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OF LICE AND MENBy G. B. :MATHEWS

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In r6C4lnt mOllth.!, typhlUl has claimw fA,'idupread aUerniOtl. News reportsJrom Europe ha"'e mentWmd that 1M German amlUB in Poland mid Russia, terri·Ioriu notoriously inJutW wWi typhus, have kepi this scourge weU unde1' control bynew methods oj diagnom and prophllla:ri8. Here in Shanghai there have aUo beena number of typhus 008U which have come kJ the notiu oj the public, thus increasingthe interest itl prophylactic measuru.

There are several i1t8titution8 in EMt Asia occupied wi4h lIIe prepara4ion ojt'yphus vaccine. Among lhem, Ihe Fu Jen UniverBity oj Peking can probably claimthe longe.,t experiellce and moat a£CUrate IItatinicB oj the efficiency of the vaccine, sinceit hus been preparill{/ it for more than a decade.

The (mthor was bam in Germany. He studied philosophy and naturalllCiencesat St. AU{lu8tin near Bonn, as u'ell a8 in Chi,cago. Rome, and HG'NJ<Jrd; and lIIeologyin Rome. Later on. he undertook special sttulic.9 at the ZooloUical Seatio'tl at Naples,at the Robert Koch institute in Berlin, uith Hans Zi1l8.Ycr. the great typhu8authority oj Harvard Medical School, and with Il. R. Cox at the Rocky j'<'autltainLaboratory oj the US P11blic Health Service. Since i934 he has bcen Professor ofGeneral Biology, Pla,nt Pathology, and Paleobota'lIy_at the Fu J en U"ivcra-ily ojPel";ng.-K.M.

I N 1528 the army of Charles V wasbesieged at Naples by the Frenchunder Francis I. The battle was to

decide the struggle for hegemony inEurope between the two rulers. Charles'army, reduced to less than 11,000 men,was encircled by the French, some 28,000strong. The situation seemed hopelessfor the besieged, unt.il the French hadto raise the sicge. Their 28,000 menhad dwindled to 4,000, who could easilybe disposed of, and in 1530 Cha,rles wascrowned ruler of the Holy Roman Empire.Typhus had been his biggest aid in ob­taining the throne. This was one of theearliest and, at the same time, mosteffective strokes dealt by typhus thathistory records.

In 1566, Emperor Maximilian II with80,000 men set out to battle Sultan

Soliman in Hungary. Disease, undoubt­edly typhus, ravaged his army to sucha degree that he was forced to give uphis campaign against the Turks. In1632, King Gustavus Adolphus of Swedenhad to raise the siege of Nurembergowing to a typhus epidemic among hissoldiers. Instances abound in historywhere typhus held the tnlffip card inpolitical affairs. It is still a powerfulfactor in our own century. In 1915,typhus broke out in Serbia, and in lessthan SLX months 150,000 soldiers died,among them some 30,000 Austrian prison­ers of war. The mortality rate of thisepidemic was about 60. to 70 per cent.According to Tarrn.ssowitch's estimate,there were 30 million cases of typhus and3 million deaths in European Russiaalone betweeu 1917 and 1923. The Ser­bian and R.ussian epidemics show beyond

228 THE XXth CE~TURY

Ii doubt that typhu' has not lost itsvitality and power since it laid low thearmy of Francis I in 1528. Here inChina, where typhus statistics amongforeign missionaries are accurate, themortality mte is staggering.

CATClllliG TYPHUS

But how does one get typhu? Firstof all typhus should be distinguishedfrOID typhoid fever. The latter is essen­tially an intestinal disease due to Bac­terium typhi. Typhus belongs to theRickettsial di8038es. and the realm ofits work is the blood system, especiallythe smlill capillaric, and the nervou!!system. It is due to the presence ofRickettsia prowazeki, a microbe whosecitizenship in tho animal or plant king­dom is still an open question. The agentis caUed Rickellsia prowaul.:i after H. T.Ricketts and S. von Prowazck, both ofwhom died \rictims to tho disca e the."tricd to liquidate. T1.lis tin~' lnicrobocnters tho hUlI1lLII body through the biteof H. typhus-infcctod louso. The diseasemuy also ue call ,ht when infected,crushed lie -material or fece of infectedli e come into contact with delicateti 'ues llch 8.8 mucou membrane. Boththe body louse and the head louse maybe carriers. A single bite of a louse maysuffice to inject 50 many microbes intothe human organism that the bodycannot immcdiately neutmlize the ill­vaders. A battlc ensue., fever foUowsand, if the heart 'fLU staud it, thc microbesare conquerad.

Typhus is a,1I acute fever which doesnot alway conform to the conventionalmanner of fevers. It.s usual behavior isa foUows. After a ten- to fifteen-dayperiod of ineubation, the disease breaksout. Thc onsot may bo gmdual orextremely abrupt. closely 1'0 ombling aheavy cold or influenzf. The tempera­ture rises to 39 or 40 degree contigrade(103 or 104 degrees Fahr nheit). Thepatient complains of chills, great depres­sion, weakness, and pains in the headand limbs. Eruptions appear on thefourth or fifth day after the onset andlast for five to seven days. sometimeseven longer. When there is no epidemic,

the diagnosis i very difficult in the pre­eruptive stage. The rash usually breaksout on the houlders, spreads over thebody, and extends to the hands and feet.The spots (petechiae) do not, as a rule,spread over the face and forehead. Atfirst they are pink, then tum to purplish.and finally become reddish-brown andbrown. In the latter stages, the spotsdo not lose their color undor pressure.The names of the disease were takenfrom these petechiae: Tabardifllio y pU7I1Q8,De 1'01'0, 11)74; Febri8 quam lenticulas velpuncticulas t·ocalll. Fra~astorills, 1546;Piet,'re e:rmlillimatiqlle; spotted fe\Ter;Flecktyplw8. :\ SC\Tere headache is a.symptom of considerable importance.The typhus crisis sets in between thothirtl'enth and fifteenth day.

Since it is not easy to diagnose typhus,the inexperienced ma) easily mistake itfor another d' e "0. Without the rashand the epid mic, many a typhus easegoes unrecognized. Besides, there arefew places where the only safe diagnosis,that by mieroagglutination, can be made.

METHODS OF CO:\IBAT

Many attempt have boon made allover the world to combat this dreadfuldisease, oither by preventing its outbreakin ca e of an unnoticed infection (pro­phylactic) or by curing the patient byadministering a typical medicine (thera­poutic). Experiments made with the~erllm from convalescent patients orfrom immunized animals ean bo inter­preted as helpful or useless as the specialconditions a1'o interpreted. All the pro­phylactic methods have tho samo aim:to stimuJato the production of a.ntigcnsby an artificial di. ease on a small scale.Several method have beon tried out,and their inventors have claimed a moreor le:-. absolute protection against typhus.There are two currents of thought rol­ative to tho production of immunity:one group uses the living viru' the otherthe dead virus for injections.

I.IVINO "RICKETTSL~" INJEOTIONS

There are two Illain types of typhu'.The first is tho murine typhu , sometimescalled "Moxican" or "Manchurian ty-

OF LICE _um liEN

phU8," caused by Rickett8ia tn008eri withthe rat-fiea-man cycle, hence often called"fiea-bome typhus." The second is theclassical typhus, also caUed "Europeantyphus," caused by Riclct.t18ia prowa%~ki

with the louse-man cycle, hence oftencalled "louse-borne typhus."

In North Africa, injections were oc­casionally made with subinlective dosesof living virus. This is an extremelydangeroU8 procedure, since the amountof virus cannot be determined accurateIv,and the infective material may lead toan outbreak of the disease. So anothermethod was employed. The virulence ofthe living virus was weakened by addingegg yolk and olive oil to the infectiveemulsion. However, this type of injec­tion cannot be recommended, since theegg yolk and the olive-oil emulsion maykill the virus, in which case either thenumbel' of virus will not be sufficientto guarantee the desired effect, or the in­fective material will remain in the body.One instance will show the errors thatcan be made: in South America, 800persons were vaccinated against murUletyphus with the living, weakened virusaccording to the Blanc method, a mcthodgenerally used among the natives ofMoroc­co. Twenty-three per cent of the 800people became siok of typhus, and fiveof them even died.

Although only a very small amount ofRidelt8iae is required in the use of livingvirus, it is much better, and perhaps itis the only safe method, to use deadmicrobes in the form of a vaccine. Rocha­Lima was the first to experiment withthe infected intestines of lice asa prophylactic vaccine. After theGreat War, Weigl developed in Lembergthe method which bears his name. Hemade eystema,tic and successful researchesin the preparation of a vaccine fromiDfected lice. When the Polish Govern­ment stopped financing his experiments,he .A11 forced to stop his research. ButwheDeVer anyone approached Weigl aboutthe prOduction of the vaccine, he con­ducted the operations and gave a. visualdemOD8tration as to how the vaccinecould be. produced. This W88 very wise,

since everyone knows from experiencethe difference between reading a cookbookrecipe and then applying the di.rectionssuccessfully. The Weigl method has alsobeen used in China and Ethiopia.

FU JEN'S "LOUSE D1STITUTE"

How, then, L'5 this vaccine prepared 1Let us go to the Microbiological Instituteat the Fu Jen University in Peking andobserve the various stages in its prep­aration. The Microbiological Institutehas heen prepa,ring the Weigl typhusvaccine for the last twelve yeaNl.

At Fu Jen we use the Weigl methodand the Cox method. For the Weiglmethod, a largo number of lice and alarge number of Rickettsiae are required.It is tnle that the yirus grows in manymammals, but ill mammals the Hicl.:ells'iaecannot be stained, which means thatthey can be neither seen nor counted asis necessary for standardizing the vaccine.Thus we need a large number of licewhich must be free of other diseases,such as trench fever, relapsing fever,and Yolhynian fever.

A l.OUSY STORY

Let us start with the preparation. Assoon as we can diagnose that l~ persOll

has classical typhus, we know that theRickett8iae prowazeki are in his organismand blood serum. We therefore take So

few ellhic centimeters of his infected

blood (Fig. I) and inject it intraperi­toneally into a guinea pig (Fig. 2). This

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technicians elm administer about 250enemaa in an bour without a single miss.

With each injection, millions of man­borne, guinea-pig-reared virus are tram­ferred to a new h08t. TheB~are extremely small, measUllial 0.0008by 0.0004 millimeters. Here they settledown and thrive in the cells lining thestomaoh and intestinal walls and appearin large numbers in the feces. In a fewdays, the number of Riclcettsia.e increasestremendously, and from eight to ten daysafter the injection the louse would suc­cumb to typhus. From this fact it isclear that, from the point of view of thehistory of typhus, the louse is not thenatural h08t of typhus but that the louseca.ught the microbes relatively recently.In another thousand years or 80, theRiclet.U8'ilu prowaua may be absolutelyharmless for lice, just aaB~ roe1a4.limae has already become.

BIOGRAPHY OF A. LOUSE

You will naturally wonder: how do wemanage to get all the lice necessary forthe production of the vaccine? How dowe feed them, since their natural food ishuman blood? We have in the Micro­biological Institute our own stock of lice.They are securely kept in small woodenboX08, one aide of which consists of afine silk screen. There are about twohundred lice in each box. For feeding,they tl90 the silk side of the box (Pig. 6)

•'rHE XXth CE~7URYJSO

}o"ig. 3

aseptically, while the other remains areburned at onee. The small portion ofthe brain is then pulverized and dissolvedin saline solution for further use.

Now the lice enter upon the scene.The brain emulsion with the livingBic1ce.U8i<u is injected into each louse intra­rectally. Since the louse is only aboutfour millimeters long, this enema has tobe given under a binocular miC1'08C0pe,whioh not only enlarges the appearanceof the loUIe but also gives a plaatic viewof the tiny animal (Figs. 4 & 10). Our

guinea pig is then isolated and its tem­perature taken regularly. It soon showssigns of the disease, and when it registersa high temperature, from 102 degreesFahrenheit normal to 106 degrees, weknow that the fever is at ita height,which happens anywhere from three totwenty days after the infection. Theguinea pig is very suitable for our pur­pose because, when it getoS typhus, tbeBickdUiae multiply in all its org&D8,especially in the brain, which show his­tological l08ions. The fever is a sign ofthe fight between the organism and theinvaders. At the height of the fever,the guinea pig is anesthetized, and aportion of the brain (Fig. 3) is taken out

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ENIURYMEN AGAINST TYPHUS

F,,:. III. ~Iall' (al'''I,,) alld f"flla],' (la·IIIII·)1,0.1.1' 11IU";I' Ilndl'r tht' lIIil'r",w0I'('. ;\nf('the "thllmb" -like oppo"ible inner dawwh ieh ena bles the louse to get a good

grip on hairs and fibers

FIG, 11. One ,,·ea.r's guarantee again.:t dc'at h from (yphll.";:)1jrrobiological Instituto of the Fu Jen L'ni"crsity giving

Or. I>../. Tdlang uf theIt typhus.vaccine injection

OF LICE AND lIEN

and lay their eggs on a small felt pad(Fig. 7). Every day the felt pad istaken out. Thus from our hundredboxes we col1oot these pads and starta new box of lice, all with the samebirthday.

After four or five days at body tem­perature the eggs hatch. H the tem­perature is lower, the eggs may nothatch for more than a month. In hatch­ing out, the larva sho'WB an extraordinary&eDle of engineering. First it opens alittle lid at the end of the egg. But theopening is too emall for it to orawl out;it must squeeze iteelf out. How does itdo this' It swallow air in front andejecta it from behiDd. FiDally the air­pftlllU1'8 at the reM' is strong enough topop it put into a new phase of its life.Now it feeda, or sucks, until ita birthdaygarment beoomes too tight, and it changesto a new one, molting. This happeust·hree times. After the third molting,i.e., after two weeks, the louse becomessexually mature. The female soon beginsto lay eggs, about five every day, andcontinues to do so for about a month.This means that she produoes about 150eggs in her span of life. In laying theeggs, the mother louse fastens them witha stioky cement to hair or to the fibersof clothes or felt pads.

The lice, whether almost transparentyounptera or gray adulta, have no troublefiDding their nutrition if they are on ahost. They sink their hollow stylet intothe tender human skin, pierce a vein,and suck the blood until they are gorged.Some saliva flows into the tiny borehole,and if the saliva contains some Rickdtaitu,88 may be the oaee in an infected louse,one bite may be sufficient to cause af~ta1 eioknese. From this you may won­der how we manage to feed our severalthoUMDda of small guest-s.

At about this stage in our sight-eeeingt-our of the lrfiorobiological Institute, ourvisitors begin to feel itchy and are ob­seeeed with the fear that perhaps theyhaft beoome inYohmtary hoets to a fewstray Hoe. Our 10lUle doctor, D. J.TchaDg, who prepares the vaccine, has

not been vaociDated for more than twoyears and, though he spends severalhours in the laboratory every day, he hasnever been ill with typhus. Dr. Tchaogconfidently assures visitors that there isno danger of infection from a stray lousein the laboratory.

But what do the lice eat, and howare they fed1 We are lucky. ODe ofthe four assistants tells us that it islunch time for the lice. He goes to theincubator, which is always kept at bodytemperature, and takes out all the boxeswith their inmates. The boxes are eecure­ly closed. These boxes are then strapped.to the legs of human wet nurses (Fig. 8).They remain there for about twentyminutes, during which time the lice sinktheir proboeoee through the silk side· ofthe box into a vein and suck blood. Itis quite olear that the wet nuraes m1J8thave had typhus before, or that theymust have been vaccinated,' and thatthey must not harbor other miorobes, ordisease germs. That is easily determiDedin our laboratory. Our lice are quitearistocratio. Theirapartments arecleanedevery day and heated to body tem­perature; they (the lice) are eerved twofull meals of fresh, healthy human blooda day. It may be lousy busine88, but itis worth while.

'.l'HE UTILITY OF LIOE

After eight days of this high life, thelice are killed. The laboratory assistants,like undertakers, remove their entrails,intestines, stomach, and eeophagua, allof whioh are studded with billions ofRickdtaiae. This prooesa is done underthe microeoope. The parts extracted aresterilized with carbolic acid. Several hun­dreds of the digestive tracts are thenpulverized, the larger remnants of t!aintestinal walls being removed bycentrifuging. A microeoopioal teet de­termines the number of B~;a physiological test aeoertaiDa thevirulence of this particular lot of iutes­tines.

After this, the material is prepared forthe ampules, a set of three (Fig. 12). The

234 THE XXt,h CENTURY

Fig. 12

first shot should containthe intestines of seven lice, I :the second that of fourteen, I _ ...!and the third that of 'I! 'twenty-one- altogether ; ;about forty or fifty intes- 1. _,.. ;tines. The ampules are I

then ready for anyone who I :wants the shots. Who are I ~ ithe people who want this I' \ "'I::~cin~1r~~ ~!\II:place, mis- : ~ ; ,l

lL!/,,!sionaries - ',-' "',1 I 'a~d physi- - :~ _ ~ \, ._ \j~~ I ,;Clans who, .-. . .',. I

by natureof their oc­cupations,often come in contact with patient.ssufiering or dying from typhus. Theyhave to be vaccinated every year (Fig. II).

VALUE OF PROPHYLACTIC YACCINATION

The value of prophylactic vaccinationcan best bc judged from facts. In Po­land, 2,755 persons received the tripleinjection up to 1933. The results werecarefully tabulated. Not one person gottyphus, though physicians and employeesof hospitals were constantly exposed toinfection. An interesting incident hap­pened in Weigl's laboratory, which, thoughunintentional, was of value. One of themale wet nurses of the lice let his wifefeed the infected lice. His wife hadbeen vaccinated in 1930; this incidenttook place in October 1931. She wasimmediately forbidden to continue thefeeding. Howover, no aftereffects werenoticed. Vaccination had prevented herfrom contracting typhus.

STATISTICS IN CHINA

The statistics for China, compiled bythe Rev. J. Rutten are most satisfa-ctory.The Scheut Fathers, whose SuperiorGeneral Father Rutten was, have adifficult mission territory in North Chinaand maintain a personnel of 165 to 220missionaries. In the period of twenty­five years from 1905 to 1930, there were130 deaths in their mission district. Outof these 130 missionaries, 88 died of

typhus. Of these 88, 47 had not I'eachedthe age of thirty-six and only 6 wereover fifty. In 1930, Father Rutten madevaccination compulsory for his mission­aries in that district and established theMicrobiological Institute in Peking. Dur­ing the ten years from 1930 to 1940, nota single missionary died of typhus; theyhad all been vaccinated. The number ofdeaths occurring in the years 1931 to1935 was 7, a mortality rate that is notsurprising. From 1936 to 1940, 18 deathsoccurred; out of these 5 were over seventyyears of age, one being eighty-six andanother eighty-eight; 7 were over fifty;3 were under thirty-six (one of themhaving been murdered). Thus, during a.period of twelve years, when vaccinationwas obligatory, no deaths were due totyphus. This warrants the conclusionthat the vaccine gives one-hundred-per­cent immlmity against typhus. Somemight argue that better hygienic condi­tions removed the danger of typhus.This is not the case. Several of themissionaries contracted typhus during thelast twelve years, but owing to the vac­cination the disease was never fatal.

Statistics on the va-ccinations madeamong the Chinese do not, in my opinion,warrant any conclusions concerning theusefulness of this or that vaccine againsttyphus. The Chinese may, without know­ing it, have survived a benign case oftyphus in childhood. It is also possiblethat their genetic constitution is differentfrom that of foreigners. From historywe know that foreign armies and ex­plorers were laid low by diseases to whichindigenous people were not susceptible.

OTHER METHODS OF VACOINE

PREPARATION

'Ve may also mention some othermethods of vaccine preparation fromdead virus. Zinsser and his co-workersprepared vaccine against murine typhusfrom rats and mice. Another methodconsists of growing the RiclceU.siae intissue cultures on agar-agar. Cox recent­ly developed a method by growingRickettsia~of the Rocky Mountain spottedfever in chicken eggs. At Fu Jen we

OF LlCF. .um MEN 236

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tried this methodfor RickdUiae pro­tDdUl.-i and discov­ered that theRickett8iae grew inlarge numbers inthe embryo-sacmembrane. On anaverage, one eggyielded from ten tofifteen d0888, i.e.,forty -five injec­tioDs. One egg was so prolific inRickettBiae that it yielded eighty-fivedoses of vaccine. This method is nowused exclusively in the Chemotherapeu­tical Institute of Frankfurt am Main.

We have seen that typhus can bechained, and the aim of the variousgovernments of the world should be tolocalize the endemic centers 8S much as

qj6e '1leuro.suNjtl,On

possible. This mustgo hand in hand\\"ith hygienic im­provements, Le.,the eradication oflice. It Viill prob­ably be some timebefore, in somecountries, bathingis not consideredrevolutionary, thechanging of clothes

in winter time becomes frequent andregular, and a bathtub is found in everyhome. On the other hand, however, weknow the enemy, we know his malicioustaetics. \Ve can successfully forge theweapons by which we hope to conquertyphus until the time comes whenmankind lmows typhus only fromhistory.

, .

Working like linem n on a far.Bwlg telt'pltone network. urgoons uowoperate on the nervous system itself---<luring, delil'ute. miraculously effectivosurgery-to check the pain of incurablo disease or block the effects of hiddonilia that cannot be treated at their source. Pain of incurable disel1B8 call besuch unendiDa, UD*rable torture tJ18t victims look iorwanJ to deatlt formerciful relief. Doetora ueed to administer drugs which interrupt tlte agon)'witb .pells of lltupor.

Today the neurosurgeon declares that victims of inourable disease canlivo out their daY8 without drugs or 8ufJering. Every pain impulse, whereverit originates, mUllt. traveJ up the main 8pinal trunldine to the brain. When thepain cannot be eliminated at. the llOu.t"OO, the 8lIrgeon offers his recourse: inter·nlpt the pathway of pain. 'Thi8 operat.ion is performed at. the point just beforetho nerves of tlle painful part enter t.he spinal column. OnJy. small incisioni~ mado in tho nerve cable and great care must be taken to cut only the sensor)'llerve and not tho motor nerve. The patient is deprived of nothing but his BeMaof, pain and temperature ill that part of the body. His tactile lIense. or feeling,is left whole. Thou88.nds of tlll!$e pain,conquering operations ha\' already beenperformed succe full)-.