The following story is that of aprolific and savage killer, yellow fe-ver, and the events by which the veilof this terrible scourge was lifted.Some of the heroes' names will befamiliar but most will not. The storycontains three parts: first, a briefhistory of yellow fever and its impacton society; second, the experi-ments done in Cuba which eluci-dated the mode of transmission ofthis disease; and finally, the lives oftwo young men and their heroic rolesin one of the great medical discov-eries of our time.

Brief History of YellowFever

We believe that yellow feveroriginated in Africa and made its firstvisit to the New World in the late 16or early 17" century. For the next300 years or so, "yellow jack"ravaged hundreds of cities inNorth America from Texas toMassachusetts as well as theGreat Mississippi Valley. Eachwave of pestilence was markedby economic shamble, humanpanic and fear, and widespreaddeath.

From 1668 to 1893 therewere 135 major epidemics inport cities of the U.S. In 1793,yellow fever claimed one of ev-

ery ten Philadelphians, a total of4,000 dead. New Orleans, a fre-quent victim of attack, suffered29,000 cases and over 8,000 deadin 1853. During the summer of f 878,a huge epidemic shattered the U.S.:132 towns affected; 75,000 cases;16,000 deaths; and a cost of over$100 million dollars!

14 Winter 1996,

Medical authorities of the day ar-gued overthe mode oftransmission.Some, such as Dr. Benjamin Rushof Philadelphia, believed that yellowfever was spread by miasmatic (poi-soned) air. Others felt the diseasewas spread by fomites; that is, ar-ticles such as bedding or clothingthat were believed to be contami-nated. Preventive measures in-cluded cigar smoking by womenand children, and massive burningof suspect items.

The Situation in Cuba

At the end ofthe Spanish-Ameri-can War in 1898, Cuba was givento the United States by Spain. Andwhat a deal it was! In Havana, deadanimals were lying in the streets, ty-phoid fever was lurking everywhere,and yellow fever was always a

threat. During the war, 2,450 Ameri-cans had died in Cuba; 385 in battleand the rest from disease.

In early 1900, a severe outbreakofyellow fever in Havana killed manyArmy officers who were sent thereafter the war. The wife of one officer

took her own life after her husband'sunexpected demise.

The Surgeon General at the timewas George Miller Sternberg whowas considered the leading experton yellow fever. Through his effortsand with his blessing, Special Or-der No. 122 from the Secretary ofWar was issued on May 24% 1900.This order established a Board forthe purpose of pursuing scientificinvestigations with reference to theacute infectious diseases on the is-land of Cuba, giving special atten-tion to questions relating to the eti-ology and prevention of yellow fe-ver."

Preliminary Work of theBoard

The president of the Boardwas Major Walter Reed, an

Army surgeon from Virginia.Reed had recently distinguishedhimself working on prevention oftyphoid fever in Army campsand was a logical choice. An En-glishman, Dr. James Carroll,was primarily responsible for thebacteriology work of the Board.He had been associated withReed since 1893 and was highlytrusted by him. Dr. Carroll wouldsoon turn out to be the first ex-perimental case of yellow fever.

Dr. Aristides Agramonte, a Cu-ban physician, handled pathologyand autopsies. He was believed tobe immune to yellow fever due toprior infection. The fourth and finalmember ofthe Board was Dr. JesseW. Lazear. He had been a medicalschool classmate of Agramonte's at

Columbia University and was hiredby the Army as a contract surgeon.In exactly four months, Lazear, whohandled the mosquito colonies,would be dead from yellow fever atthe age of 34.

D Jesse W. Lazear

The goals of the Board wereclear: 1) determine the nature ofBacillus icteroides which a famousItalian bacteriologist claimed wasthe cause of yellow fever, 2) performbacteriological studies on patientsand victims, and 3) explore thetheory of insect transmission of yel-low fever.

The insect theory had been pro-moted in Cuba since 1881 by Dr.Carlos J. Finlay. Finlay claimed thatthe mosquito Culex fasciatus (nowknown as Aedes aegypti) transmit-ted yellow fever but he had beenunable to convince the scientificcommunity during 20 years of ex-periments. Dr. Finlay's experienceand assistance would prove invalu-able to the success of the Board.

The Board began work on June25t", 1900 and spent the rest of Juneand July on bacteriology. Cultureswere made from the blood and tis-sues of 11 yellow fever victims. Allresults for B. icteroides were nega-tive. The Board could not produce a

single shred of evidence to supporta bacterial etiology for yellow fever.

At about this time, Reed becamemore and more influenced by threepieces of information. First, a pris-oner in a guard house in Cuba diedfrom yellow fever on June 18t". Noneof the eight other prisoners in thecell got sick, including one who sleptin the dead man's bed! Second, justthree years before in 1897, SirRonald Ross had proved that mos-quitoes were the vectors of avianmalaria. Finally, Dr. Henry RoseCarter had recently worked out theextrinsic incubation period concept(the time from when a mosquitopicks up the virus to when it cantransmit it) for yellow fever. Carterwas a quarantine officer in Cubaand had a great influence on thework of the Board.

On August 1 ', 1900 the Boardand a few others met on the porchof the officers' quarters. They de-cided to test the mosquito theory. IImembers of the Board agreed thatthey must take the same risks whichnecessity would soon compel themto impose upon any volunteers.Shortly thereafter, fate played herhand.

John Kissinger

On the next day, August 2d,Reed was ordered to Washingtonto finish a critical report on typhoidfever. During his absence, Lazearand Carroll began to test the mos-quito theory. On August 30th, Carrollwas taken seriously ill with yellowfever transmitted by the bite of oneof Lazear's mosquitoes. On Sep-tember 4t" a second case was pro-duced and Reed was notified inWashington.

Under mysterious circum-stances, Lazear was bitten on Sep-tember 13, became ill with yellowfever on the 18", and died on the25t". There was considerable con-troversy surrounding his death. Af-ter realizing the gravity of his illness,Lazear claimed he was bitten by ac-cident while working in the hospital.Others, possibly including Reed, feltthat Lazear had experimented onhimself and, as his death couldhave been ruled a suicide, the storywas fabricated so that his familywould not be denied insurance ben-efits. Unfortunately, Lazear's labo-ratory notebook, which may answerthis question, was lost shortly afterthe experiments were concluded.

On October 3rd Reed returned toCuba and immediately readLazear's notebook. ALthough heunderstood that none ofthese threecases had been produced undercontrolled conditions, he still wrotethe now classic paper in which theBoard stated the following conclu-sions: 1 Bacillus icteroides standsin no causative relation to yellow fe-ver, butwhen present should be con-sidered a secondary invader in thisdisease, and 2) the mosquito servesas the intermediate host for theparasite of yellow fever.

Camp Lazear and theControlled Experiments

Now, the challenge was to con-clusively prove that mosquitoeswere the primary mode oftransmis-

$#aq eat*, Winter 1996 15

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sion. To do this, and to disprove thefomite theory, controlled experi-ments using human volunteerswere necessary. On November20t", 1900, Camp Lazear was es-tablished. It consisted of seven Armytents and would serve as a quaran-tine station for the volunteers.

Volunteers were drawn fromArmy soldiers and Spanish immi-grants. Each volunteer signed aninformed consent and was offered$100 in gold for volunteering andanother $100 if he got yellow feverduring the course of the experi-ments.

Army Private John R. Kissingerand a civilian clerk named JohnMoran were the first to volunteer theirservices to the Board, After MajorReed explained the inherent dan-gers and proposed payment, bothmen declined the money, making ittheir sole stipulation thatthey shouldreceive no monetary reward. Uponhearing this, Reed touched his capand said, "Gentlemen, salute you."

John Kissinger

Allow me to digress for a few mo-ments and tell you how JohnKissinger got to Cuba. He was bornon July 25, 1877 on afarm in HenryCounty, Ohio. His family moved toLiberty Mills, Indiana when he wasquite young. Being very patriotic, hejoined the local militia when he was19 years old, After the sinking of aU.S. ship in Havana harbor in 1898,Kissinger joined the Army to fight inCuba but the war ended before hegot that chance and he was dis-charged. Still determined to fight, here-enlisted, hoping to see action inthe Philippines but due to a foot de-formity, he was transferred to thehospital corps and sent to Cuba.

After being quarantined in CampLazear for over 30 days, Kissingerwas experimentally infected with yel-l6 Winter 1996, ,.f

Continued from page 16

low fever by mosquito bite, becameill on December 8", and sufferedthrough a moderate case of the dis-ease. Writing about Kissinger at alater date, Reed said, "In my opin-ion, this exhibition of moral couragehas never been surpassed in theannals of the Army of the UnitedStates." In just a few brief days, themosquito theory had beenchanged to fact.

The Fomite House

Although the Board hadclearly demonstrated thatmosquitoes could transmityellow fever, it had not ruledout the fomite theory. Re-member, this was the ac-cepted mode of transmis-sion of the day.

In order to address thisquestion, a small building(14 by 20 feet in size) wasconstructed. When the building wasready for occupation, three largeboxes filled with sheets, pillow-cases and blankets were placed in-side. This was no ordinary linen,however. Many of the articles hadbeen purposely soiled with a liberalquantity of black vomit, urine andfecal matter from recent victims ofyellow fever.

At 6 p.m., three American vol-unteers entered the building, gin-gerry unpacked the inen, thoroughlyshook all items, used the linen toprepare their beds and settled in fora good night's sleep. One volunteer,overcome by the stench during un-packing, raced outside and vomitedbut returned to complete the experi-ment.

This scenario was followed forthe next 20 days, although the menwere allowed to spend the daytimehours in a tent. On December 19th

they were placed in quarantine forfive days; all remained in perfecthealth.

For good measure, the processwas repeated from December 21 tto January 10", using different vol-unteers. This time, however, theyactually slept in patients' soiled pa-jamas.

And finally, just to be sure, it wasrepeated again from January 11 ,h tothe 31t. As an added treat, this timethe men covered their pillows with

The Fomite House

towels soaked with blood of yellowfever victims. Again, all remainedwell. At a later time, two of thesevolunteers were given yellow feverby blood injection which proved theywere not immune while in the fomitehouse.

In a letter written on December10th, Reed mentioned that the vol-unteers in the fomite housewere re-lieved to hear about Kissinger'scase. The fomite theory was nowhistory.

The Mosquito House

If fomites did not spread yellowfever, the logical question before theBoard was how does a house be-come infected with the disease? Toaddress this question, they built asecond house, similar in construc-tion to the first, was built. It consistedof two rooms separated only by a

screen partition. It was very sanitarycompared to the fomite house and

all articles entering the houseweresteamed.

On December 21 s, 1900, withReed watching from one side, 15female Aedes aegypti were re-leased on the other. These mosqui-toes had all fed on patients' bloodteeming with yellow fever virus andsubsequently held for the appropri-ate extrinsic incubation period; their

cargo was deadly.

At noon, our yellow fe-ver susceptible friend, JohnMoran, clad only in a nightshirt and fresh from a bath,entered the room and re-clined on a cot. For the next30 minutes he was bittenby seven mosquitoes whilehe held a hand lens andwrote a detailed account ofwhat he saw. Later that dayhe re-entered and took fivemore bites and the next day,three more bites.

Most importantly, during each ofMoran's visits, two volunteers thatwere also susceptible to yellow fe-ver, remained on the other side ofthe partition at all times and sleptthere each night from December21' to January 8. They remainedin good heath. For John Moran,however, Christmas Day came witha bang. He awoke to find himselffirmly in the grip of the case of yel-low fever he seemed so intent onhaving.

Aftermath

The conclusions of the Boardwere published on February lff",1901 and presented at the PanAmerican Congress in Havana thesame month. The first four conclu-sions dealt with mosquito transmis-sion and the extrinsic incubation pe-riod for yellow fever.

Conclusions 5 through 8 dis-cussed infection by blood injection,immunity, incubation period of the

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Continued from page 17

disease in humans, and the rejec-tion of the fomite theory. Number 9stated how a house became in-fected with yellow fever. Conclusion10 was important as it proposedthat the spread of yellow fever couldbe stopped using mosquito control

UNDAYmeasures and patient isolation tech-niqDes. Finally, the Board statedthat although the mode of transmis-sion was now known, the specificcause of yelJow fever remained amystery.

The Board produced 22 casesofyellow fever under controlled con-ditions; 14 by mosquito bite, six byblood injection and two by injectionof filtered serum. It is significant tonote that, although yellow fever mayhave a case fatality rate of 50% orhigher, the controlled experimentsproduced no deaths. It has beensaid that the Board had good nurs-ing, good diet and good patient han-dling but most of all it had good luck.Any fatalities among the volunteersmay have terminated the experi-ments immediately.

The Board Members

The events in Cuba left WalterReed physically and mentally ex-

hausted. The ordeal of human ex-perimentation had exacted a size-able toll. In Washington, he wasplagued by the daily routine of mili-tary life and his work on yellow fe-ver was attacked by jealous friendsand enemies. Finally, and most in-credibly, he was charged with be-ing absent without leave in connec-tion with presenting the Board's find-ings in Indianapolis. Reed, who wasthankful his life had not been lived invain, understood none of this andwas humiliated.

in November, he confided tofriends that he was a very sick man.On November 17" he was operatedon for a ruptured appendix. Fivedays later he developed peritonitis,became unconscious and died onNovember 23r, 1902 at the age of51 and at the zenith of his career.

Major Reed is interred in Arling-ton National Cemetery where a

granite headstone and bronzeplaque commemorate his accom-plishments. Among other items, theplaque states, "He gave to man con-trol over that dreadful scourge, yel-low fever."

Dr. James Carroll, Reed'strusted assistant, died in 1907 fromheart disease which he blamed onhis case of yellow fever. He left be-hind a wife and five children. Dr.Agramonte became a professor atthe University of Havana and, as faras know, lived a long and produc-tive life. He never received any ma-terial reward for his share of thework on yellow fever.

As mentioned earlier, Dr. Lazeardied from yellow fever at the age of34, leaving behind a wife and two

young children, one ofwhom he hadnever seen. He is interred in Balti-more, Maryland where a battery inthe harbor is named for him. Thewidows of Reed, Carroll and Lazearall received pensions of $125 permonth from the government.

Benefits of the Work

The benefits derived from thework in Cuba are truly inestimable.Without doubt, thousands of liveswere spared and millions of dollarswere saved. Dr. William Gorgaswas a sanitary engineer for the

Dr. William Gorgas

Army in Cuba. Skillfully applying therecommendations of the Board, hecoordinated an intensive mosquitocontrol campaign, Within a fewshort months, yellow fever was lit-erally eliminated from Havana.

General Gorgas then applied hismethods in Panama where yellowfever had been a major obstacle tothe completion of the Panama Ca-nal. Within a short time, yellow fe-ver was gone and the Canal a real-ity.

The United States continued tohave outbreaks of yellow fever after1900 but the fear and panic associ-ated with prior epidemics was nowreplaced by determination and co-operation in the fight against mos-quitoes.

Continued on page 22

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Continued from page 18

The Volunteers

asked to return all the money. For-tunately, after a short time the pen-sion was restored.

And what ever happened to thebrave volunteers without whomnone of this would have been pos-sible? Most were lost track of. Afterabout ten years, however, it wasdecided that a Congressional Medalof Honor should be given to each ofthem. Curiously, medals wereawarded only to those who got sickor who slept in the fomite house.There was no medal just for volun-teering. On occasion, reunionswere held which were generally wellattended.

John Kissinger's fate after Cubais an interesting tale. He survived hisbattle with yellow fever but not with-out some telling losses. He left theArmy in 1901 and returned to Indi-ana to try his hand at farming but hewas not physically strong enough forthis labor. He then went to Seattle,Washington where he worked atvarious jobs, got married and oper-ated a restaurant.

After returning to Indiana,Kissinger, while walking home onenight, collapsed and lost the use ofhis legs for 12 years or so. An appli-cation to the government for pen-sion, which Kissinger did reluctantly,was turned down as John could notprove his disability was caused byhis bout with yellow fever.

To make ends meet, Mrs.Kissinger took in washing with Johnslowly and awkwardly assistingwhile propped in a chair. She alsoscrubbed post office floors. Finallyin 1907, Congress reconsideredand Kissinger was awarded a pen-sion of $12 per month and a few fa-vors such as free street car rides.Outraged at this action, manypeople wrote letters on Kissinger'sbehalf. As a result of this public out-cry, Kissinger was given a pensionof $100 per month in 1911. Incred-ibly, the pension was later with-drawn and the Kissingers were

In the early 1920's, theKissingers moved to a small townin Indiana called Huntington, whichjust happens to be my home town.So now you know how got inter-ested in this story. Eventually, theAmerican Medical Association be-came aware of the Kissinger's plightand through it a fund was raised topurchase a house for them to livein.

Kissinger finally started to re-ceive some of the accolades he sorichly deserved. He was a modestman and rarely spoke about theevents in Cuba unless asked. Hewas interviewed often by the mediaand despite all the attention, re-mained a humble soul. Even Holly-wood got into the act; John and hiswife Ida were the guests of honorfor the 1938 premiere of the movieYellow Jack, the story of the eventsin Cuba.

The Kissingers lived in Hunting-ton until they thought it best to enterthe Indiana Soldiers' Home inLafayette. Hoping to relieve the painin his joints, Kissinger moved toFlorida where he died on July 16",1946 at the age of 68. His remainswere returned to Huntington wherehe and his wife are buried. Hisgravestone reads, "A martyr to yel-low fever in the interest of humanityand a hero of the Spanish-Ameri-can War."

On the hospital grounds in Hun-tington is a plaque dedicated toKissinger. As the plaque states,Kissinger, Moran and the other vol-unteers were, and still are, quiet he-roes. Also in Huntington, one cor-ner of the courthousemuseum isdedicated to Kissinger. The displaycontains several of Kissinger's uni-forms, documents pertaining to theyellow fever experiments, numer-ous awards and photographs.

Continued on page 26

Continued from page 22

A painting by Dean Cornwellshows all the central figures in thefight against yellow fever in Cuba.Although this exact scene probablydidn't take place, it is a fitting tributeto those involved. The two figureson the right clad in blue medic jack-ets are our two heroic young men,John Kissinger and John Moran.

In closing, would like to para-phrase Dr. Howard Kelly from hisbook on Walter Reed: the inspira-tion of these men lies in the fact that,though men of war, they ravaged nodistant lands, destroyed no tens ofthousands to make their reputation,but, by quiet methods when therewas no strife, saved countless livesand swept away a hideous plaguewhich from time immemorial hadperiodically visited our shores, dev-astated our fair land, and too oftensnatched from the years of peaceand plenty all their blessings.

Acknowledgments

thank CAPT Ben Mitchell andAmyanne Cope for reviewing themanuscript. The late Dr. A. R. Barrprovided encouragement and en-thusiasm during the genesis of thisproject.

26 Winter 1996,