo- 
eocci depends ttro littlo understood, Th« conflict 
of fiT''J>*'^" concerning mnny point* ptobablv de- 



p^nde CD i)io (ISO of dilTerejiD strsiua of th^s organ- 
ism in cipLTimciLtnl ^urk. Tlic iiniouut ot cihIq' 
toxin which virulent stroins conti^irL la subject to 
great variaiJone. Amnson found practically none 
in the killoil celU of % very virulent fitrain- it 
seem* probable that Uk (mdotoitiii in rattier cue- 
cuptible to heat, axncc cultures wliiofi are killed 
by mild metliotls. uj by cbloroform, arc uiort toxic 
thui thOM whidi aro kiLbd hy h«ai. The Hitrates 
of old botiiUon cuitureB aic jnore ol' Ic»a to\ic. A 
strong 'toxin" wm proparGd b> ManuoreU by 
growing n vinilcfit utrmn in n mixnira of serum 
and bouiiioD for three niontha auU Altering the 
oulluro. More rix-eully lie ueen a meiUuDi contain- 
ing glyisK^il jiiul Ivudn. Tutir ^jrei^ipitalcH ftum 
fluid cultures have alao been ohtaiued. Bouillon 
liUratc* of virulent c^ullurea afier two to fourteen 
lUjB of growth hjkvf \ov toxicity (Aronsgri). 

BeareUktt, and ktcr C. V. Rueibgor. aliowod tliat ^t^jpi***- 
rinilcnt wtreptocofi^j produL-t a hemolytic toxin t^nott^rttr 
when grown in vonijoa heated berum*. ItucdisEcr **' "' 
proved that [hi« [lOfiioh-^in (Btroptooolyain) is a 
tme toxin, fjussfssing n haptophoroua and toxo- 
phoroui strui^ture, Thia discovery haa an im- 
portant bearinf* on tbc fact that the blood in fatal 
rtrr[*locoorti5 infwLioni!, especially in rabbits, ibi 
often more or le«8 lakcd. Strcptocolysin U dd- 
ltroy«d by a leonperaturB of TO' C. in two hour*. 
by peptiu digeaUnn. di;l<*rinml<^"< r.i|iii1ly ni rrili- 
nary temperature, and is non-dialyeable. Cert&in 
normal serums oonfain ontiBtreptoooIyKtti (Rim* 
diifcr). Another sicnificai)! Uni i? that vimlwit 
ftTDiDS, wh<^n ;;rown in ^erum nud a.^citir fluid, 
product a inil>*lnnrp whirb kills l(*urfwt(>s and 

inhtbite pha^ocytofrit. TEiie may uxplaiu the fail- 


t)iF£CTiOX AJfD IMMVtfirr. 

MTt- oF leucocjtfA 1o uW up rirulnnl ni^ninnft, 
vhcrcM noD'ViruloDt vtraiikft lire r^diljr pb«^-v< 
Mted. Von Linf^elMieiiu «latt« lliat ntrefm onUU 
viitt*d froiQ mbficvk or din>nic procciifca pttxlttce 
mor@ m]u1i]« to:iin (nature hdIebowii) than higblv 
virultfiit fitmn-'', Nut all tojdc filtrates euiiUin 
■ttrcptocolvvb, tJi« hcinoljBin httt^ iodcpcDdcot 
of othi^r toti^ cnnditiifrntf (Sim/in). Von tin^ti- 
heiiu ooncludeft Dial the infect iorifaew of rtnrpto- 
cooai ift not OKplain^d by tho tojii> properties which 
hsv* Wn i!iTtnnn«tni1i*f1, He? \ny* Kirtvx nn tb^r 
resjfitance to the twctericidfll activitJM of the ti»- 
nui and tbfsiic^ nLii<3<. It i« «Af(^ to 9ay that tip to 
lhi» prf?iipii1 limo thi' r^r^ntfal iitxhi of Ilie ftlrtrpto^ 
cocL'KS lia* not been ilfuionj^trated^ 

Stroptooocci are tho frequoiit caase of wound in* 
fitdinnii^ i\w mml roniTuori camn nf Ijmphau^itiA 
and dilT^jac Inflominatioiia of the ffiihcatancoui sad 
interninscniar coDn«ctiT« tifiBuea (cellutitifl), enAo* 
melnlxH aiul pucrprrnl w-plirtmia, emlocardUU 
nnd tonsillitis ore often tlic exciting orj^micou 
in pnGrnnonia (lobular, nsiiJilly), hronohitis, 
meningitis, indoniitiAti^n* of the eerous ft^rfac^es 
(pencurdiiim, plcani, pt^nionciim Joint*), ontentij! 
And suppurative processes Id U^c middle ear. They 
nn tlip ^xdHsivc rnu-n* ^f prywipcJns. iind wrion* 
nttomptja hnve ho^n made to phnw that they aw 
I'tiologit' fnd'HB iit wsrM fc-vtt nrul rfii-umiilit' 
fnfcr. The ^ttx^ptccoocun i* the mr^t common 
orgsnUm fnnnd h; th« ki^toiK; of imp<>ti^ oontfl- 
^iot^. allhau^h it niAy ha iiitA«d vltTi oth^r h»c^ 
imsu 4!«pocmllv the »tnphjlocoreu>, 4Wurri»c ■" 
mixed inffction* in pminifmifl, tnhrmrW'Jfl, twar- 
let fefer, enteritis and otlicr pioceMCA. they cbub* 
fn'KTe anil ofi^n faraL coin plication*. 



Kot ol] stTfptocooci arc able to caujic crTBipc]iu> 
and a tlreptocwt^ua cuilivutofl from a case of ery- 
npclsB is not &ble to cauee i\\ii •Wt^tsts iu uU iu(3j- »>r*i«>eitta,' 
Tidualfl, Funh^nnoK, cuilur^a obtaiutyl from 
rjthpr iiuunwii (phl^^moD) rnaj product th« dJB- 
ca*c (Koch ftni Pcrtmschkv). Kwh protiuceH an 
cr}>jpolAtona LDflammaliou witli etuplivl^^^oireue, 
II has been anggeeted that ttreftoootd nbich 
r«U£c erjaipelas. rather thun tiom? otli^r proi^tfttj 
do 60 becaufiC of eome peculiarily ill their Tiruletce 
or in tlLe reGietauce of the imiividual, or perhapc 
both. Another feuggesiion is riiiit this tjpe of in- 
fection d«p«iida ou aome pcciiliArit> in the ekic 
tnd subcaUuwQs tUeae of the susceptible^ Th« 
conditions are obscore. The inf^tion atrium ia 
not alvaye known. In facial orysipelaa e&tmiM 
probftblv is gainetl throuj^h tJie mucous membrane 
of the nose m many inrtonccs. Kr)-aipe]as is a 
tfoimd infection in most or all instfinces, although 
the atriluii often tfntapea oWr* alien. Tlie iri^irn 
he principally in the l}~mph spaces and jnterspaees 
of the rniinwtive tist«r, Thpy nre rsMy to be 
cultivated from t}ie scalev or ^ floid of bliMera, 
but may bo obtoinod from ikm which ii cxcittd 
from X\w lioriler of the inflninetl aiefl (FeliT^iwn). 
Tbey probably are not excreted through the un- 
Qpolcen akin. 

Erysipelas is an inflammation of Ute superficial i.Tn^iwa- 
lynif^aUoa of the skin, while in l^-mphanjcitia the *"*'- 
doeper lymphnti*^ ar^ involv*?<l, Thrcmbosia of 
^ lymphatiT-' vesBtrlH, tMiigesliitu uf ihu ailjactnt 
hJo'^ reaseU. eansinjc reddened «trvaks and loeal 
hvmotysi* [f), sr^ diatingtii^hirg local featuroc. 
Hetaataaea occur to adjacent lymph ^andu and 
the infaetioft may beeomi genaral. In this proeesa. 

tMwwcTm% Ajet» tUMrvirr^ 



i a f j Mti cw w , thraiBho«b of the 
■Aj occur, vUc^ mmy he the tnt 
tirp a tke p i^ d TtM a of pjenui ynih mvltipk 

OUhbti* nsT alM be cou«d hy the etaphvlo- 
ftli«« cr itttatioa mith tb« httrr mov be 
AB a prtatiT flTVptocMrv cvlluTitii; 
pnvh-m! bj tht itnptocotxnt m^; 
eitWr W prinnuj or mcam^Mry to infMrtion in 
oll«r r«it» Af ilir kxlr. It i« moetl^ of tlie IcJialar 
typr IS tke w«witULC of ««jtipir fori, vrhkb ptv- 
•nt « «toaMli nr£«oi ra Mrtioa A^d «n: T^ry ridi 
itt nth. It oenn lent fraqomtlr in tli^ form of 
kbv fniwIiditiBa. ftlid nf^ fnqiiaitit an n iriv^ 
laftfctioft in pBLUiwiiiii couMd h% the pncuino- 

Stnpl*ovn« iiifec4l«a of tht TotigK in pqU 
aoBBij bilocvlosi it a jcrioitt sad frcqncot com- 
pikiitiof] of xht Utter Jwii C - It pfodvoM ft ttptK 
qittditjofl, i&Toliw adjuvot bakhv tiww, ind ite 
HSIfr ta cuaiqg cooMUd«tHa um) li^uefactiou of 
the tivso^ predn|nici of licmorriiasau In mU 
tvRf^ the fttrrfktMOfm* b void to ikliibtl tlir 
fro will of Ihf tobrn^ bociDniL 

Pniurj cUvptocoecos ■Mohtgitu i« raro or of 
dottWhil orcnrrpncg. Tt frvqivmtly tf unxindnnr 
to otilifi mr^ift, to injumii, aikI 1»» Imtr natwl 
foUoTin; lonsillitt!. facUI rryiptia** puKumonifl. 
fiidoc4rd)tif And >f ptrt of « pyoimir procc^c^ 

StnptAcocci ftrt al lime* the nnwe of mtcHtla 
in rhililn^n, t\^ mdjuniniilioii oftrn Iv-inj; tumii- 
Imuious anil acctiiDpiKikd lijr <la9i|iiuiiuitiuu of ilv. 
epdlhclium fln<] by licnrcrrhajrof, Jl M not infre- 

J^'iHtii'rOVOtVfti IM'JiCTIOX^. 


quinily foJIowoli by pgrjlcnitia imd Ai*|4it-TTui«. 
Vinjlcnt nrgnniKniH pmbnhly ivnvh tlie rntr^Hnr^ 
thmujfh luifk in many tDslanc^'!^. E^clifM^icli friiiniJ 
iitrt{>tocoeci in ncorly uvory wmthjU' uf milk wht(>li 
lie exaimDcd. Difrc^tive dielaibanci^s due la oilier 
eaujwft predispose u infection. The orpanienna are 
ni^wHy ftltt'jjys pn^in^nl m Ihf* intPntlniH oT the 
ndiilt. but vaatf coteritiA lt«s froqivcutly than IQ 

'I'ho normal vn^na docf) not offer a good cul- 
ture iiicdiuiu for pathogenic bai.:tena, altJiougli 
ftlrcpiooocci an: occosionallv found there. Tficy 
oc^iir moTo frtqu'*nt!y in Uiosc w)io hn\o Iflm*- 
children- The vagina tends to purify iUelf ine- 
ehanicallv and hv tlie aeid nature at its Keerotiona. 
ir Uir sw:ri-eMon for any rtunon btcarnt* alkdline, 
us in catarrhal conditions, or if it oonUias Idfioil 
and ecnim, which provide a ^ood culture modmm, 
vindrnt sf N-prftcopci prolifenir{?, Infoetion takes 
plnfe ihrougli drniiilod ftiirfari's iifid loiira; endotne* 
trifis^ metritis. parornctritiB. ^a]pfns[ilift. pen- 
toniiif^ ai\<\ SK-jtflf may follow, ThronvboAift of the 
bhiorl vriett^U ttmy be Mlowvd by the development 
of pntiinioaic foci, 

Slrcpiococci arc probflbi> always prpucnt on the 
lonails, the mncoua rnttmbrAno of the mouth, vory 
frfli^ucntly in thi- sputum mid (ni( iiifri^ipieutly uu 
the muL'ous mttnbranT! of the uiiierior iiarcs. Vvi- 
Bumnbl'' *hr-v prolif'Tjitt' under inflammatory con- 
ditiona from whntovBr cauKp. Ilnrjing in the eonim 
and pksnm whit^h <'xmh' a nii'rltLim favornblr? for 
growth ami ihc dnvclopnmnt nf virulence. They 
arc of ^cnt signifjca^i;^!! in Acvcrc local iatlamma^ 
Ciontf, M in diphtheriri and Aoarlatinflr and when 


II ml lllprna. 

* Vtfrw 



•Ter. Noi infroqiicQtly the vc^teliona contftin 

S]DC« 18G7. wIlCtl Salisbury deacriljed a fuugiia 
which ht oaUt(IJf^fnf>ioffiff (panfltofnj.inany micro- 
organiRtnii hjivr hrrn clrjirrihiv] nud mltivuterl fmm 
the jo»:it*. bluiKi, tiidocartlillc and perioarditk' 
Icaoof unci from the tenuis in acute artkuUr 
rh«itiDat)Ein. AnioDg thi'm were ihe "Monadincn" 
ftf Klels (1S7S), short bacilli bv Wilson (1686) 
and oth«re, 8lflphvloci>c<M and stmplococci by 
Wpirhftdbwiim (ISS5) iind by many tklhcn:, und 
nil lumfroliir Willns rr:s[^]ubling Dint ot aiillirax 
by Aclmlrou (18^0), Streptococci havo been found 
more freqwentW thar other organisine. Tho ba- 
cillnp of Anhnlme Required cons id (.Table pramint^jme 
it one time, brinji: found in rlietamati&m in a num- 
hor of ca&cf. but it has beeu found since in other 
condition*!, and normally, and Achnlne bimsdf 
gnvft np hU origlnnl rdnima for ite L-iiologic 
£igniflGanct>. The organifim, possibly, ia identical 
with a. iieroijenes capsulatua of Welch (Harris). 
Many of tho observat.iona are of little value, since 
the cnhurte wen? made ptetmortem, wfien eontami- 
nations and ogonnl inva^ioQa by other organjmna 
could not be oxoladcd- Tho conditiooe were very 
nmfusiiig, liowevLT, siitcl* (lie injwiinr of pnrp 
ctilttjrc« occasional Jy producc<i arthritia, pen- 
carditifl and cndocurditifl in animal*. Tliia vm 
the ca«o with a ahott anat^robic bucilluH ar diplo- 
bftciJlua cultivated by TFiirobix, and by Tnl>oii!ci, 
Co^n and Zadoo (1«97), 

In leST-SS Trihoulel and Coyon cuttivHlivl from 
the blood of five caaea of rlieutnaiic fuver a diplo- 
coccue, pure enltur^e af which cauwil orthritja. 

■ iiniHlll 

iV/JCTTiOV XUti iMMtfHsrr. 


etc, ia nbfaiU. Siaiilvr ol^vrrtatiiMu 
b7 W«ftpfaiLL. Wajncmiann na<d 

a4 Ifes poMJIiiHty of prodvcin^ {wooa 

«( Ansitic ftrer bjr the ioocula- 

dl^n» taba ahknla hut bam wrIJ «s- 

Ah-fco<^ llw ofguiiM wift cftlled « 

h5 iJm AManrtn^ tt t*ii not bo d>*- 

hw tfc# «nCBfti7 ftraptocDonu pra- 

^ fttltviml tats. IVac dJocomicB do t^ot. 

^ the* {MftSrciUr ftr??ptococcu4 oo a 

h«H» «• tba cvne o( tb« diaeue^ aum 

ffMi jmarn wo M Xcm tre ifale to emM 

trtlttitk ta nbbtU (Cole, lUrrw). 

n UmI viraknt sUvptocooci fnwu vti^lDrpr 

Imty t HulttaHatt Car iem* mrfiec*. Thii 

fr&m. tW frpqnncY vith wfikfa 

tftc^ m Larolred in 

u Btt. Tbp Ticw of Si 

aw «f tW Mivv ■inlfaitilliwii of Arfptwixctti 
tansMs" (Bvria), fii»d« foone jB«tifioittofi in 
tOMiIl<ti rith whidi tbe ^^ 
Oa neoter; of alniilocooci 

fbmi tte dir opMcic Uiilicttf for Jl. r^> 
(B««lti<, ra>-ritiMi «»d Tain^t for 5fi 
m^ai trvta the thioal of a |«tieiU wtl 
ili^watTiH umI for glw ^ facacotf pja^ewn fol- 
tM A* *^** vrmrsr (JiLiinf allarli* of rlwQ- 
wyto^ tv ntfn vith joint ^jiaplomf aitJ 
hM^ llfrrituT IW tiKWv va* rabonnnol nnA 

XO0C aboiVQ noniiQl. Tdc iadiccH for Staphy 
lococcuB auraui, piiouitioooociki and a atrain of 
Sirtptocficcttg viriflarm fvnm a uonniil tltronl 
did not «how a lamtion from the DOrmaL 
Agglutfikiii) ooitimoii to M. riifiwjtatirtis and itlrep* 
tocorci wprr fi^niul (o follov Ihr- onmr rmjtst* aa 
the cpFonic index. Jit^iuuiDi^ation of robbits vf\\}i 
M. rhfuTunfifiiJi n-Hiilli-iJ in thi* fi.»'niaLinn of op^a- 
niiiii for both Uii* organium and 4">Vr«pio<:ocnM 
p^iiffcncs, Theei' Jindinp^ vould indicate that 
strrpUinji'E-j jiImv mi j-hw'iiIhjI jwrt in wnli? urtii'u- 
Ur vJicHmntisni. 1'iic fnct r«moin«, liowcvcr, that 
stroptooocci cannot ahvaVB be o\ilti\»W from tJio 
luioni of rbciininti^ frvcr; hvm'j-. it is powiiMn llmt 
the or^nifun may c^iat aa a mix^d irfcction with 
more or ]\'^-i *\'a*iiin<yy. and Ihat the r««tl cat.uo fs 
All ynl nnknown (I'hillip). 

The tloory tliul ecarlct fevor is of atrcptococcue HiimUi. or 
cUolo^y hrift bw-D h<?ld pnrUoiilnrly by Babw, Tv'^ii»"r*!r** 
Klein, M^rwr, Guidon and Drt^in8ky and l^omiuei'- ''*"'*■■ 
feld. Somo liave held that etroptococoi isolated 
from tht iliswist' show iIiKtinrlivp pn>|jfrlip* juul 
dcicrvc tlicnaiiicof Sirepififract^u* scartalimr. ThiB, 
fiuwev<T, li nut agrL'(*il It) by mfiHt bacterioloj^isl^. 
the organismF not HilTcring from strcptoeocci ob- 
tained from vannna aonrcoe, The orpaniBme are 
not fciund i-oiisUnlly in (hi^ mUniiimtoLis prupUoii. 

Vinilcnt atrcplococci arc found on the tonaila 
fllmoiit invariably lu sc^arlot fover. In &5 per oent. 
of thf. cjLM'jt 11 mriikhraiK' Is formed (Itankt), and 
this is often diic lo the streptococcus, which is 
flonietiuiv!<, howi*verj ii9»:(wuil<?d uilh diphllicTle 
jnfccti-on. The frequency with which atrcptococci 
invade tlic bloo^l during f^^arlct fever is related to 
ihe aewrity of the di<i'»*i.'. Oc'E^iiitonallv thor are 



liiMVmrX TO 8TJiBPT0C0C0U8- 


ceniLiu Atreina liavc this odect (Zogan, oitv<l by 
V, Lingeli^hfim). It ift not«d occiwinnAlTy thnt Input; 
tDaprovcft or actually iicaU following nu att&ctc 
of crydjDCtoe. A ropuloU cUoct of it similar uaturo 
in tuberculosU of Uie limgE vns menfiDOi.*0 ubovt?. 

The olinicfll ob^ci-ration thut nn nttack of 
emiptiaB often eauaes a deereflse Ji: the s.he of £iV™wu 
muiignaut tuziioiE. ^speciaJlv sorcoitias^ received 
somti condrmaUon from the vjipeniiiuatal work of 
FeMdspn, With the hope of reproduciug erjaipe- 
laa with pur« cullures, Fddeiecn had inocuUted 
■trc-ptococd into thoite fulTtfnDg from euch tumora. 
Amoii^ six piitioiU eo incx^ulnteJ, a Oe^^reiise in tlta 
■lie of the tLunor vfm acted in five» lulled cul- 
turcfi wcru tried vitliout 9Q€ct. Coles's mixture 
of killed callur^ of the j^treptococcua and Bacith^^ 
prodigiojfus reccjvod rathor cxtenaiv'u trial as a 
fnbetitutG for living riiltur*'^ of Uie etreptocmccua, 
anJ iu raaD> imtaDc^ impTovcmect and Ctch 
curoa have he^a »?port«d. Otl^cra havf) hnd no 
fnvorable ri'Siilts. Scnn ustd the prepiirution in 
twelve caecfi of inoperable aarcoma 'Vitlj negative 
re«ulla," The BadUus prodigiorxxt ia supposed in 
*omr way to iiicTf'fljic thf etlKJirj of the aLrcrpto- 
coccuB to:e]n ; it contains a tovic prott^iu- These 
toxins seem lo Imvu no influem^u ou c^areinomas- 

Conccmin^ the Datura! ausccptibility and im- 
munity of man lo mfeoljocB vith Xht atreptocowiua ]^ 
little {m knoiviK U KtL'nm probnbl*^ tbat the iin- <«»jiiit 
impaired mucous surface rcsisttt invasion hy tlie 
organiema which occur constantly in tho mouth 
rarity; tiic piiy*irnl profpHinn nf th? intact *i»r- 
facc, the rapid dpaquamalioc of epithelium, the 
rapid excretion witli the »aliva, the inhibiting id- 
fluraci; of the wlivu nn the proliferation of bac- 

•I %m^*9\ 

txtMCTiajf xhD tMMoxirr- 

leri* And tbt deilniction of Imeieru b/ Um hnwrv 
«ftM Tluoh coneumljr ftpiwr on tlie ntucoiia boi^ 
f*ra ftfo proMflj tmpoitsiit ftctorv in this lonJ 
mulABec Coo^<«tioii of tbom 9urfftc««, «p^ 
euOIr 111* tMttil^ from ni..T cau#c, u from eX' 
iramn;. or Uie occarmio^ <tf •om« uth«r lurecrtion, 
R0 fluij be tlir am in vcmiIH fever, may lower the 
local protwiiTO powervv And, u «Utad, tbe aaum 
•ad pU^mn wlfirh 4-iiriie in i.-nUirrlud coE>ditione 
or other infiftiniBAtionif, proxifle a tnodium whicK 
fmroni Xlw gmrtb and dtmlofWHOit of virulciMe 
bv strtpitomrj. 

CooMcniog Uk ooaditkine vliicli, in tlie bodv, 
taVUkgmhe^ loitaion, vfc arv largely id the dmic 
[t hn» bom iiBpoesibk to demoudni*! Hntit^xic 
»nd bMlcricidal autetanen in the nf>rraal ^emm 
of Rum^ Strrjitocorri grow fn^\y m frGsb nomi«J 
dtntm vbidi (Wbtainn mo kuci^oyte* (Weaver and 
(j. K. Huodifccr). FhnfocytotM of etrepforccd 
Aral rante inwlrr the obwrvation of Met^JmikofF, 
vho ID ISST noted it u a striking <}Ocurmicv iir 
emipeUcL Only the fnicropha^ took np the cocci. 
Tbp murkfJ letirocviiiPiH which i» not^ c-Imically 
sagKedtA. bat of coxinc dooa not prore. that the 
lf«coCYt«< take an active part in tli« dc«truetioit 
of the roori. HifwrimmtMl worhc nliotv'ing; such a 
rcblinn>liip i^ not lacking, however, Bonlet ci>n' 
cTud«d thit aU the protection wh:eh guincn-pi^ 
and nbhiu show a^inst streptococci is due to 
the pli«^/tt«. In octuol infection etreptococci 
have otter tif^n fc^nnd uithin the Tou<"ocvto= of 
the b^ood and tiillnnEtniili^rv F.vudfltfis id. F. Rut'' 
diger.) Kon-Wrulcnt or woafcly virulent irtrflitift 
are phagocytiwd moft readily ihan the viniTent if> 
eipcrinioatal work. Buoiigcr also dtmoiiHtrated 


tUUVMiinti^ Gh- ASitUALH. 


rancliwivdy tlial the atrepl.i>coccI tak^n uji bv po!j- 
morplionucicar tococytta may k* killed by tJiu lat- 
tw- IlcnoD thu evtclfmco in favor of a prok^/rthe 
rOle by Ujc leucocytt!^^ ia irtore t!ian preaafiipUve^ 
KucJiger BU|s'fi<fa'e the imporlonco of the Icuco- 
cytic toxin of thi? atrcptococcUH for the devi^lop* 
ment of JufecLion. II may dtlier kill the Icuco- 
cytos or cnusc nef^Ativc chemotaxis, and vnder Ihcee 
rnnHitioiifl proliff-rnfion if the co(*ri mny prorpr^d, 
WpaTc-r, TunniciifT ami Bt'Ughton hai^u nbown 
thflt tho dofpnfte '>f th? hndy jiirnitiHt otr^ptoroci^i 
depemid on tho j<owpr nf |lllflgo^'vln^i^4 iitt th(' pari 
of the Icucofrytps as wdl na tlie opforiri, hciico thr 
ovtt Hint ion of the refii^ting |ifiwcr of thr bwiy iniut 
tw iiiFHHureil h\ ibe burterlcidjil piiwt'i' nf wIioJi' 

The strt-ptot-ocfufi usually is duaseil witli tbojie 4oii*itwi 
orgonisma, infection with whjdi does notcauM the 
dcTftlopment of losting immunity. A cerlain 
amount of immunity prohnhly U eHtahlislied^ hnw- 
evfT. This is auggeated by the results of Fehlei- 
«?n, vho could not ulways cuuae Kcoond atlacka 
of erysipelas by the inoculation of pure culturta 
into tlie fiustcpliblo. It is alao su^fpeBlcd by the 
fiflSQ with wbidi relutively high rcmijitaocc' L*au bt 
produceiJ in aniroala by brief imtiiunizalioiij A 
jitreptococeua infeeljou of the liorac whioli oocure 
nalurally ("nnitt-") ia Hnid to prodHfff immunity 
wM<:Ii lafitfl for a ytar or two, 

Ono may immuniKo nnirrmU eSth<>r vilh lostie 
flltrnfpft (ir with kilhvl imd living f-Hlturi'ii Thr 
filtrate* are much low effective in producini* im- 
munity than ihu bfloforial colls, and in the bandi 
of many no immunitv whufrvirr could he catalv 


rlAv at 

XTrsmur ^D tMMCariTT. 

viA ctthttna. It tfmui tiisl 

piotectm povttf for olMr 

«f kfm n nJ»je u On thb 

id whtt AnstM, TmmgTitif 

tb« nmWne* of wfakii h« 

t» A wjha^ poun b]r PMBtag tbein 

tW JMu— mm, particulariy 
i Brti a c t pnttctiTc povcr 
Svcfc aMWM, boTev«r, fcntv 
IVY pov«r «|aijiii Uw ptrtkn- 
w u«d for imaittmntJCHk, «1- 
«f Axmmm li not d^voU cf pro- 
fldktt pttlbogenic •timm*. 
of HanBonfc thm tit di- 
1n ^ hBDdfl of Humorek U 
m U^Hy y w t wt iTc in uubaI cxperinento; otba* 
It vMottt nlnt. The ntdiod of U«> 
iod ol Aroomi toU not ail> on the bant 
^^ tlttt dniM oi (be kij|^«M Tiralcaoc will iprc tbfr 
■CTitiif omBs, b«t &bo on tfav «««impitiiOB oF 
tfao ■bHt of oO palbogtuic at f t p loeood. It aU 
4i« tl\kv ifi tb*Kr bMogie ft&d patbogoiuc pr^or- 
xim, ft MTsB «1ikfa proieds ft^mct one shonld 
piotoct «|vnat oIL A« pointed oat, there u ftt 
pnoMt not wffd iB t fvond fbr ooou^^ring the 
Hwpto c ocfj of irjilpftlw^ teariH fenr, rht-^unun 
tiMi. f<V^ «tc. m iodepcadcDt q)oc>e«- By ou^ 
tltstkw ftod p oOT go it is poonUo to to modify taj 
ofw of then that it b EndiediigvURhtr tram tU 
olfaav, ofi the hMs of moTpholofrr nixl petho- 
fnMtf, Oil the otbn hmnd tbn^ ftr» oot ^ 
nlvntirol in ivine tvtj important propertieA. For 



exampla, not all strains produce Uemol^sia to tbe 
satiie degree, and iliey differ greaLly in tlii^ii sua* 
ceptibility to the nction *>f an agfflutinftting aerum. 
\Vp have also to remember lliat paUiogpTiidtj for 
auimalfi is not a retial>Ic mdcj: of pathogenicitj for 
man- From these confusing ccndttioDs we can 
only regaifl Hie question of uiTrtv or mulriplidt)' 
of 3tn;pto*om as an open cnc, wiiich may be d^ 
eidod by future EnvestlgAtions, 

The seruuifi of Karmoruk and ArouHOu ace uiil- 
volont soroins^ a single strain being usuU for im- 
DiumzatioD- Certflin iiiV4;stig^torft, b<>Heviag in 
the multipLicitj of streptococci. utiliM aeTcml 
fltraifiB iiL inmiinizatloQ. Tho f^Tuni of Denva is 
obUineil by iiiununiziitg with several strains the 
virulence of which has been firtiticiaily increaacd. 
Such a eemm wouUl, theoretically, have a wider 
rniigv of fiction thiui jl utiivuli^ut «-iuiii ; it is poly- 
ralcntn Hnving in mind the fact that poaeiiig a cul- 
ture through rabbitft increaaea the viruJeiicc of 
the organism foi tlic rabbit, but altcTs it£ v^nilencc 
for tJie original host (man), Tnvol. Moeer and 
Mender prt^pare dprunis on a ■]tfrei'i?nt hnaib. 
Tare! employs ecvcral Btmins nf streptococci cu!- 
titated from pathologioul prooessee in man, avoid- 
ing aanh a^tonilioQB In viruK'nf^i? a^ would be caused 
by paseiag the cultures through animaU. On the 
ossumptiou that SL7«r1vt fpvrr in a stiv[TtnL-o(?Ln]s 
diaeaae, Moscr immunize* horacft witli atrainfl 
(about twenty) which Arc cultivatc^l from tas<i? 
nf Guirlef, fever Tn n «iniilrtr maiiiipr, Mmiwr. 
Buppomng that rheumatic fcTCr ia a Btrcptococciia 
iafftcHonH immuaiiM vilh a number of strxiua c«U 
tivated from the torwila of crnaes of rheum at ism. 
Both Mo*eT and Mcuier avoid pOAea^c in order to 

I'nlT-^lf 111 ■ 


i\nx'TJos 4AX* tujicsni\ 


nrtAin ihc orlgina] biologic pro|WTtIei of the cni- 

In &ft-.aial cxpcrimcnu, cono of theee Mnau, 
And |knrtieiilftrlY itioL of AroDeon, have ezhibrtel 
ftron^ pTQtcctirc powc^re. ArooaonV vcruin id 
■looM *>f 0.0004 \o aOQUd ex. protects n motuc 
AgaiiiAl IvQ filal doacfr of tbe eticptococcua given 
iwGQtV'fodr hoiiTV U1?r ihaa tiic seruni. A acnun 
of w^iu-Tl 0,01 4rxv |irotoAA ■gmmtt n tia*n knaTii 
to bo fntfl) i« coiuidertd of nomul streAftb- Tbt 
prutent cj«tqqi, then, is of tT«my* lo tT«nt3-'fiTf- 
folil \m\m\ )& HuniL- iuKUuicea luiJiimU can bt- 
sflTc<l vhcn the eomm U mk4 womc honra after 
infcctloti, but tbift period u a brief c&Cp 

StntAnent^ coooemiDg the Tilne of uitiiitrcpio- 
-ThTiFApr, jxKxu* mratin in m«tiDg humiLn mfcctioiu om 
vorv eonflicting. The seniin of Mannorek hu 
been i^rea more genernj triil iUxtn luny oUlgt, ftikd,] 
the rcfulu hATc not boon «ati»facloij. FaTonbla 
efTreCftT 'u^^ ^ ih^ lowering of temperature and 
iiuptotcmcitt in tb« geocrftl condiliou, h&ie beeu 
reported, but tJi« fcrum powcuea no dUtinct ciir«*i 
tive power in e«:abii«licd Liifcction&. Kocb «0i 
I'ctruKhky den> tlitt it Iiaa a propbyltt«tic power' 
in ipxptrim^nlAl iTynipi^LHK. Kcchcrich, by unng 
ilic ftJL-Tuni of MoaoT, and Baginakr, by uaing thnt 
^»r1rl "f Afonfton. ol^Mrvcd a ohorteninj; of tbe courvc, 
n reduriioii of thi- frrer niid gr^toriil i[npn>Ti'rTn*nl 
m caMv of ecarlf^t fever. Uoscr claima tbat it re- 
^lu«a Uie mortality of the diteasf. The um of 
jinfiftlrr|]inroi'ru!» scTUtn in \hr tmilmrnt of tCHtlet 
fever ^ODS not commit one to the etreptococoui 
etiolog[\- of Ibe dlfcase. l«1 ratl^er to tho irapor- 
tanee of atreplocorcu^ complicntione ; hence, if llie 
rliuif^er of thete eomplioatioDi can he reduced hj 


■41 !*■ . 


Bcfwii Kftnling Uie mntin inj«ctioo i>f 
■Uiyiucuiu lure bm codflictia^. It hn^ been 
hod thai tfa» mc of gtUctoae m t ii)«aiu of kill- 
iaf the fiTvptacficd rmlt* in ■ brttnr pi Ma i i n tioa 
«f aa4%iB»c pnpcTtioi than docs the oee of heat 

Wcmr roaehito UM tU nw of tMrapntie 
iaj«ct&OM of fd■rio«l^kU!^1 Rtr^ptococd te of 
f«]ttc ofily in raWaito uvl chrooie atreptocoonu 

Tl>« aggtotuufaOit^ of str^ptocood from differ 
aM atNLTca^ and eren from Die mim aonrM, TBricB 
a great deal A1m> iho nomu! senuiu of nun and 
Ml»a1f kaw a fariabl^ agglutinating pos^ foc^ 
Jifeait ilnuDa of rt rtplooooci. B? inamunisatu 
vilh a jcit«B Btraiit lfc« aislvtin&Un^ povcr u iH' 
cnaoed. tmt nol aaifonnW tor all bctsIdl Com- 
SMad; the ctnin uwd for immaaitttraii U iggli 
lUMtod oan atrooiKT than hetenrfogotis vtraii 
itic kttvr aonatinea onJergoing im agglntmatioi^l 
whateicr. Tlicw TiHatiAna do not dppenj on dia- 
eotmbk difffrcoces in Ui^ cooci or tJie dii 
vUcb tJivy produce, A jnTCO antiftrcpl 
aanm doci not aggtutioale equallr all ati 
hoa Cttflea of scartet ferer (Wtaver). Abo sn 
tococct rai7 grtat); in ihcir abitity to ttlmolale 
to tli« toraatkuk of ^gi^lutiniiu. On tbc vhol 
those which produce loi^ chaiiu are more ai 
tibk to aggltituiation and y^t^A stronger wraj 
tiutti Hwae with abort chains (Araieon, 'J'avel. 
V. Liftgebli«)in). ^ pMeafte the ^rglutinatij 
propprttea itmliT^ rilhor cnmplct changM. The 
orga&iani Ui«f) produDca a AtrDng-n- agglutinatiag 
amm and i» agglntinatod mora m^^W^ b^ thia: 
aamm than the aamv atrain which hnd not baanj 



pamd thrmigli Rnrmala. If passage is difloon- 
timtfid it ri'vr^rb to its former coniliUoiL. 

The vflrintione nre BOch that the fi^glatination 
reaction is of litlte r>r do value in d&^erentialiuj/ 
ilifTercnt t]^pes of streptococci 

Ae to tbo clinicnl VftJni? of tlio tcet for the diag- 
iioKta cf m'tirlt-I fever^ flie eo[idii*ioiiji of Wenver 
rony be cttcii: 

1, Of sir^ptofoooi ciiltivftted from caaee of aoat- 
tniJn^i, Komc wrc ayglatinJited Iv almust all w*ar- 
latinal ecrn. bat at liilutioua var^in^' from 1/60 
to 1/40(10; other* ars oggluliualed by Uio a«me 
aera with 1^86 constancy and at lower dilutions, niu^ 
many arc not agglatinAtcd at a)]> 

Z. Streptococci t?ullivatctl from caeea of scjir- 
Ifltiritt Eire aggltitiuali-d Ijy wrn from cases of lobar 
pneuwoaia luid eryaipelafi tit about Uie same iilu- 
tioua 13 by ecarlutinnl acra, and in the cofie of ery- 
fdptiUs evi-n at higher <^ili]ttone, 

3. The tame appcfir* to be tine of typhoid fever 
icn:m, so far as limited teate indicate, and to Al- 
most the ««mc «^ttf^iit of pntTpcrfll-fi'viT wnnn. 

4> Tlie ngglutiration reaction bctwci^n the 
glreplocooci cuHivutt-tl from euncs of scarlatioa and 
Ih^ ffrum from east's of scarlet fever ik lu no way 
specific, and cai^ not be of any value ua a mcana of 

By growing slrqitomcci on n tiirdiiim which 
contains scrum (actum bouillon), Ihey form fewer 
and «hcTtnr chntrii; aiul ure better soiled for aj;- 
gluttnatioD teaU^ 


staphylococci are spherical cells imm 0.1 to i>.!t 
mteroni in diameter, typlcttUy. nod by light vtaio* 





mg BJ» oftKI MOD to CDIMItft Of tWO b<nuiBplltfV«», 

vkich aro septritixl bj c (l«jio«to cleft la pu^ 
(Ikoy are fouii<l in «di«U group of two to niiw or 
tttu ociuicaully «s diplotocci, totrd<l» uy rciy shnvc 

Tbe3' are liuuhaul grower* on atarly M umJis 
vrhicfa on tuiuble for b«ctcrUi preferring, bow- 
«Trr, & di^tly ftlkalint reMtioo. Grovih ig bail 
in iht prtsonce of ^nygat, but proliferation occvrf 
m iU tbte&co- Sputtim, ecTum and cuKitic dttid 
■rr fAVomlitff rnrdia^ and in th? Ia>^ two thtj cocci 
may be agglutinated. An alkaline reactioa la pro- 
diteod in litmva inilk, and the caaein U precipitated 
and partly digrctcd. Tbe produc^i^n af n proteo- 
Ijlic ferment h ftbovn bv liquefaction of ^atin 
Afid tho fonnatioD of a door Moe about the coio- 
niea vhen grown in platea which contflio coognlat- 
ftd seniiD (Locb, cite^ by Keioter and hipatcin). 
Allmmin is Htangnl intf) pfptotip, \AiAt di4lii>- 
guishw between a ferment wbidi li<pcfici gelatin 
(fjdatiiUAd, a "coUolytic" fentkent}, and onfl vhjdi 
digwta albumen (tn-plicr fermenl). Oelatiniiae b 
pnaient in titnphj^iococcua Rltratca and normoJ 
eanim« arc rich in antibodiea for it- A fat-^plittin^ 
fenuent (lab ferment) ia al^o present in the 
flllratefl- The fact that the pua which ia prodneed 
iQ sIflphj'locorGus iufcetian dcea not coognlat? may 
bo liue to (lie adioQ of the proleoljtic forniect. 
which digeata the flbrmoKe^' 

Van der Voldo hod noted in 1$94 that "alaphy- 
lotoiin" (MiiplirI(ifY>«-ui filtrult^l cause hcmolj- 
«*- Neiwcr and Wcch»berg. in 1^01, by growing 
Iho orgunUm* in bonillon of suiiiMc alkalmitv, 
obUinod horaoljtjc filtrate*, giting the name of 
itaphylolvwn to the bemolvtic principle The hemo- 




Alt ^Bbal pitW 

famn «f ft« Innntw Mid vfiMwiw). The T^ri 

plmA U a« kamidiv tt tki« ivM»tuK<^ » not 

iIhIbiMt kB*n, 
• 'f Tbe iDBSj TBittitt of tlkt ittph^lococcv* •!« 
-^tl^ dUTtftafttiflM oe tlw bMb of patbe^smdty, pag- 

mmt frniBttlon. UquetactHni or iXMi'liqwfwCloB 



of gclftEin, and otlicr cullurn] proportini)- Th« 
Staphifhinjcrnn ttihus ililTt'is fioni tlii? Siaphyt(>^ 
f-occju aurrus onlr in ib iiiiibility tn form pi(:- 
iii«ct, fttt(3 it oannot be madt? to ac<quir& this prop- 
erty. Pigment is fiimiml incknl nliuiKlniitiv on 
potato, \rh*rrojis Utile h fc»rracd on biood aii-uia. 
Other i>i|ntieiit-foTTilnft varielk't ary: S. c/feva 
flavua, 8. pyagpnrt rtfrttnii, S. suirhitintiJ' wnd 
Micrococcus hcmaiodM. The iS. epidfrrnidis albus 
*f Welch IB of bw virulenco. W^ichselbaum 
obtAiDtii a S. rndo\-irdititi^ riAtjtxttiV ficut a caie 
of endocsrditia. Not ail of tlici^* varieties produoc 
Nuluble tnsins. Tilt* pigment of .S. *iHrvuj i* nn 
eiCTcHoE] product tthicli i« formed onlv in the 
prcHmoc of oxygon. It it insolubJc in wntcr, »oL- 
ub!« in alcohol and ctJicr, ariU girw tbe reu^'Hrtn 
of A lijHK-brofiie (i. e., Llie |jf)finL-iit ma^ be *NiH>m- 
ficd and give* the lipoc^anin retctton in which ihc 
pijrmcnt tnrne blue when tr^aled with coneontri- 
teti Ftilphtirco ac\ii\. 

Anidi" from wide indiviilunl Turinliojifl, the re- 
eiatjince of etaphjlococci to beat dcpcn<la on the 
coucontratioD of the eutpcnsion* the nature of the 
mHinm (whothtr wnter, gelatin or pus), and 
whi^Lhtr Uur ttwt h a dry or wot oni' (Keit«ir and 
Ijiptftein), Eighty degrees centigraiBc for oa^liaif 
lo on6 hour kill* them ar<ler all conditions, fttid 
flO" C- for one-half hour fcilU many utrain* when 
miapeiidf^d in bouilW, Tliey are not killed by re- 
pented frce^sing and thawing, and arc very roaiflt- 
ant to ilcaiecation. When in tlie form of fin« ^^^ 
tbey dJe in twenty-fight tlavi (Kiratoin)- Ke»i»t- 
ance to Ihe action of sunlight ia variable; »om9 
atraina arc killed in from throe to five hours. 




SSFtX7i03/ AXI> iMMCXirr. 

Supli^lococci liave fkirly high nvdntmncv 1o anti- 
•optm; vben <!r)c<!, corrwivc tabJimaU (l/lOOO) 
kilk ih«tti in two Uj lhr*« houra, Mid vbtn im- 
bed<l«d tu pttft from thirtcrn to >ut4irn hours srv 
h^quirtd ^Ottoviao), Hcthyl ak-^>lx>I, tincturr of 

iliKinfvclauU- Mv'rli)! violet in a ililotioD ol 
V10,Q00 kilU tlt^m in from livo to Jiftc^o miAuU* 
(Stilling). Fomia]]ii readily hinder* ilevtiop' 
lacut, but iia bacteriddftl power in low. li i* 
Jirlioiilt or impo«sibk lo ttbetilm vounda i&f#cted 
trilli th? flUph^lixnochiA hy mvftns "f AtilJeL-|jiioB. 

StAph>lococci are very widctv diAlribtitcd in na- 
ture cind ar« to b« found conelantlv in tb« snper- 
Hrial la^era of Iht* epjilerinitf {S, epidermidit at* 

i.»n«444oM* In infG«:tionc the atBpl3^1oeoocu% altracta Urgie 
^*' ^«^!^a'br nuinbvn of leucocvtcK, aiid tite pun docv iMt coi^* 

lAt«. Tht ^ubBlanccT vhhh attrncts Itmcacytm iB 
heat-retitsinni. «iiK-e killed cuUurea will cauje 
i^bitcLtEac*, )q all but tb« inont aup«rnciaJ Iwona 
A ^AfActorittic rocult nf infection iB Uiat of 0911 
necroHia and Ihv llc|iief action of fjasuea. Ifeuacr 
nnd l>ip«tcin state that the nccTotiiiuff itubttanct 
i« a soluble tojiin. giufi* crnlhire tl]trntc« caufv 
marked lJel■^u^itl uf (he iijlcmal or^aiia when In* 
jcctc<l {liver, heart, Iddncy], "Hence in ttaphjlo- 
fnyoi^flis wo cnn difltingui**h two oclive ^uhetuncm 
(v. TJiixcUlirim*. Ihr linifilrtclir iuli.iUiwi- i:i the 
lifidio= of tlj<^ coiri nnd tho mnrf- iirjiorinnt ffihibl? 
«tiiphvlotokiii tfhic-h e\erci»ier» nut t^mlv a lucnl but 
rtlw) a (Tf^ncml t^xic arlinn on thi? SodV'' fNeiwer 
jind T.ipDtoin). 
Anriuiii DAvidmn ]]Tci1urpil amj^loid d«^ueratiofi la 
uMAn^ mbbits ard mic*^ by 1li« iuJeoti«>ii of Imttf^ cuUvrM. 


arAPHyioaoCiJV^ lliFKOTJOIfS. 


liUllr of 

TUifi was confirineO by Lubanicli^ who fuuticl Uitf 
condition most rauiiJy pTodaccd in the chicken 

and with more diflk-nlty in ih& mouae, rabbit an*i 
Jog. U rareW lestillfi if stjppiirBtiou is avoidaU 
Killed euUurcfi mny be used. 

Rabbits and inii^ are the most susceptible nnU 
Juala. The suaceptibiliiy of man i» much greukr 
Tho oigauisme arc moat virulent for rabbits when 
inject«^rt imlravt^nou&ily, »nil a vHrit'lv 4>f Ii^r^iofw 
max result, aa nbaecBsea in various portfl of the 
body (ejipcciollv ttic kidney, heart and uiuwlea)^ 
Hribriti*, cnd<>cinlili^, etc Thry an? \vk patho- 
genic wijcn injected iuto tlic pleural or peritoneal 
i'*vjti>*- RkibbitK iirt* nirely to be infetted by Uie 
l«ediug of culturce- In cxpcrimc-ntal infections 
dvj^QCrattons of tlie a\i« cylinders in the white 
Hnd gTiiy tnntlcr, urtd of ganglionie cvlh, Imve been 
noted- The virulence of i*taphylococd U subject 
to great variationGT and it may be increased by 
pajUH^, In pnssing n cukiire tbrcutgli the rAbbit 
tight time»t> v. LingelBlicijn reduced the fatal doiie 
for mbbii? fram 5 e.c. of a ^'^hour brolh culnire, 
to l/T^O <^,c., but 6 rorr*'3|y>ndiiig increww in virn- 
JcDte for t\ic taoMSQ and guin^-pi^ did not occur. 
ViruloTicp ffir aiiinials i e* net a fgllahTi* indent uf 

The etaphylococcuti \8 tho most common pua iiir*oiiBB« 
limdun'CT ill muti. Th^ moHl fre^jueat infer*liuri« 
•re thoKc of thi: 9km. tbe ot^anitrms gaining en- 
traooo through tho hair folliclw rather thnn 
thiOQgh the fcweal Out-U (Fmiw) . rcviultiiig in snch 
oonditinrid at ncrnc puatuloA, nhaccse of the ekin 
und fi]hrutnm»:iiia ijivitip^ fiimncl^ and carbuu' Hkin. 
HtH^ They art found aimoat cansUutly in tlic 
Irnonn of impotij^o and often in pure culture 
Th^ hfi\p \tpfi\ miiHi vminlpd w* 11 cJinse of 

>u Mjib, 





tenant ADd thcjr iMf be UDporUnt w a cecondfti? 
i^rot ia Okie oondtbon. Tbc ordiD«rx n^m^ prolh 
Ablr H not panntie m iu cavuo, hovcrcr (SoIjou- 
nud), unl Nei&wr and Lipttcia <3is|mitt tbo claim 
of Bmdei and olhcn Uiat ccabcnn jm^kIdcviI by 
ftUphylocncciitt ftltmiN is due to pr<NlQctA oX ihc 
microbe, Thu ooocliuUui ii«» justiliod, siiuv ib« 
UDif rwilts v«rc obtftincd with pure boiuUoa of 
ilinilir alkalinitjrr tho property oould not be de- 
itrored by Viit, und atitUtaplijrlo(w»Qa wnni vw 
not nMr lo prrTOQt the deTmntXtit. Fttnnele* nuj 
be prodcce^J bv rubbinfc Tiroltmt L-nlluntt tnio tb* 
iHn, s&d aUcGMM by lh« injocLioa of micuU 
juuottabi. Tb« atuphylocoociii CAUcae pumtesi or 
flcropvnikat conjunctivitis rvUicr iuffv^uepUj. 
Primary iafectloEts of onviti<« vhicii cornmun>cate 
»itli ttic «uffacc, aa tlie autruiii ni Highmore, th* 
middlo car, toee, bronchi, lun^ And tubeimtooA 
cavilfoe, are not unf^ommon, and mUed iofcctiou 
with the etaphyloooocus in the«c lotralili^.^ i§ tbe 
rule, rcpirdlen of the primary cauM. Infcctaon 
nf th9 tTiiicntiH Atirfiirra ic \cka common lltao of the 
tkin* lioircvcr. It rarely caua« aphtlioiu InflAin- 
ination«» anjrlnai, pacuroOTiin, cutcritia and cjs- 
tilli when LDmixcd witli otber organUnu- 

SUphvlonKXiiA septicemia of ^reat riruJeocL' oc- 
cuioually folJovB primary infection in other part* 
of the bodjr^ It* womul inftrUotis tnniiilliHA, pueN 
poral iuffction (rare) and the ao^alkd maJf^ant 
cerbundM of tbc upper lip. In such infltancc« a 
UiTOnibophlrbitii^ maj- \v thp ni(tnji« by whicb the 
oTfaftkiua tre pourod into the circuiation in lar^ 
nmihbt^ra. Inflasimationa of the aeimta iiurfaci?0, 
a« the ]Ueura. poritontram and endocardium, an^ 
fiMjr tuiwajy* but follow syetcmic infcctioa; tbc 




■ ■>fTVCll>U*, 

eDilocflnliiiFi u^itally i^ itlcerntiTe uid Igbi.18 t^i 
m(^tati1atic foci of iufcction, Stapl^lOMflel havu a 
particular affinity for the bony tisgues, especially 
the bone marrow ami the periosteum; they are tlia 
mofti common agciit m the production of oeteomyt'- 
liti£ QuJ cauae Uie tio-calJed periostitis albuaiino^a. 
n is tliou^lrt thflt tlii^y n)a\ iwrsisL in houi? ittiuri!^ 
for u period of year& and later start up a frceU 
prcceai. Thev invoU'e the Joitila Iprs frequently^ 
hit hflTe been found, preaumnbiy 'as sectmdary 
ftg^ta, in aputo rheumutum^ und as the ^trimary 
cause in pyemic aij^w-rs^cs of t)ur joints. They are 
found o(N:asioijflIly m aWpsftOfr of the mammary 
and parotid gtanJs, livtr, luu^n, uud in pyorrhea ^i**^^ 
alveolaris (rare). The cnltiration of staphyloeocci 
in a pure state Irom thG ti^vee does Dot of neces- 
liiiy iniilicnte tli>it lli<.'y Hri< Lhr^ vitwritinl orgnriisni 
in the procew (smallpox, rhei:mnlirtni, etc,)- P''-'- 
tiotu infectioiie by many organisms, and likeviee 
trauma^s preflUposH to IfFtulinnimri of the alaphy-* 
lf>eoccu3- and any infectious propcna in the skin ie 
likely to be invaded by these organiama tecondanly 

Infections with lliu i»tnphylococcua arc cliarac- ii*u>MKi>to« 
turned by both loeaJ and g<mcral leiicocytoeifi, the Minmanitr, 
inea) ]eikrri('}'toms being a i^art of the Huppnrallve 
procew. As stated nljovc, the dtftphylococciis coii*\ 
tains a tharmogtabilc constitUH^t, which exerts a/ 
positive chemotatTc effect on tha leucocyfeg. Al- 
though it is poafiiblc to consider the accumuIatioQ 
of the leucoeytet merely as the expreeaion of 1}\\b 
affinity, k has bei.'ji shown with sufficient cU'iirni^ss 
thftt polymorphonuclear leucocytes are able to in- 
gf^t liTinjt Etiphylorneci and I'lM Ihcm.* Thev 

Klfvli la JSar 


lytfEVTiUfi IAD tUUVfifjy. 

isaj b# fo«ad within the IcucocjU* in botfi natunl 
4Di] erpenmenUI infcctiWDa. Wben i&jeotcd i&to 
thfl pUural or pentotieal cavity of the guiii««-pij 
phigo^rtoaie j» veil bc^D within onc-h&lf hotir 
an<J roact]«« it« height m four to live hours. 

Ex|]vrui)eQl» wliidi aviv Iiegtxu lij vau ikr V^^ 
in 1894 <icmoiiftnitc the bactcncid«] action of Icn* 
■:tiidHi*-. coc}'t:c eiudaUtt. Th« ftctioo is uoi «o stroi>g in 
till* cvll-ir«e exudate fia vhen the leucoc^lot are 
prcacnt, fin^l wlicn tiic Jcuoocytc* arc c«iued to dU- 
iQlegnto by eorae m«Ln^ sc bj ait«nial« freedng 
and Uiavii^, iritumlioD, the action of Icucocidin, 
or trcfttmcnt with JittiUcd wat^, tho bactericidal 
powt^r of thi.* fluid is increaml. Prwufitably the 
leucocytes dicvrbarge their bactericidal contents into 
th9 nurrouuding lluid ai A rcfult of mch injti- 
fic«. The rtAture of ibo bactericifJal aubAtani.'e \b 
uot known oxacUj; frofa tho fact, hoirevcr, that 
[ruf'tK^ytes contain complifint^iLt it Imx h<-vji nuggui^u 
ci that Uio)' dicchargo ttus complement vhich then 
act* Avith ambooeptors in tlie aenim m dt«tTO)'ia^ 
th? orgntiinni.v It Is j>a««ibTrf Ihut Uii* rxK^^^i brfore 
they art taken up hy the icucocyto have absorbed 
amboccpton and after th^r lug^atiOD are vnacepti- 
ble lo tko option of tlnf cmUictlltilar complement. 
In contract to the distinct bactericidal power of the 
tcueocyl04 Mtondi Ihe very tow or entire absence nf 
n ffimilnr nction by botb normal and immune 
aenun», It would eccm, then, thnt tbe most powt^r- 
ful agency in natuml raiifttBDce to Invaaloo by the 
»taph>'lococcuflt j» repreiented in the plinp^cjtte 
and bnetencidal activities of the Icucocytoe. Opeo- 
iiins Ttn- i-AH"iituil for phagocytoHio, 

In 1?&8. Itich<-t nnd IK-ncouH ihowed that it 
wnii poMibli* to incrertiw 1h? rerictflneo of the rabbit 



sgainfit t1i« «tflphyTocoeciiA by immunizfttion witli 

pure cnltorca/ 

One iriay immDnJae dther with living or killed 
cultures m with culture iUtrateH. ImmuniKatioii 
with thG bacterial cclla must proceed slowly iD 
ord«r td avoid killing the acimnU. When fiUrAlcs 
containing leiacociJiu »r staph viol vs in (hemolysin) 
xire ueed, aiititoxitiB for these Eubelout^es are 
formtJ- The atitiataphylolyEiu ohlnined for one 
strain noutraiizca the facmolyain o£ all strains- 
The most prolongeJ immuniKfition with bacterial 
cellft cau»e& no HppreriaMe iiDcreuge in burtcrioly* 

The flerum of one who has recovered from a 
atipby]oGOccua iDfection, or Uiut of ininiuntit^d an< 
tmale, U protective for other animals; 0.1 to 0.3 
cxv of nn immune senim given subciitnneously 
proicdod mice from a fatal dose of coed given 
two hoiire later, whereas other mice were killed in 
from S lo 13 lioiir*. When the serum was given 
S4 hmirfi in advftTicc of tfie culliire, from 0.08 to 
0.03 c-c, fiaveU them (v. Lirigeldiclm. cited by 
Nd«MT). The rwulte nf Petersen and of Prowth^^r 
were eimilar. In spite of this ralhcr strong pro- 
teclivu netioij^ immune FPi'ums have little or no 
CDTfttivc power 

No cicorcr explanation of the action of the im- p<*fer#iM 
ffren* serum b given than that afforded by the ** *"*"■' 
rxprrimenfa of PrrJsf^hrr, who injwted giitnea- 
pig¥, rflbbita and mice with normal and immune 
forums and follovp'ed tMa ZA hour* later with in* 
ocuUtion of the cocci into the peritoneal cftvit/. 

nfrRcrtox Ann iWMVhiTy. 

Thirty nuDiitM After injection of the cocci tlie 
oxudiitc in oil AciniaU showed an ODormouA Jenco- 
cjlofits. At first ihty irere chiefly mononucVi!4rrc, 
but \titt gate pLftce to poljuucleArs. In the imj- 
mili vrliieh had received tho immano eenuD, mae- 
tive phai(ocyto»:« had occurred, aud in the oourve 
of an hour vory iw cooci were eitraceUnlar. On 
th« other hand, prbctioalljr uo phagocybw had 
taken place in tJic animals which bad received the 
QorniAl ecrum (cit^ bv NeiiaerJ. Vjmlent 
&hiph>loeof«i werv taieu up Ivtss revidilj- than 
arirulcnt. Such resulta sujQccat that the protccliTe 
power of tho frruTn ia dn? to it« abilitv to etimnlata 
phagocjtoda. and i\m in turn depecda on tiv 
incrcaKd quantitv of haetcriotropic oubsta&co 
forin<?d in i\tv wtmui as thr rr«ii1t of immnnizatloa 
(Wrijrht end others). 
VBH4B««i«ib. In the hant^s of Wright, TaccinatioD with killed 
ciiUun» of thr j(Up]iyIfKT4)Cnu)( ha« l>ceTi veir »;uc- 
ceufvl in the cure of obAtiiiat€ cawe of ecne, fn- 
ranculoBit and uiaitv oth^r chronic dtafdiylonx^cnp 
mfection». Boiiillor culliiree are grown for ihnt 
wecJcB and then killed by e-tpoeure to e tempera- 
tnre of fiO* C. for ao hoar Tn on!fr t/> rontrol 
do0ft^, tlie vaccine le elnndardized hr eetimatfuf; 
the niimbor of bacilli in mi(i\\ cubic centimeter. 
This )( dnne by mixing ^qiiiiL fiuantltiffi of the 
raccine with normal blood, ant], after ^taintafr a 
preparation on a tUdn, di>termininj7 the ratio of 
Oowl to MTthTOcjte. There hping ahrurt 5^f»00,OOn 
er]ribn>cjte» to the cubic inillinieter ia normal 
t^OOJIt til* ni»nibor of cncei is rrndily n*okonml 
from th? ratiii uliich was found. From £,5()0 
millions tn 7-50€ mUlion! of cocci may be piven 
in an injeetior. The quantity to bo ncod i" 

Qi'SOXiV JIi£*£X. 


i1«t«nnmerl by tJie effect whicli an injeclion bft« on 
the. opsooic eoutont of the pationt'e serum. If a 
mitable dost has been given, Uiere ocewra a ahurt 
urgatire phase in which the opsonins are decreased 
in quantity, and this ib followed by a rather pro- 
longed positi^'e phase when they lindergo an in* 
crea«e. If too large a doee ia gircn. the ne^tirc 
phase 13 tJtaggerated and prolonged. Id many ia- 
Klaiic^ it has liei^n na\ed that improvement and 
r«coTei7 go hand in band vith an incroade in the 
op^ionins. Aa in atrept^^pof^eu* infot^liocs the total 
reaieting powtr nf lliu hurly il^'p^'odn on the vfliia- 
tioD in the capabiJity of the leitoocrt«B to take up 
and digest cocci ua well m tlic op«ouic action of 

Th« normal senimfi of oifti) and many animsU 
may agglutlnHtt? the btuphyfocoi-cua. bat with no 
conftancy. In &nc inrtancc humnr serum n£:ff]nii- 
nated in a dilution of I-IOC (Krans and Low), 
and tinnurtl woat SHnim iu a dilution of from 
l-W to I-'IOO (Ambergor, cited by Neicaei). Thff 
MTom^ from case* of staphylococcus infection 
(e. g., ot^teamyeLtis) »nd of highly immuniAed an- 
imala undergo an incrcaec id the quantity of ag- 
giutinJDS- The agglnti nation luaatly la strong^t 
for the homologona fitrwn, nnd if other strniua are 
Agglatinatt^d equally it slgniBes a close relation* 
ship to tlie hnmologous fltrain. 

From tl]C fact thnt only pntliogcnic *tmina prO- 
dtire hemfilysin pn<l Ipijf^^ciilin, Neisser and 
Ww:h»heri^ tonsidere^] Lhem ajiecificnlly different 
(wm non-pnthogcnce FtmiDQ, Thia ricw is borne 

t by th^ rnsTilts oM"ined with the aggtutSnaticHi 

8eniinrt ohtmueil by imTniinitation with 

pathogi^iiic ulrciri: have a much higher aggl^tJ* 



tUFBOTiOJt Ayo iMUVKny. 

QBting i>ov^ for lliOM stc-aiEia Uina for uou-pAtW 
gcaUc TAri«titt, imd th« conrerve iA aU« truo. Tho» 
are, bowercr, nuuf Tsriations in th^ Bgglutinsbil* 
itj of the memberi in e«cli group, a fact which ift- 
dicatos viiriationfi in the ri>ci>pt07 complvjc of th« 
diflcrent fctiaiiie. It kas been su^c«lcii Lliat i 
polytiileut aarum obtained b; imniiuiUitioD vitb 
% auflHent vnTia^- of pMhotCf^nii^ Htntiiv will b« 
afficicnt in ditTcrcntiatin^ the latter from noo* 
pnlUo^enic varifitiG^ bj moaiu cf the agglubna- 

t]0» tl"«t, 

VTriglkt, noting an incTcaee in the agslulinatiog 
pow^r vh^ii pitiGUt* txt treated hy Me tii«thod, 
L^ii«iilo[^ that tbif inrrcnN^ is «n index of the im- 
munity which w cstahliahed- 


For some ycara diplococci reacmbling the gon^ 
coccuM luid the nie:)STigccnC(!ti« mf^rpbologiCAlly and 
in staining h>4ctioti» have beon found in tlie 0fm- 
tutn by a number of obaerrerej and lo this coccus 
PfriffpT piw. l\\p. nnrnr of Mia^tait-r^is mtarrhniis. 
It is frequently found in tbo respiratory pusftfoa 
in iiitlu(<n^-11i:« uifoctioL« and other inflanama- 
tory condition*,, nnd otx'nsionitlly in pneu- 
monit;. It znav be JtMociflted vith the inflocnta 
baciUuH or the prieumococcus. Among 140 c>M« 
rtf di^rpKr* nf tlifr it*pirAtory pa»wigi>* flhon and H. 
Pfciffer found U M timea. and M- Neiftsi-r demon- 
atrftted it In l^ cauw of whonping-caiigh, in 
one of mearioe and Murlet fe\fi-. and in 
two of diphtbem. It loa» it^ifioancG iu relation 
to thew diHtftiww, hnw<'VL*r, titu't* J\h\M\ fonrid i* 
freqacDtty in the mucu^ of the normal trach«a. 
and W^ohMlbaum ciiltivai^ it fri^qncntly fr^^m 



Uic heiiltJij imeal fo&wr. According to Ghon, 
Pffiffj^r aiul Sederl, 'WiVrurorruj* i-atarrhftlis, 
without the flBsocifltiou -^f other microbe, ia able 
to ceuM broDehilig utiJ pnt-'umonin with the ullm- 
caI type of pneumonia due to the paeuiuocoocu^- 
Th* eymptome caused hy i\i<i Micrococcua catarrk- 
alia do not form Ji oljnif^nl fyp<*- They resi^mble 
infections by t}ic pncumococcufl or tlii^ bacillus of 
PfeiScr (Joflu^n^fa)" (dt9d by Bczancou aiid de 
JoDg). Others Jire nnt so jwaitive cottpernmg Uie 
pathogenic properties of the or^aniam, Ite ctio- 
iogic rdle ie i^ot yet well i^stablighed. U has little 
pathogenicity for uuimals, ulthoiig^Ii peritoneal and 
pleural irfcotion ia pi>eaiblc in guinea-pigs, 

rt differs from the gonococoue and meoingwoc- 
cii» tc certain calturnl characters. 


A. Neifiser dls^rovcred the gouocoocuB in 187^, Th* aone^ 
cultivated it in 1834, and deuionatraled its specific *"•""■■ 
rdatJon to gonorrhea by the inoculation of pure 
cultures into the liimian urL^thra. U is u diplo 
C0CCU4, young pairfl having n figurenDf-cight con- 
tour^ whereas oM&r pairs show a typical biacuit 
or rnffir-hfHn shjipe, Th(^ organism is non-motile, 
haa no flagcDa and forma no spores- It cur he 
eultivated only on mfhlia which contain serum, 
axcitie or a ^imilnr fluid. Mr f^iiiirc tn »Uin by 
Oram's method ia of jff'^at *lragnoetic importance 
in t1i« eEaminatlon of urethra] discharges; other 
organism? rwembling the gonococcvni are found in 
Ibo urethra and vagina with great mrity, Th* 
renetion loiev iU dt^prential value in (he exainSna* 
tion of «ccr':ti<in-^ of the now, month, nitd, to wnric 



Mud K«llftl* 

COi tnd tii« Microc^cctta ^ai^rrhalis mny be en* 
FMiBHriHU. In the purulent siag« oi a gooorH]i?«l iuiectJou 
(be ooDd) uc found tlmout cctirdj withia Uic ten* 
cxN^tffw, wlirnw in ij^rlier eUgCfi, wfaflo t]|# du- 
diU]g« is atiglit aoi of ft moooflt chatacler, uiJ 
tbo durinj; oottvaleMCDM, nbni tbo aecretton 
■gDiD becomes muroius, tlioy are lirs^ljr extncfJ- 
lular, Il3e3r an Dcver wilhin the Dncld. 7^ 
proecH ic odo of actire phagocyto«ifl in vhieh th« 
cocci p^y a paMivo r^e. Th«> occur iio>t ontj on 
tlte raifaoe of Lbc «ptthcliuQi, but penetrate )x- 
twi^^n anil bcimih tht vpiihi-ltnl cv^lld. and ovfn 
iiilo die adjacent connective tia»uc. 

In culture Di«Ua ^vth it slow and acanL ami 
cullUKft rarely Tjv& longer thiu one or two wockc, 
unlcA'^lhvvtrrlranepIantcd in suifAblc fmh media. 
On Itw latter tlioj msj be carried tlirottgh raiay 
ganarAlinnic nithout Ifxing tbeir viruloncCL Whirti 
dried Lhcj die very quicklj:, l>ut maj- livo for wimo 
houn on hnen (lovela) of the ekia; aad for 
ltt<«ntT-foiir boon m wann water They mra tvry 
viiATfitible to lempciatureE nhoTc ^3' or 4.1* C, 
and £hoT «%ry little r«&5st4acG to antiseptio), par- 
Ikiilarly th$ dlvpr uJtsc 

Tht conococcu decrtta bo loZuble toiin. but 
ecniaiiu an eadoroxin or lo^Jc "protein" vlil«h 
cavara local and general sympltJins in both man 
a&d animals. Dca^t cultures produce an inflamma' 
lory eJtndate in tlic peritoneal cavity of {guinea* 
pi|^ and m\tt, resulting in death if the doM la 
lufflrieaitly targv*, and vlien injected into the 
nmSra of man a temporary inAnmmation reaulta. 
An aetiuil infedion of anj eort can not bo pro- 




dwwd m aaTvifilfl; the cctcd ar» kilM ulihout be- 
ing permitted to prohfcrnic-. The endotoxin (gnn- 
ntoxin) is fairly resistant to licst, being deairoyed 
only after proloQgetl eApuaui-e (o a leuip*!rature of 
100' c 

Til man lilt* miiptms memljrjinea »nd endntheLal 
aurfflces ere more sosccptible to infection than 
other tissues. The urechra of male ami ferttab at 
bU agts, the coiijiinutiva in the new-born, the 
TAfn^r^t utoruB anri tuboa nrc probably Ibe most 
ftisTpptiMp- Lghb Euateplible are the vagina in 
oilier AVQmeiif eepi-ciully ihusu whr* hav<* borne cliU- 
dron, the bladder anii, in n>:Tutl9. tho ccnjunotiva. 
Tt is remarkable tlmt there ure so few canea of 
gonorrheal ophthalmia in adults, conaideniig the 
opportunitiw for infection. Infection of the 
mouth. Tiohte and tear sai-s is extremely rare. Es- 
tcHi^ion from the nrottira to adjocei^t dtructurea 
take* filace either by niiy of the enrfacea, aa in 
iaiijlveiite^LL of Ihe prostate, epidid^-nib. glands of 
Barthohnf iiterun. tubes, ovjinte, peritoneum^ blad- 
der and kidneVB, or by wny of the lyinphatiri as in 
i&fections cf the periurethral tissue or cellular ti^ 
ffnoof thepelTiB. U:^Tni!ly infecttoaiof theblailder 
And kidney, ancl not inTreqiiently of Mir priWalr', 
Fallopian ti(bc« and pelvic tiA^ue arc of a mixed 
ehtracter (staphylcooocuB, strcptoeoecna)^ but not 
necwrorily ao. ArthritK tendovnginitiEi» cndoctr* 
ditfa, which vaually is ve^tativo l;ut may bo ulcer- 
ntiv, RTP Ihe more (!OTrLmon rneljLVl»lie e()mpli(^a- 
tions. Lets frequent nre fcricarditii, pleuntia, 
•Dbcutaneooa abei^ef^t?^ and iritte, Ae to whether 
the cotiULeoai plu-noniena KOirietir^es aeen are due 
to metaatflses or nrr of purely toxic origin sccmn to 
b« undetermined, The blood stream may he in- 



ricFECTroti jw> tuiivstrr. 



fcctcd t>y vMj of the Ijnapbolics or locaJ Uo«J 
TMScle (gonorrlmJ tbrombovis). 

TJie i^Qcnce of Uk eDoiEnoud ykmgocjriotis ol 
the cocci on the eourvc of j[Dnorrfi«« it unkDOWD. 
Silica the in^eato) roori uiiMtJIj hmxp « typic^ 
form and tt&l& irell, it would aeera tbfti tlwj mist 
Ukc action of th« IcTicooyiio fcrocati. LikoviM 
the nuck-i of Ihc leiicoc^irs iisuolly stain writ, 
bcopo thew is uo cvidcuoe ol a marked toxidtT 
of tb« oow: for tln>*t' cclU. Tho mfctiADJCftl im- 
prisoimiciil of iha or^aniams by the IcccocytOi 
may be of ioflvcnco in localitin^ tJie infoction. 

During the course of ^oiiorriien "there talus 
place a pronounced mctapfairb of the cpithelinin 
in uhidi the oylindneal ccUd are changed into i 
mort' cnlioidul mul uv^ri |)rivtitii!iit furm," Follow- 
ing this c^rijrc the ^nococci &re liixutod to the 
lurfioe of th« shared epitholitim and penetrato 
more deeply only tii the ileinilj of tlie fliuiil* anil 
Cryptj^. ''EvoTituitlly the ^norrhcol proc09 w 
Ijmifrd to siu'h ifinUM points nnd the gortmriim 
thereby cntefft into a chronic at«ge'' (ol)tier\4i1io» 
of Finger, cited by Nei*«jr nnd Scholts). 

Tlip conditions whiclt cJiiue the enWdenee of 
aeuF.o jconorrhca nnd vWayf it to persint at n chronic 
infection havo boeii tht cul>ject of mach epocula- 
tioo, unprodueiivf for the most pnit It i« not 
due to Q flecrOftM' in the vinilencc of the cocci 
finer th(nr onginiil inff^ticmcmw; is retained for 
others ; nor di^c? the local reeisUinee of the mucoun 
membrane reach a hi|?h point, ainee reinfection, 
or heller "an peri nfpc lion*' iu powihTe At any time. 
A man eufferinfr from ehronic gonorrhea and 
having infects his wife, may again bft infoctod 
by hifi ^fritc when lli^ fronorrhen of the latter Hm 


ooyocooovs serum, 


ttecomo subacute or chronic. It haa beea euggceted 
that the condition in chronic gonorrhea may be 
ont of "mutual hnbituctioD bclwten the mucous 
membrane And the gpnoooocus/' i, e.^ a habitiiution 
between this particular iuul-cjqh luenilraiie ani 
this particubr gonococci33. Beoauec of prolonged 
existence under unvarying conditions, the growth 
energ)' of the organism may have become leea. 
whereas, if it ie pUeed in a slightly diifereot mo- 
tlinm (irnnnfiTpnre tn another individuni), ita 
growth energy (abUitr to proliferate), becomca 
aupnentcd, and reiDfection of the original hoet 
u iih the wime strnin hecoroRS pnssiMe. 

Jt hoa ofton been noted that eal>sequont attacks 
ruD t milder course than the prlmflrj* infeclionj 
but aoflceptibilitj ia nlwars prcacnt, 

Ucc^ez, Calvjno, and also do Christmas have •"•■■Miiir- 
immunized with th*' roccns or toxic aabstflncea 
prepared from it- By growing the organism ia 
8«mm bouillon de Chrietma^ prepared a toxin, 
the toxicity of wtiich was tinted by intracerebral 
injcetiona in the guincfl-pig. Immnnization of 
the gninca'pig reenlt^d in a acnun with antitoxic 
properties. Corrohorniivc work hits not been pub* 
properticp. Torrev has nhowo that hv immtmiKP- 
tlon of nnimnU n acnim nmy ri>niUIy Ijo protlmvd 
wbicli contains specific bacleriolvBina, ag^luLininh, 
precipitins and complement detiation untihodieiL 
HnntiTtan nnd other* hnvo found that in gonor- 
rh^I v^Wovaci^^'i^ the <^psonLC index !» low En 
oariy ttw.ircE* and in ihow m whwh rrftiTprv flow 
not tfllip plnnr*. and hpmmm higher with rpcovprVr 

Torrey in 1906 prepared an antigonocrirciia J'^va*^?' 
t*Tum by immnnfKalior of nthbit*. Sinco that ■»<!*», 
lime, a number of different gemma have been pre- 



partd fmo «ur4i «niiRiU u iiorM« nnd mmK Ttiip 
Kporta coooeroiog Uio rdiie of a&tigoRocixr» 
fvmm hiTo Imvq ai yvt too vsried to admit of a 

Tic riiticittAncKtm inj<Hioi] or dpad ^oocxx^n 
for curatire purposes Ims twen apporvnllr of little 
value in irate urrtlinil Infrrti^inF. Tn diroafr 
tnfcctioii« of the Qtvthraf ppr:«tat« and ^emioa] vcn- 
dn wmn^ tatkfaelory r«aiilla Imw bc^^n obtaii»<d. 
Co!c ami Mirnkmm nitd Iron* find that the tin-ine 
tt^tin^t of jTonorrbeal arthritH is of rnlui; in 
loufnin^ the pain and fin ^hoHeiiiiif; the ronrM of 
the infection. 


n, cpn>Euic CEittBitosnyAL MESHNcms^ 

Acute inflammiition of tJie meningci ma_T be 
caused by a Dumber of ra]cro-<tTsaiusme: Micro- 
co/^a^ meninffiiidif. a!ai> callwi the Dipi<KOc<v$ 
iiitra^4Utiiarit memnsiti^i^^ or hrieily the meo* 
ingjOOOOCue; Oiptococcus pneumonia; Sirtptococ- 
cvs ptfoffenes; Stcph^lccocfus ptfcgantz; Bacillm 
inflnrntJF; tiariHuj jmrummiiir ; Haciliva tjfpho' 
tut; liaciilus £oH c^mniuai*; liacHias moXUi; B^ 
oiilus pcs^i. The firftt two of thia number, tbc 
meningococcue and the pneauiococcue, in addition 
to ciiEisjTii^ ipnrR(3b nitr-f, hIkl prorhuT more or 
leae extensive epiilemics of so-c^ll^d primary mea- 
tngilis. Tliat the pncumococcus maj alao «etifte 
mcningitii; Becoodarv to iineumof^occus inf^ioiu 
in othcT pflrie of Ih? txvK haa hrrn mt^nlioned. 
Alio ihe meningitis catised b/ the other pjo^oic 
ooeci usually U e^oondarv to tiome other auppura- 
tifO focus, oft«n tbe middle ear; that eauaed hy 
thv or^iivin* of typhoid, gfand^ns pla^^e and 

intxicma ccoire during \ht Dourse of the dUeasea 
cauBod by the correspondJng mioro-orgamema. 

Prviirja^ to IBS? diplococci resembling tlic pncu* Mic-mrp«ru 
mococcuB had bccD found in the exudate in caaca *"" " '""*' 
of cerebrovplnal menmgitia by FoA and BordoDi' 
UffrcduxKi, ]iy Fmenki^l and others. Weichsel- 
baum made aimilar obecrvationa during tho same 
y^flr, and in addition di^st'iibed six cuges iu which 
a diplococcus of another nature was present in 
pure culture. To tbo lal1«T he gave the name of 
JDipbcva'UJ intmr/iUitlnris mcninffiiidU. Exten- 
rirc observations by others, both in Europe and 
Americn (Coiindlmsn, Mollory and Wright, and 
oliicrs), revealed the pre?iencp cf Iht iBat-nnmed 
orKaniftm in mnny inslanccfi, and allowed that it i* 
tfce most mmmon rmise of epidemic cerebroflplnal 

Tho rauniugot^oconG re^mblcd the goiLOcoccoa 
ctowly hi that il 11^ n^ujklly foitud in btHnnit^a) taped 
IraiTe, nearly alvraya within pUE cells, ant) docit nor 
rtaln by Granf* tnt'thtvl (Weichselbftum), It ib 
properly to be call^ & microcoeocLs sjtice It divider 
in liro tianetcr^' direotjone (Albrci'ht nml (ihon) ; 
Ictroda, unall groups nnd sliort chafna nr^ ram?* 
tam«6 iten. However, it formfi no striking cliainji. 
ia non'motilc and prodtices no sporcA. Growtli 
may \w ohtHiticd cm some of the nrdinHiy m*dia 
(iflTccTin ognr), in which Uie or^faDiBni differs 
from the goaococcufl^ but a medium which oonlaini 
blood or xerum ik mtich m(>ri' fnvornble, It tB nn 
obligoto ocrobr. irfowe beet at the body tempera- 
ture and virulence is won loit under ftttifidal 

Il produces a nnrabrue on meat broth wltb vi«biii«f. 
doudirg at the navdliim. Viability U rviumed 



iSFSCTtoy Ayo iuuv^'trr. 


ofilv for a few dtjt at mom tomiMnttun. When 
dri«d Qti pftpcr Aud dpocod to the vunligtit it tft«» 
no longer Ibm t<r«nly-fonr bourv, in a dflrk room 
OTv«ii^4vo bonni iCoi^ttcstraan, ^[aliorv muJ 
Wri^t). It » killed br a tcmp«ralur« of'^A* C 
for thirty mtDUteE (Albr^ht and tihon). 

The aumiagaocMmu h» liltlp Hruknoo for ani- 
nuk> Whdt iojcctcd io sofficicnt qu&ali^ inU 
tilt p«ritoiMfll ^r pleural carli; of whit« xn»oe 
daUJi raKuha in from Iwimty^four to fortr-^'ght 
bours, but Dot wbaa given mWuiinoomBlj. Me&- 
i&gitts may be prodikMd bj n^dural injoctioiu. 
but ihjt discaae docs not rcMmbU tbe «pidflmie 
mtntn^tk of man. So far of ie known at prtsenl 
tlia i^rgaDtim do«< not produce a soluble toxin, but 
posJc^Mitf intltcr on CDdotodio. Attbon^i Uie difi- 
catd i(i iiFij«Uy fpokcm of as a primary tneaii^ntu, 
diert! k reodon t') tiolttive that it U «c«>nd!in- to in 
acute rhinitia or ncutc inflammation of tlie accvfr- 
vory aiDtiffoa or middl« onr, in many fnatanca. 
I'Vom tJiaae places tJw eua^u^ tiLur rm^ilj rv^irli thv 
mcai&goi by way of tho lymphntic cliaQD«bi or 
blood, Thft InKrr, nrcording to Elaer aiid Hun- 
toon, JB pin^balljr Uie uAual rout^. h tifl» l>rvn 
f<^um) r«pca1td]y in tho nowA of tho«* ai;^odat<d 
wiih friifipnM with Mip ^li^sHr: in qijoIt MMd an 
ocut« rhinitia ma) b* pre*cat without the Wibfe" 
quont dovelopmcnt of mcnirLjnttii- The clinical hb- 
1cr,v 8lifiwfi tliAi tlip infection commo»lv id pre<'«d«il 
by iicutc rhimtiK. Th^ inRammatioD in the tnnniri- 
f^t in nl^^nvft rerebro^foml in it^: difitrii^Titiin and 
ia diuriict^rixed by a purulent or fibriuo-purulent 
«xudnto in which the diplococci aro prceeet in 
Tarying qnaotitip-^ Ptti^osTc may oftfn be eitab- 
lUhcd dinicallj^ by the microicopic or cnltural 



<7iAmiti&tio[i of the c«r«l>rci«pinBL fiuld which ffl 
removed bj lumbar puncture. 

Acute encephalitis, acute bronchitis, lobar pncU' 
EnoEiiA find acute artjiritig have been observed as 
CO mpli catkins, in wbidi orgHnismft ivEpmbling the 
racuingv>co(jc*us have been found in a number ot 
instances. An ncivimpaGying Ijronchitiu, lobar or 
lobular pntumouia maj be ctused by mUed infec- 
tion with other r>rgaiiisms (pncumococeus, atrcpto- 
cncpuB, atnpbjplococciis). Sin^e it would hn difTS- 
cult to explain aomc of these com plica tionfl except 
on the liflsie of mctastasiEj it tcema very probable 
that tike organism renrhea the Idoml i^l.rpam. Micro- 
cccci resembling the nienmgoeoccuB have be«o 
fotnd in acute bronchitis, rhinitis, lobular pneu- 
monia an*J conjunctiviti^ in the abflcnce of cere* 
bral iDvolvomdntn ftnd it id possible that it may he 
Ihc cauae of iatlependeut inf^Arnamtions in these 
tiuncA. Wcichscibanm. however, is inclined lo 
doubt the identity of imch organisms with the 
m«iiTii;oe*HTiiB- Prti'titulurlj in creeq of brondii- 
tia and lobular pneumonm the coccus may be con- 
futed with the Micrococcus catarrkalU of Pfeiffer, 
witJi which it in JdeitUcai niorphoiogicaliy. 

The extent to which the incdiiigoeoceufl is u 
normnl inhnhitaut of the tinBal mnconis merabrare 
i« unkiiotfK. 

Since the orj^ttnism fieems to be excreted ehjeflv 
or only with the niisnl diwliarges, the latter prob- 
ably are important for tranEmiesion of the infec- 
tion. Becfluut of the low resistance of the organ- 
ism to desiccation and light, tran&niiHaiou prob- 
ably ii A fairly direct one. This le fluggosted also 
ty the occasional opeorrence of qiidemic* in inati- 
tutionan ContapoufliCAa is of a rather low order; 

(loBA anil 

■ n't C'tn- 


Ml 111 aB« 

thtt is indicted bj Ui« dutributioR of the 111 

Wii^t is 5o0toD» the dtt bein^ •omcwhat dil- 
fofirif iofwltd wrld wn- litUc trndf-ncy of the du- 
eoM lo occur In gniupi of indi7idual& ur in ^ereral 
nkcnbcn of a family. 

Ttn deEribititj of AtYiiJing rnoUrt inth tha^ 
infficted u crid-nit; »pKiaJ prophrbctic meft5* 
cm »re not IcDwriL In the pr«eDc« of an C]}i- 
drtnic tbn tnttlni^ut of rhinilU wilh Iiicjil ■tiliM-p* 
t»c» vdfild anient ilacir 

ObiMrcft and jooitg people an? [lanieiilarly me- 
>i?plibW to Wtb epidemic nnd upcrradic iiifoclxiai 
vith tbc nenm^oooociw. Expontrc inctdvnt to the 
cold and rariat^ wvaibcr of the winter and spring, 
in wbidi eruM'&f Ibc divevc pniaiU, majr bo in* 
AucDtial in lov^risg iwstscica- Socoad ottAcki 
srr rnrr, Cmutdlmaii, Mallury and Wrf^it col- 
lecting COJy fiTT tach cscamplcv from the }Jtcr«tnre. 
TJpicrre imnurtiMd animak witb culture an'l 
with ■ toxin, the latter being a ^jceriii extract uf 
nkl cokarc«. Tbeir reaiatancG to infection was 
Mid lo be inrtvaaeJp and the a?nim of highly im* 
muniicd aninala vas antitoxic, preTentlTC and 
CnratiTe for other animals. Conoborativo woHt 
ia laddng. Ant^rding Iq Havw, the wmm fn 
ei0QS of epidemic memogitis ahows an increases 
baeterievdal power for the coccu« on tho thirtoenth 
day of the dbcuse; tJie agi^Iiitinias whicJi develop 
probably perattl for scene time, but arc little abo^ 
NoriTia) hiimsB »criun » dirtinctiy bactericidal 
toward the vcttingoooocna. Tbia property m 
InertaMd in eera of mcningitii eaeea, and is dimtn* 
itbfd, bnl nnt eutirel^ d««troyvd^ by boating to 60* 
C. tf<T thirty minotw. Oerfbra>pina] fluir] act« in 
ninch the nmc woy as heated ^rum. Normal 

jfr.v/\'c;r?a ssifOM. 



cerohroHpinnl finiiJ Joes not cmibiiD op^nin for 

In IDOC. nniimenin^li? i*enim wns prcpnrH Jn ^ 
thip coHntry hy FlL'^m?i" and hi Cormatiy by Kolle 
jiikI WaMricntmnu siul -Torliinann, Tlie I'pport nf 
Kollc find WfljEflcrniflnn Wfla the firet to flppoor. H 
ivfls quickly followod by that of Jochmaor and 
Inter l\v Ui«l of Fle_Micr. 

Flcincr prcrnTffi hie ^mim ns follows: Hotma 
were inocnlaW tiihcutaneously with one-fourtli of 
.1 sheep'fl serum ngnr jlnnt rultuiv-of incninpococd 
whiHi hnd b^n Icillcd bj br'rttin^r to fiO' C. for 
lliirty ininiilert. Tlie flofli- wah 'Imiblei] rtt patli 
:<uhf:rqiirrnt injcHion nnlil nn nmount f^qunl to 
fouT tesJt'tiibe <?rowthfi ronld bo given at interval* 
i]f from five tn fievi'n ttays. Altemale iiijrt'tionH 
of liHn? orgfliiisma nnd nnlolywitt* nf organisms 
wert* tben jfiven f\t apven^dflv interrals, in inpfflns^ 
ing ilosiw nnlil larpe (luantilies were ^ivcu, TJie 
flfnim prcpnroil in this wny contains l*flctcTiol^Hc 
aTTiNocefitor«. rpsnnina, agglTttininc anil r^nmpl^ 
mcnf-tlsntinn nnlihodtpd, Tt Im* ah^ »n Antitoxic 
action on lotio ntit^lyzntc*; of m£*ninfioro«'i. 

Neefly all tiie nbnve-nnTfteil nntilmiliefl linve Wn *i»n"iii»<i 
n«c<l to prtimntc the thcrnpt'utic value of tbo 
wninit .lorl>Toir»n, and Kfiil<» nnd Wnrajf-rmnrin 
nMiiiinli'il Ml*' hlren^lh *>i Hu{m\rmn^i{'ik terum h> 
the pToloction nlTon+M rnioo and gmnen-pijra 
fl^ninet !ivi> moninporoccl. Th*> method in nngflti*- 
fnrlftry hrriins'- <jf tbi- diffrrenoi' of \irulence of 
variouH Ptroins cf im^nineocooH. JohEing ron- 
dmlea that tho eslimation of tho (dilution of the 
flpmm at wbioh ofiMnio nction \9 ntifl presi^nt glrcs 
iht bwl indication ns to thr Taltic of thf* Et»rnm. 
^Ait n drHuitt' nut] 4ui(ab\' r^lnndard of ^tr^n^tb 


■ iDisinniB dilation ftHK'ity of « 1 Co 6,000 difi>< 
tion of the antiscriBii u pmpoaed.*^ 

Plemcr And Joblin^ coflidadc from a tttidy of 
Ihr tpiDil fioid, thftt th« most important acdon 
of Lb« Kfuca dtpeode on baclvrlfflt-^it* :utJ 
inutMed pJitf^ocytfcc aHioD. 'lli^v j-nv th^ follow- 
inp tnrtfiMtinQf for thi^ um tvf tho livnin:] :* 

*^be AQtiMTtiin elioikid be kepi in a refnjrvniiDt 
ttQtil it U to bo tw^d, nlk«n U «bouId bo wnrmef 
to 11m bodt tuniprniturtt fH'fi^n> it » Injpcit^. 

"ThB wttueruQ) ia to b« introdu.«d dirertlj into 
the tpinkl tkntd tft«r xh*: vitlMlnwa) of cor«4»To- 
fpiMl Huid b; inr«n» of IttsiUr jninctnr?. 

'The qotntity of iotiwrmin to b« v«d at b ffin- 
gl« fnjMtlaEL ihoald not «ic««d for t)i« proamit 
ilO c.c. It i« d«0iraUe. although it would not 
tppmr «wcDttal. 1o vithdrav from th« spipal cttool 
it )Hvt w mnrh fluid lu Uic amount nf ahlifirrtim 
to be tnjctM- The injection should he nutde 
•lovk Kod carefully lo nrofd t1i« prodnction ot 
tym^lotat due lo im-rmnl pit<ai«Lin<. Tlitv pro* 
caution flbovild be cxcrdnd o^pcciallr «bCTc the 
<l!iAmitr of o«TObroiplDa1 fluid vithdr&wn ii Um 
(ban Che amount of aniiicntin lo hp injffct<d. 

*niie iDJfction of tho nntijcmm fbould be 
n^Mtfd artiT tveiitr-foiir lionre for t^ireo or four 
da>^ or Itmgrt- Whether nn>- advnntacr wit) be 
^[•infd by mon fr^uent or tnor? nnmermw iojcc- 
lioofi tbas h?ro fndifBl4^ a vidor fiirpeHeDcn miiat 
divide. As umeh as ISO c.c. of the nDtifcmni hare 
bevti inject4?d into the fplnal eanal !n four dar> 
withmit caiifiiug nnplpuvaiil KTirpUniiFi. 

Tlio CT'irlmre in<iicnt«i thot the rflrlicr in thr 
co«T«c of the dix*aw iht injoclions »r* nuido the 




!>pHer thp reaull*. IT&ncf, should lie dim pre[>- 
nratioit of the firal fluid obtntricd by ppbttl puuc- 
hire show Grflm-negdtii^ dipio*?oeci, *ome of which 
nre witliin Icucocjles. an injection hIiuuIi.! be made 
imnioJiotclj" and without waitiiig for the reauitA 
of culture iviri^. Sh(»uld the diagnosis he loft in 
doubt or tlie disease prove later lo be of anotber 
nature than epidernip mcninptie, no harm will be 
dofle bi the injfrtion of the nntisenim 

**AlU]ough the beet results bflrc thus for beon 
obtained wbero the anliEenim bus been injwted 
e«rK in the ili«e/ise, yet the spnnii ^honld be u^^ed 
in its later stnge^ nlsft wrtil our knowled^ gov- 
erning th? value of the serum be'-omoB more pr^ 
cise. Tlie iE]dieuti':>it& ut present are ibni: it U 
UAelc^ to employ the aerum in the vprr kte stnge* 
of the di»ea*c in nhich chrooic bjdPwepMtia h 
already derebped," 

Flexner and Joblinjr ooneludc from an Rnnlvflii 
of A Inrgp nnmbpr of repoTts nf th^ "**> of i>Titi» 
mcriintritiB senun, that the Herun ia of raltic in 
rodurinp the period of i11n(»Bfl and diminixhinjj tho 
fatalities dwe to tlie diftease. The figured nf Dunn 
show that in Ih* Boston Children's nospifal. the 
mortnlitv bofore th<» m*o of the eenim. from i\^ lo 
80 per tfnl.. wat- ri-dut'ed t<» below ISO pt-r cent, 
after the iiec of the eerum. 

Vatv* of 

biflucnzit occurs fporadically ond in q)id^Enic» 
of greatfti or lei^s proportions, hr. extreme eon- 
hi^ouineiis is «hr>wn by the striking tRpidity \i\i\\ 
which it aproad over tbe whole cirili^ed world in 
the epidemic of 1SS9 and 1890. leaving behind it 
a trail nf leuer epidemics which Imve prcTaitcii up 
tc the present time. 


iyncTiOK asd tMuuyirr. 



Daring the «pidcinio juM C3Ud 4 number of or- 
gtniAsu wtre errcncoiulj it«ccrib«d u the catue of 
tbe dunse. In It'&Z, I^vcrer, Pfci/Fer dieoovvrc<I 
A minuu baciltui wliicb he found consUatly AU^ 
in Isrg« numbpr; in iho Epiilnm of itifluonsn pt- 
tientd only. The oWrTfttions of Pfdfl^ liavc 
b««D cooflrmod by a Urgi^ nunsbet of iovcstigAton, 
■Dil tliu organism, thaiiu* wftvmia, » now ac> 
copied lu the caii£e of the <liM<AM. It ie ono of tbff 
Mnnlleit of bacleria [O.t or 0.3 bj- 0.5 roicrom), h 
noii*n;ot:lc «tiil fonn« x\o apor<^ A medium god- 
tifininj^ btnod or hemoglobin ie ttwntial for its 
nrtifjim] oiiIlivAlioTir aD<] I'teii Diuler Uie Wt txin- 
i]ition» it grow in<^gcr!y Jind «lowJy. A number 
of blood^^ but particularly thos^ of nam snd tho 
pi^iruii, ftifrir lis gruwlh. II is n ^l^mls iicrubv. 
llic orjfiiDLsiij in bc«t *liiiiicd by n dilute foiulion of 
csrbol-fi^chsin (I to 10). nr<). Hk« the plagii? 
.bacilhia, exhibits poloi aUiEUig, i. t.. the ends 
tlftin more deeply thnii tho (central portion. 

VMien th« ttaphylocoocuf nn^] #omo other organ- 
inm^ r\Tc gmym m miicil cuUurv willi th& influ- 
enza UcilluA, the lattjfr U ^ttmulatctl to mora 
vigomiu growth. Acconling to Jacobfiohn, killed 
cultiircfi of the fltrcptococeuA ^Tcallv iocreaae tlie 
virulence of the inAufn^ baeiULtu \vliQn the mix- 
lure U injecled iiilo HTtrmulA, 

rfdUor <lcAif:nalC8 a« pseud oicfiuciiEil bacilli ft 
number of infltieDza-lihc orgoninnt vMeh have 
Wu found ED mail and ariimaN, Thry hnre Uie 
EnorphoIojTT of the inliLionza baciJloe, are a little 
Iflr^er, anr! also prefer a medium vrhich oofttains 
htmo^clobin, but *irw jiomc of them occur in ani* 
mnla which are known not to be snsccptible lo in- 
fluensca, it ia coneliided thai they cun not be irlentf* 


cai with the infinciiMi bodllue. The tnflueDEfl-liko 
bacillua whlcli Joclimann iLni} Kr&u^ t^nsider &a 
Uic eauso i^f whcxipin^'cough, may be mentioned 

The rteiiiUin^e cf tlie laciltus ta i)e«icciitian, 
ftuniiglit and unfovornble temperatures ia very lov. 
It dies in ftfjm tweolj-four to Ihirty-sii houra At 
room tcmperalLirp, wljen coiiUin(.*d iti *putmn, and 
Uvea for aljoul thirty-t^'o tioura in hydrunt water 
(r/etff«T), It is not highly viruleoC for ADJmalfi, 
aiUioii^h ronditinn muI to resemble- influ- 
va£ii has litfpu produced m tnonkcya by placing 
jjiire ruhurefi on ihe na^iil iruicou* iiieriil»ri»m.'. 
Folal iniectiona rnoy be |jroJuccU by intra- 
Tenoiu inoculation of the badllus into monkeys 
fend rabbity and killed cultures produce a fatal 
mtoiicatioD in rabbits. Virulent cuItiLrcs in autli- 
cient ijuantitv produce frttnl pentoiiilifi in guinea- 
pi|^. 3incc th? bacilli acem not to proliferate 
when fatal quaotitiee are injwtecl intravenously 
inli> mbbibs am] nincc fntnl infoxivntion, withnut 
^e occurrence of bactcricmiu, may take place 
wiien a tracb^l infection is indueed in the ape 
(PfeiiTcr), it is amcltidcil thai tfuf to;cic phmum* 
Ota of infliicnzn arc duo to tho absorption of bac- 
terial toiins from tbt miicnis eurfaces. A Moluble 
toiin ban not bci'n oMained in oittiirc medio. Tbi? 
orj^niAm U a fncnltnlirct pus (>rodiiocr. 

So fwr iiM in known, the intlTu-imi hncilTufl w eic- 
Cfctcd only with the wcrclion? of tnfccttd &urfacft» 
h e.. from tlio upper ri?fcpiratory paftutseft, con- 
juni'tivjif vnr, i-ir, TJir brlii'f, mmmonly held, 
that the influt'iiza baciflua doc5 not tntcr the cir- 
culation probably i« «TToneon«. That metatlatio 
inffrclion h powiWc, by way of the lymph or blow! 


1b ■!» llAdf- 

nncTtax Axn iMMVNirif. 

dunacb, » thftnt by lh« oocurrcnce of mdiMm 
iiMaii^ilii. and, nnlj, of luJiiieDai peritooiUt 
(Hin i&d Tfadi), AoorOlo^ to Jeh]«, Uw infln- 
cnn biciUns inTndca tbc blood vcrr fr^uentEj io 
•ooke of thtf MuU exaiith«nul4. It vae fou&d in 
ibe blood in 2S o«t ol 46 ctt«v of ffarlift fcTcr, id 
15 of 23 COM* oi nituks, uul in £ of 9 caoes of 
tariodit (dtcd by Htkloen). EIciK«p then d»- 
csKo would seem to create coodttioiia f&Torablc fix 
^Tuioc bv thie bMilliu. When tbc bacilli rcacb 
thr blooi] tbry jmiliAbl^^ nrv killnl ijnirkt^. )t U 
probable titat tbc ordinary Dcrvooa pbcDonuflA of 
tbc dteote aic due to intoxicatioa nthcr than to 
actual infection of tho iirrvco« rtnicturt*. Aa to 
whether tbc symptottw of ao-cAllcd intcfltmal ia- 
flneDza are due to vx inTasion of the irttaatiMi 
hy Uie bncilli or to a ffpvcialiMd action of circn- 
iatiDg toxin ec&ms &o; to have boon dc^nitcJv «0C- 
tle^l^ Th«re cerloiDly ia altinclant opportunity for 
infection of Ihc intcattnca in caac* of bronchial 
infln^nxu. In Di« bronchitifi of influonia ihi> oi> 
puiisiiiB ftre fouQd iu largr? imiubefs in tlie unmller 
bronchial tube*, both frvc onrl within Icucocytce, 
hence» in warching for thp bacHli cHmcalLy \X 
thotiM W ctrtftin thai tlic sputnui cjLammt;i] rrprr- 
semts the bronchial cjcudalc. In tnfltK'nza pneu- 
monia, which iisnaTly is of the lohular ^pe, the 
liadlii, mixed crith pue ccll« aniil contained in 
thfEiii, arr found in hrf^ Dumbere io Ihf^ nJrtvili. 
1^1^c c^ilUtrc^ of th« bacillot hfiTo b«« obtain^ 
fnwi own of cunjunctiTitik, and they occur not 
lnfro)ucfi1ly in middle-cftr cnnipIicuUons ^hich 
d^^lop during t)\o courts of th^ r^innajv. Tnfln* 
VMM fnnjiinctintiii nmclipu^ rjci'uM n e]>idernic 
hmi\. |iank»lArly in inriitutions and EchooLo. 



mii»hr Iml' 

Pncumontc foci which tlevo ou durmjr inlluur;(ii mi*** 
lriH|iR'iitlj flioff inc pueuiuococcus, nml Kinjctimcj^ 
tht Btropioooccua i>r tlie bacillus of FheJlanUcr in 
iliililitioD to the inftuonza bncillijg^ anil fiimilni' 
mi\^il iufedion* wtof in pltni'lfj «nil in iniiMlif- 
c'cr rfii^nflos- Tnfluenun funy be foptnmpo»oi3 on 
otiier iT]f(*ctioTi8; intlmdtiale exiffering from pal- 
mohOTY lu1}tTrcu)o&is nre jmrLicuJarly suet^eptibk to 
iDfiuenEEU and iu them the proguoeia is imfuvor- 

TLe diaease is tranfiiaitleil directly from man Ui T™ni»ti»*i 
mfln and, chieily, it is erippoeed^ hy njeflns of lU- 
iect"?J droplets of jjputum winch are cxptjlleil in 
coughing m;d Gn?e«ing. ULviou&ly killing aiTorils 
opportumty for infection. Infection by indirect 
coniaf*t IB of 3p*s impoHflncf becmiap of tbe rapid 
death of the badlliij* after it laivcs the Ik^Ut. Imt 
lii'jD^ gGrrn? may well be {liBs^minnti^ by ^ikd 
hanJktrthiefs or other f;onI«iniiiat'"J lineu. Dust 
infection possibly h of minor conj^erinrcoo. Chronic 
inlliion;5a in wliic-h thi.> hHrtlli mjiy pprstst in ib*^ 
bronchi for week*, and cauec nrciirrtnt acute flt- 
facl{?. is of irnportanco for the maintenance of on 
eEiidemic, Iu tuhoTruloiia cnvitier He hadlli may 
floumh for Iohr penodi. 

Primary inf^fttrtn tnfcrs plnr*» in thp npppr TPs- 
pitory pfl6»ft^ca, and the diacaae eatcnile reaJily 
from one tnrfaee to another. a& from the nofe to 
th« pulmonary tissue. Infection of the tnr u>mil]j 
10 a comphcation of pharyu^eitl or pulmonary in- 
frrtion. (Wftnimiallv nn itiflin-oM cfnijunr^tivitis 
ie found without other loeaJization. '*Pnnian'" 
infection of other organs^ &i 1h« brajn and perito> 
neum, are melA^tatic. althf)nKh the originat foCii» 
or btrium mn\ not bo ohi^crsT"), 


ivFzcrioy axd iMMVyitr. 



UtUc or nothbig cttt bo dooo in the way of 
gPD^ral pTophjflaj(>«^ WflfiliiDg of th«» now tm^ 
Bkontij will] nntiscptictf during «n epidemic iil«} 
mMantly he praottctd, bat vith what ncc^es ii 
tmcerlsis. TL« aged and tbottu ol luw vitnlitt 
diould Avoid eipoisro to jnfuct^o, for in tli>cm Um 
serrrcr complicAtioiu> ndi tft pieuinoiuar an 
more likely to occur> When mfluecjcu conjuocti- 
vlEii appcara ^pid^niiodiT m tchoolfi, the latter 
«hmi1d Uj closed i^r xhv uif^ted childtvri «xclud«dH 
«mai.ii*, Althoii^b ]ittJt or nolliiii^ i« knotoa coixmiiugg 
iuT^'Iaa *'*'-' pf^^^"lit>' of a natural inamnnity in man, ci- 
|i<Tfcnpc t(«clit» tliat tie If.on llio urhole, irm icjm- 
ceptil>Ie, llie belief csproeeed by >oni« that nurv- 
log ohildren are I&m kUM:tjittb];r that^ oM«r people 
aeeniA 1o bart tcmt: ionvdaUGn, ulLbr>u^li tt i^ rrll 
known that they ure not entirely immirne. Infla- 
me ifl Bonietiinoa dUd iu an irfi'ction in wlikh 
one attack cr«aios a predi«po»Ltion for a Mcond. 
but the Irutb of thia i* doubted by many v)io liove 
tind uteniiivtT e^|ivrii-nc<' uith Iho diAi'HAr. Wnii- 
dorff, in a «tiidjr ^ tbt* epidemic wbtch prerailcd 
lu Cormany during 1>^t)]-£>?. fnv^d fii tht* ttnnW 
number of cajtdf, t.lie irre^lanty of tlicir dUtnbu* 
tion^ and c^ompartive exemption of rather iflrgf 
diatrirtji, rr^wmi fur Mipxiie^ IIiaI tir\p [illnnk con- 
Tort a di^ce of acquired immnnity; that ia to My, 
th9 population had been w thoroughly Icfeeled 
ilmiii;^ ffie jiifcftling _u^ar [>r (wn I.TviX oinij^ra- 
tivdy irw rcnminct] whn wen^ (iu*c>ej>tible. nllhoiijrh 
the disooi;^ \Ue\t nppt^or^d t<i ho more nmligrtnnt 
thmi in lb* tire\ioiJs year {cited from Beck), 
However, the *MnirK'nce rf wcfird ntlfickv shortlv 
flftcr thft fltst, and f»f r^patcd infi»otinn( in *Oflno 
individual* indi^lc (liaf acquired immunity i^ of 



short Juration. The nged, tboB« of \ov vitality, 
and tliD^ with {mltiioiinry tub?n;iiJoeiB, Jiuve low 
nwwtftnce to itifct^tion. 

Although Delius and Kclle were nble tp jirndiKrc 
A alight increase in the resiftm^ce of gatnea-pigB 
by the mtrap^riloneal inj(?ctioa of cultures, nf>lt> 
tog like a well-marked imniiuky was obuined; 
Dor did the acnim of immune animals or convalea- 
ptot mon show increased protective power for 
other anim&le. Slatm^ano, however* obtained 
WTum of eome proloctive value- for guinea-pigs, 
by the imranniKJition of rohbits nud gnmea-pigs^ 
hot it hod no curative effect. Tlie rcauite of Can- 
tani were eimilarj and buth olservers noted the de- 
vulcipmenl of tifltlericldal power, as determiued hy 
the PfeilTcr reaction, and of a^-gliitinintt. At pres- 
ent there eeemg littli; to hope frum vuroiantioriH 

There is said to be some iriLTeasr; in agglutinins 
in man lb a conaequcace of infection. The aggln- 
tinating power of tlie s^iuin of an immuniud ani- 
mal may be a» high as 1 to 500 (Cantani), 


nir. 80?T CHANCBE. 

Tlie independence of soft chancre and sypluiiif, 

and the infectioi^snees of the former by moculatiou 
with the pTinilent sfNTretmnB of the uti'drn, weri? 
catobliahf^d lon^ a^. iE»llet found thct Ultered 
pna lost ita infectioutJii^Ka. 

A large TiuTnl>i:r of obscr^eis had fountl bcctrrin jiBciUa* at 
of one kind or another in the pus and in etaincd "^"^■ 
tedioiiA of the walU nf the iilcpr^, anl probably 
tome of them («. jr., Unna), had aeen the bacillus 
which Dnorpy dt'srrrlM^d (1889) and loler puIU- 
Tated, and which i^ now proved to bs thn cnxtm of 
the di»eOEjt. The bacillus h very small (0,4x1-6 


«f«cr/o.v £.«U iMirnVXiTY. 

ttkrotu), \$ DOD*motile snd abav* piUr itaiiiiik; 
[t rtaemUfli tbe i^afiic bMiliua in torm, but i» 
KkinovhDt nnoUer, moA. dod« not ehov tbe «xU«- 
iivi' iriTokiliou form* of the latter. In the olcvr 
il lin AQgly, in leaaXi ietoqinl, or mon; HuirnH'^i- 
ticftllv ia die fofiu of bondtf^ mttlt up of two cr 
mor« partlld duiod. whkli iii6Jtrat4* the wall af 
tbe olcof. L«rg« nutnbcn we olttn foQnd in Uw 
polynorpliofkncltcT leiicnc^teA of tho poi, par- 
tk-uluil; Mt an «arl} fila^ of tJie teeuiu (Krwft- 
ing). Great cUflicuItv «V8 cntountcred id culti- 
nUng the bAcillu^, oikj Dikcrey'e ftr»t anocoes vae 
obtamed with * rn«diacn whkii eontJiiaed hamto 
ikin. li hoA sine« Wn ciillivotn^ on n^r tthich 
coDtainfl the blood or fcrum of tHAn, rabbit or 
do^ ijimmd itteicpltd to ciillivat« it in th« 
fr««h dcfit>rinat«d blood of the guiDea-|>%, bat 
was unanoocaaful bvcAuae the bacilli wetv phago- 
t>-timl by iht leuco^tu (Babw). 

All u1c«r rvaembUn^ that of tcft chaixre mar 
be |wodt>ocd in tb« ap«, and alao in the eat, by tbe 
inoeulatiott of pure cultttraa. Vl^ay TvioooiAaM 
man, aacceBsfallj^ from ih» ulrcrs of tbe cat 
VThen liTUig cuUurvs are iojecrtrd into tlie ^uIeio- 
[u^ (pcritoDPAl cavity, sabcutaneoiia tiefue, dura 
mat«r). tho bacilli an* quieldy taken up b>' leuco- 
^im and di^wted (Himmel). Hlmmel r^ru 
having ao docr»a«od Ehc mii^tuiic« of gujim^pigi 
h^ paritoaivfll mitv^iikiu of IhcIic add tl^nt tht!\ 
hmni^ »>c«|it)Ue to inrt^tion. After ivra or 
tbtvt pWMpv th« tultnrc bccnmr k> i'inile;Eit that 
fkM bMlfhcmia wna cauaod iritbout previonalT 
bVfTlBf tho mivtaDOc of th? animaU. 

rtilEDLAMiEn^ft fiAVILWa. 


111 man Uie iiafectton is tnLnsmitted to the in- 
guinal lympli glamls, h\ii never bocomee generaln 

One attack in man does not confer Itisting im- 
munit}'. S}iont»aeoiifi recovery occurs, but ite 
uiufie U not known- Inafaumch as the laciUi eie 
found within loucocytOfi, ptiogoc^ioeis may be ti 
fftctor in recovery. The teBdinera with which the 
atitoitioc Illation of adjacent stin takes place, even 
after the diacoeo hue caiBted for some time, Bug- 
gf^ts that genpral immnnilj is not established. 


The ijacillus of Fnedlamlev, or fiacUln/i Ttnew f-iBiHaiaafa 
tnonttt, la the tyjie of a rnthcr Iarij:c ^oiip of oac- 
trriH, rnllrnl thp FripdljiiiH^r group, or the gmup 
of Bacillus mucoius <:ajiiiulotua. In addition to 
the abiLty to producro a muoiii^ii(co capeuJe or en- 
velop, Ihey ha\e in gerteral the fcillowing diarac- 
terisUca (Abel) : short, plump rods^ varying in 
their propoTlinne. having n" mtition^ no fl«gd]«, 
tut apore foniiaiioo. and not Ht^iiiing by Graiu^s 
mothrKl. They form mocue-like maaeca ia cul- 
UiT^i da not lirjuefy gelatin &nd are facultative 
anaeroW. They are widely dislnbuted in naturet 
vnty from innocuouanoi^o to extreme path ogt^ni city 
IpT animnU. nre mrely found in the mt^uth, nose 
ftud bronchi normally (badlhfi of Fnedlaudcr), 
one type being a nf>nnal inhAbitnnt of the tnt«a- 
tinea, especially in children {B^ IticUs atrogencs)^ 
Pcrktna has ho(?n ahJc \iy clnaecfy the mcm^cre of 
this group in the hnsis of (hrir fermenting jwrniT" 
IciT lactose and Mccliaroe^. Hq found their nru- 
Icnco for nnimale. immunization and flgglullnatlon 
fntft, (no vaiiahlf |o gervt? its liase* f<>r rhiMJRca- 


ismcrioy ijfo tuMwtTY. 

tkn. 1b aita three awttben of thv groap — t^ 
ttttj be tlic iUM ocgtftinD or TAriationft of a tjp« 
— w of uUmt from tb« sUnclpoiDt of mf^^tiofi: 
BftctUiu of FriodUDdcr, Uw btdUtis of rhiooKle 
j^mm uhd the onena btcUItu. 

In 199 ttfcs of ftcalc inflAmmatiou nf Lhi:? }tiii£t, 
WddMiUitvm found ttie bftcilluB of pDciimcmij 
nitus tiiMf, twiee with «ttvptococd utd ooce vith 
tlw dipJococciu of pDcomoQiA. llw orgaAion 
oaoMs lobolar pikeumMila more frcqucoUj Lh«a 
kAar. Tin; h<»fi)i>geiiBciiu non-gmimUr ^rfno; 
tad tbc liTgc aiDOURt of fltdd of t rucid or laU' 
«ww eoiul»mc«. ar« cbameteTiitic Anatomic fett- 
urcK. The filvcoli conUtD nuuniTir numWrs of tbt 
badlli. The fc«cillu» of Friedlftndcr is fonod abo 
li Uie <^ii>e of pT^UtiK, cj«tltis, pyeloao|^ritu, 
MTotu or pumlaal periciirditii^ picuritis »&<! 
nningitiap which may bo accoiniMQivd bj braifi 
■tMCMw, Menipgltis wben produced by thin or- 
0i&kiai tsimlly or alvay« i« secondary to iafcctioD 
in oUmt pirts of tiw body by the same oiKanina 
(middfe ff«r aiu] ncuvaory Kiuii«(?i cif thn luvo). 

An 0iTftBt44n of the FVicdlondct type la fnind 
oith few esLO^ptions in tba tisffaei in rblnoad^ 
moiEi. and by aiduy ;» coasidered u tlie cause ol 
ihe MiDdition. A »imilflr oT^afii^m je found oon- 
(taBt^ in the BvcreHona and cmsts in otoui. 

.VatberuDu of ditlinct power hnre not htm otA 
taincd for menhete of the group. Prolonged ion- 
muiiatioa vith lOBto strains yields an agglutinat- 
ui^ aentm of lor vatTic. The agglutination re- 
action id of no vahx fo? identification of tfao dlf- 
fcrat TiM<mhi*n of t)ie jfronp. nor for dinioal 


ORQVP rr- 

Tnfectioi:s diaease* which iisuaUj are chronic. 
biit may nin acute eourees. They are chiiracteriaed 
by taflrk^d local lissue chntigea, which ciert a lim* 
itmg influence on the processeB. arid include tlio 
tnfuctioua prajjubninta, excepting fi3-philis, Tnfeo- 
tion pro'hiocft little or no immuniij, Tn some iu- 
stances the prolong jmmuniiation of flnimflls in- 
-dacM increased re^Latuncs to Infection (tubercolo- 
el») ; in other instancee thia \iAb not been deter- 
mined, or is dithoult of detcnmnation because of 
ttio ni>Q'Hi6ct'ptihilit_v «t Ihu nniiniils uwtd to 
the corresponding inferrticns. The serums of tm- 
mtinlAcd animala^ id sd far as this aubjeet ha^ heen 
xt\\tmtAgaim\r show little nr oo protective or cura- 
tive power. 


Klemke, in 18J3, bwt more pflrtieulaHj Ville- 
min, tn 1SC5, demonatrnted the infectiou»ineM of 
tuberculosis hy nnimal experimental nnd the99 re- 
sults were eul^lantialcd latter h> auch javeatigatorK 
ns. KfcbSt Chnuvciiti, Bnun^nrtpn And Colirlicim. 
Banmgarlcii firit ^aw the Cubcrde bacitluB in eeo- 
tjons of tubereuloua mAt4>rial frona whic)] the tia- 
fvc cells had becQ dissolved by potassium hyJroxid, 
and at almost the same timo Kocli succeeded m 
[l&nionotrafliig its presence in all luberenlou* 
Imioiib hy a special staining methocl. He eventu- 
ally obtained the orgoniam in pure caltures with 


i5TC(T/0y IXD tMMVA'ITr. 

1 fmnu'lvv*** 
f||k* nt til* 

which be tf^hx prodneed tnbercoJoBii is cxprj 

T^ie tubrtcl^ tiac^lhts it tin obti^tte aerobic pa»1 
iit«, bai tfao form of a deadet, tio&<fla0dlatod rodJ 
oftftn «1ighU/ curttd, from 2 fa 4 tnirraas Irirv;' 
imd frmn 0^ to 0.5 EWicroos bro^d. In •Uioed aaj 
flTOi in uDttaioed spccim«Uj wboB ptop«rJr 
iT^fatedr ft nunibef of spherical, otbI or cloagstH 
c\t*r spaco ctD U seen whidt Kocb «t om tine 
Uicujcht to be iporct. 'lltcy aro now oodviden-l 
either an xncartln^ ^r u raprfffintlpg foinp Ibrm of 
dcgemirdtion or rtecrrc avtritiotts natcfiiJ- Spor« 
foimatiOD la imccrtaiD. Tbc orgftokm U «up- 
poicd to poneaw a in«nibTBiic wbich majr be n- 
tpooftiUlo for iU ttrong Todftancc tgtisAt h^At isd 
(Icsicmlioti. Fcinb«Tg «pwkn of n nijclem ( f) which 
tnajr be domointntod bf o modified Borauunnk^ 
itaio. The orgtoUm iliowi numjr varittioiu in iu 
morphology under different oooditjons. It often 
«n0t« in isolated clcmpv, either in ctiJtaroa or in 
tiuuesp &Dil ma^ be excreted sa audi in tlve urioehi 
In certain cQl»rc» and aoniietixnca in auii