Yellow Fever Investigations 163

Chapter Nine

Yellow Fever Investigations

Reports appeared in the medical literature and lay press of two phenomenal discoveries achieved independently—and nearly simultaneously— -in Brazil and Mexico. In 1885, Dr. Domingos Freire, a chemist working in 

the medical school in Rio de Janeiro, Brazil, and Dr. Manuel Carmona y Valle in 

Mexico announced that they had found the agent of yellow fever and developed 

protective vaccines. These revelations caused a great stir among physicians in the 

United States, particularly along the Gulf coast. While the medical profession was 

divided on the veracity of these discoveries, the editor and staff of the New Orleans 

Medical and Surgical Journal lambasted Freire’s abilities and experience as a 

pathologist and microscopist, declaring he had failed to describe or demonstrate 

the microbe. The following month the journal pronounced Carmona y Valle as 

“opposed to sound logic and accurate observation,” and it also doubted his statistical acumen.1

 These discoveries were a major topic of discussion at the November 

American Public Health Association (APHA) meeting in Washington, DC. 

Dr. Joseph Holt, president of the Louisiana State Board of Health, introduced 

resolutions requesting that a government-sponsored investigative commission 

validate these new claims. Congress debated until January 1887, and then approved 

one government-employed physician to conduct the investigations.2

Although Sternberg’s selection as the sole investigator was probably a foregone 

conclusion, Holt organized intense lobbying efforts to ensure his old friend would 

be named when wrangling over amendments to the bill ended. He wrote to Secretary of State Thomas F. Bayard endorsing Sternberg’s candidacy in late February. 

In early March, Representatives Robert T. Davis (MA) and Newton C. Blanchard 

(LA), Senator James B. Eustis (LA), and Judge John H. Reagan (TX) presented the 

same endorsement directly to President Grover Cleveland, and Surgeon General 

John Moore added his recommendation for Sternberg by mid-April. Two weeks 

later, Sternberg had presidential orders in hand, his luggage packed, and a complete field outfit for bacteriological investigations prepared.3
164 The Life and Science of Surgeon General George Miller Sternberg 

Given the nature of the visit, the Sternbergs were presented at the Court of Princess Isabella, Regent of the Empire, during the absence of her father, Dom Pedro 

II, soon after their arrival. This point of protocol was meticulously planned, yet 

it appears that coordination for Sternberg’s visit with Freire was somewhat faulty. 

Freire was in France demonstrating his inoculation technique and would not return 

until the first of July. The director of the medical school provided Sternberg with 

working space in Freire’s laboratory and introduced him to two of Freire’s assistants, Doctors Chapot Prevost and Joachim Caminhos. They received him warmly 

and provided a tour of the laboratory, but Sternberg was not impressed with the 

facility. Freire’s microscope objectives were not state-of-the-art, and there were no 

culturing apparatus, dyes, solid culture media, or histological preparations. Liquid 

cultures were stored in three large cabinets marked “yellow fever,” “cholera,” and 

“cancer.” Sternberg also learned that the yellow fever vaccine and inoculations 

performed in the city had divided the medical profession of Rio de Janeiro into two 

camps. Supporters consisted mainly of younger physicians and Freire’s students, 

who considered the criticisms—hurled at a man they considered to be the “Pasteur 

of Brazil,”—to be based purely on jealousy. The opposition was composed of older 

physicians and leading members of the Imperial Academy of Medicine—all skeptical of their colleague’s results and claims—and some had challenged his methods 

and use of statistics. The populace of the city was not impressed with Freire’s public 

inoculation program either. When insufficient numbers of volunteers failed to 

come to his Vaccine Institute, Freire obtained government approval to vaccinate 

in private homes. His vaccinators invaded poor tenements by stating they were 

members of the board of health and claimed police authority to vaccinate by force, 

if necessary. The public outcry over this abuse was tremendous and supported by 

Freire’s detractors. With this firestorm engulfing his inoculation program, it is odd 

that Freire chose to be absent when Sternberg arrived.4

Until Freire returned, Sternberg cultured the contents of flasks that supposedly contained the Cryptococcus, reviewed inoculation results from the preceding 

three years, and collected epidemiologic data from those inoculated. With the 

yellow fever season ending, he sought out cases and collected blood and black 

vomit for culture. Sternberg was given use of a culture oven in Dr. Joao Baptista 

de Lacerda’s laboratory at the Museum of Natural History. While various bacilli 

grew in the Esmarch tubes he used, Sternberg could find no organism in the 

cultures provided or in the blood and vomit samples that fit the description of 

Cryptococcus xanthogenicus.

5

Freire returned on July 1. When he met with Sternberg three days later, he produced 

a culture tube of—what he described as—pure Cryptococcus growing on agar-agar 

that he had brought back from France. Freire described in detail the growth and 

pathologic characteristics of the organism and how it proliferated in all organs and 

fluids, and he demonstrated his method of examining body fluids. To ferret out 

the organism in tissues, Freire pulverized the tissue in a mortar with sterile water—a 

process known as trituration—and then filtered the extract through a linen cloth. 

A drop of extract was then put on a slide with a cover slip, and observed. One can 
Yellow Fever Investigations 165

imagine Sternberg’s impressions as he watched Freire perform these primitive and 

obsolete laboratory techniques, but he tried to remain diplomatic. Freire was 

completely unfamiliar with solid media cultures and thin-section organ preparation, and when questioned about the use of aniline dyes, Freire indignantly 

replied he was studying the microbe in the fresh state and felt it was unnecessary 

to “mask them, disguise them under a costume of carnival, in order to please 

certain microscopists...”6

Sternberg determined the organism Freire presented him was Staphylococcus 

aureus—a skin contaminant—that did not fit any of the descriptions provided 

and produced neither spores nor pigment as Freire claimed. He concluded, “The 

only explanation of this wonderful versatility as to form and color...which I 

can conceive of is...that Dr. Freire has mistaken deformed blood corpuscles, 

fat globules from the liver, and the debris of tissue elements in his trituration...

for micro-organisms.”7 Sternberg knew he was now on “a wild goose chase,” but 

persevered with a thorough investigation. Blood taken from confirmed yellow 

fever cases in local hospitals was cultured, and tissue sections from fatal cases 

were examined. Of 34 inoculated culture tubes, 28 remained sterile. A variety 

of bacilli and micrococci grew in the remaining six tubes, a result attributed 

to accidental skin contamination when blood was drawn. Sternberg’s tissue examinations provided an excellent example of his compulsive, exacting nature in 

investigational research. He noted in his report, “In all infectious diseases...due 

to the presence of a parasitic micro-organism in the blood, this organism may 

be demonstrated in properly stained thin sections of tissues. In such sections we 

often obtain cross-sections of small blood-vessels in which the blood corpuscles 

are in situ, and in which a stained micro-organism...would be very apparent.”8

Sternberg found his Brazilian colleague’s animal inoculation experiments and 

vaccine production to be just as imprecise and illogical as the rest of his work. 

Freire had inoculated monkeys, dogs, pigeons, and guinea pigs with blood from 

yellow fever patients all to no avail, but found injections of black vomit or 

cultures made from it were lethal to small rodents. It was obvious to Sternberg 

that the animals had died from septicemia induced by one or more of the various 

organisms in this material. Freire also attempted to demonstrate the lethality of 

the pure cultures of C xanthogenicus that he brought from France. First, Freire 

explained, the virulence of the organism, which was lost during the long voyage, 

had to be regenerated by injecting one gram of Cryptococcus bouillon culture into 

a pigeon. Four hours later, the regeneration was complete, the bird was killed, 

and one gram of cardiac blood was injected into the abdominal cavity of a guinea 

pig. This guinea pig survived, yet two others inoculated with unregenerated cultures died within 10 days of injection. To Freire, who concluded they died from 

yellow fever, this experiment vindicated his theory. Sternberg just shook his head 

in disbelief. What proof was there that the virulence of the cryptococcus had been 

reconstituted in so short a time? What proof existed that the organism injected 

was truly in the cardiac blood withdrawn? Cultures of this blood remained sterile. 

Sternberg remarked later, “Both of these guinea-pigs were supposed to have died 
166 The Life and Science of Surgeon General George Miller Sternberg 

of yellow fever, although they had been inoculated with a culture not ‘regenerated’ 

by passing it through the blood of a pigeon, and one which he had taken with 

him to Paris and back. Yet he repeatedly asserts...the virulence of his microbe 

becomes quickly attenuated in cultures preserved for a short time.... Dr. Freire 

was unwilling to show me his method of inoculating man...and stated...the fact...

these guinea-pigs had died was evidence...this culture—which had crossed the 

ocean and back—was too virulent to be used as a vaccine. Yet his experiments had 

been inaugurated with a view to regenerating the virulence of this same culture, 

upon the assumption...it was too attenuated to kill guinea-pigs.”9 To produce his 

vaccine, Freire injected blood from a yellow fever victim into a guinea pig or rabbit. Blood taken from this animal was injected into a second of the same species, 

and serial passages were repeated through six or seven animals. Blood from the 

last of these was cultured and serially passed at least four times in liquid culture 

media. The last of these cultures was used to inoculate the population of Rio de 

Janeiro. Again, Sternberg concluded the only reason anything grew in the culture 

vessels was because the original inoculum had been contaminated somewhere in 

the process.10

There was no C xanthogenicus. No laboratory animals had died from yellow fever 

and no protective vaccine had been produced. But, to be fair to Freire, Sternberg sifted 

through three years worth of immunization data. As he stated, “...these inoculations have been made on so large a scale, and the statistical results...appear so 

favorable to his method...it becomes necessary to analyze these statistics; and if...

they establish the fact that the mortality from yellow fever is very much less among 

those who have been inoculated...than among non-inoculated persons exposed in 

the same way, we will be obliged to concede the value of his method, although the 

rationale of this protective influence may not be apparent.”11 Sternberg found Freire 

had little epidemiological or statistical finesse and a very poor understanding of 

yellow fever’s natural history. Freire assumed person-to-person transmission and 

that the risk of disease was the same from year to year and from month to month. 

He failed to consider differences in exposure risk due to age, duration of residence 

in Rio de Janeiro, or time of year. Observation and follow-up were also inaccurate. 

Persons who had died from other causes or departed Rio de Janeiro before the 

yellow fever season were counted, and certain segments of his population were 

counted twice. Sternberg concluded that “...there is no satisfactory evidence that 

Dr. Freire’s inoculations have had any prophylactic value.”12

The Sternbergs sailed from Rio de Janeiro on August 11.13 Mrs. Sternberg’s 

memories of the voyage are few, other than it was dull and uncomfortable. Her 

husband was completely engrossed in compiling his report, and she filled in her 

time by making a card catalog of his notes, but the boredom was tedious. “If we 

were going home how happy we would both be,” she said.14 Then, although she 

knew he had been directed to Mexico by the president, she asked, “Why do you 

want to go to Mexico?”15 Her husband looked up from his papers and gazed at her 

tenderly, “Because I have given so much of my time and strength to the investigation 

of the cause and spread of yellow fever, that I feel I have exhausted all the legitimate 
Yellow Fever Investigations 167

experimental methods that could elucidate the subject. I hope in Mexico I can 

arrange to make human inoculations. In our own country this is not possible, and 

I now think that is the only way this problem will ever be solved.”16 Sternberg had 

hoped to make such experiments—transmission from person to person via blood 

injections—while in Brazil, but the opportunity did not present itself.

By the time the ship arrived in Barbados, quarantine authorities had been notified 

of smallpox epidemics in Rio de Janeiro and Pará. No one was permitted to leave 

the ship. After the passengers and crew were examined for evidence of smallpox 

and provisions were taken on, the ship continued to St. Thomas where the same 

rigid quarantine was in effect. Passengers could depart the ship only to go to the 

quarantine station where they were charged $3 per day for board and $5 per day 

quarantine tax that went to the station physician. Sternberg had always deplored 

this method of sustaining quarantine operations as nothing less than extortion. 

Irritated by the current quarantine system and frustrated by being trapped on a 

vessel moving farther away from Mexico, he could only continue with his report 

and hope the October 1 deadline for his investigations would be extended.17

Upon arrival at the quarantine station just outside of New York Harbor, he was 

again exasperated by what passed for disinfection. A man, who accompanied the 

port’s deputy health officer, poured a liquid into a bucket full of some powder. He 

lowered it into the hold and allowed it to remain there for an hour. At the end of 

this time, the ship departed for the wharf. Sternberg was curious about what was 

in the bucket, so he asked the ship’s surgeon to go with him to inspect it. They 

opened the hatch and hauled up the bucket. Sternberg could not detect any odor of 

disinfectant emanating from the hold, yet when he stuck his nose into the bucket 

he perceived that the reaction of liquid and powder had produced chlorine gas. He 

was told this small amount of material had disinfected the entire hold. Sternberg 

commented later, “The only object...I can conceive of depends upon the fact...

there is a fee for disinfecting, which must be paid by the agents of the ship: at least 

I was so informed by one of the officers.”18 The Sternbergs arrived in Baltimore on 

September 4. He was granted an extension of 20 days for his report and departed 

immediately by rail for Mexico City.19 

In Mexico City, Sternberg proceeded to the National Medical College of Mexico, 

where he met Carmona y Valle, director of the faculty. Sternberg was delighted 

with the laboratory, which contained a complete set of Robert Koch’s culture 

apparatus, two large Zeiss microscopes with a full set of objectives, and a large 

English binocular microscope. It was also obvious Carmona y Valle knew how to 

use this equipment effectively. Carmona y Valle’s yellow fever theory was based 

on a fungal origin. Accordingly, zoospores produced by Peronospora lutea damaged renal tubules, blocked urine outflow, and formed yellow spores that gave the 

typical skin color to disease victims. Carmona y Valle confidently demonstrated 

them in capillaries of liver tissue sections and provided cultures from urine of 

yellow fever patients. While Sternberg found Carmona y Valle’s knowledge of scientific methods admirable, he also found glaring errors in its technical application. 

Sternberg demonstrated Carmona y Valle’s spores to be masses of red blood cells 
168 The Life and Science of Surgeon General George Miller Sternberg 

altered by preservation fluids. He determined that Carmona y Valle’s cultures contained various commensal organisms from the distal urethra caused by improper 

collection techniques and bore no etiological relationship to yellow fever.20

Carmona y Valle produced his vaccine by allowing urine from yellow fever 

patients to evaporate in shallow plates. The residue was mixed with distilled water, 

and the vaccine was ready for subcutaneous injection. He inoculated himself in 

1881. By November 1885, he had injected 1,358 persons in and around Mexico 

City. None of these people became ill with the disease, but apparently it never 

dawned on Carmona y Valle that his success was attributable to the fact that yellow 

fever did not exist in the Mexican capital, except for a few imported cases. In Vera 

Cruz, the story was different. In early May 1885, yellow fever struck the military 

garrison there, resulting in 17 cases and eight deaths. Carmona y Valle inoculated 

the remaining 380 soldiers and six prisoners, but of these 28 became ill and 19 

died. Sternberg pointed out that these statistics, although not supportive of Carmona 

y Valle’s method, were essentially useless. Sternberg concluded, “A simple perusal 

of Dr. Carmona’s published work is sufficient to convince any competent bacteriologist that, owing to a defective technique and inexperience in bacteriological 

researches, he has fallen into serious errors of observation and of inference, and...

his supposed discovery has no scientific basis.”21 

During his investigations in Vera Cruz, Sternberg met Dr. Daniel Ruiz, director 

of the city hospital. Ruiz vehemently denied the infectious nature of yellow fever 

and had no faith in Carmona y Valle’s inoculations. He—like Sternberg—believed 

if the yellow fever agent actually resided in the blood and urine, then injecting 

these substances from the sick to the susceptible should produce the disease. 

Unfettered by moral or legal research considerations in Mexico, Ruiz had attempted 

such an experiment in 1885 with negative results, but gladly repeated them for 

Sternberg. Unfortunately, only three volunteers could be found. Two of these 

volunteers were injected with blood from a patient who was found at autopsy to 

have died of leukemia and not yellow fever. The third was injected with 50 cubic 

centimeters of blood from a patient with a confirmed mild case of the disease; 

however, as he was in the eighth day of his illness, he was beyond the period where his 

blood could transmit the virus, a fact unknown to Ruiz and Sternberg at the time.22

Sternberg returned to Baltimore in late October. At the last meeting of the APHA 

in Toronto, he became president of the association. His presidential address, to 

be given shortly in Memphis, was long, but well crafted. In this bully pulpit, he 

wanted to establish several objectives critical to the public health of the nation and 

motivate the membership to pursue them vigorously. He lamented the demise of 

the National Board of Health, a sound idea whose implementation had been faulty. 

He advocated a centrally located bureau under its own cabinet officer, directed by 

a commissioner with enough administrative staff to ensure efficiency and a laboratory of bacteriologists, chemists, and sanitary engineers. The commissioner would 

have a technical advisory board consisting of the surgeon generals of the army, 

navy, and marine hospital service; and presidents of state boards of health, 

who would have no executive power nor receive pay. Sternberg then focused 
Yellow Fever Investigations 169

on quarantine and imported diseases. He applauded the vigilance of quarantine 

activities along the southern coasts, but cautioned them against complacency. 

No system was foolproof and, furthermore, none of the six international sanitary 

conferences agreed on quarantine regulations. The only way pestilential diseases 

could be contained within acceptable limits was through education, continual sanitary improvements, and efficient quarantine stations funded not by commerce but 

by the federal government and supported by the public with constant supervision by 

trained sanitary officers. Here is where the APHA could make an impact at the 

national and state levels in this area. Sternberg’s vision of the APHA mission was to 

identify effective sanitary measures, teach community and personal hygiene, and 

conduct special investigations, such as the value of protective inoculations and water 

supply purity in various American cities and towns. Moreover, he recommended 

that a special fund be created by the association to encourage such investigations.23

Construction on the Hoagland Laboratory had begun in the summer. With 

Sternberg’s return, plans proceeded in earnest for staffing and equipping it and 

developing a solid program of instruction. By mid-January 1888, however, he 

recognized that an assignment in New York City was unrealistic for the next two 

years at least. He reiterated his promise to provide not 10 but 12 weekly lectures, 

and on these days he also taught practical laboratory exercises for several hours. 

No army billets existed in New York for Sternberg, but clearly the prospect of continued government-funded yellow fever research and a functioning laboratory he 

could use as an operational base kept him at his Baltimore station. He was no 

closer to positively demonstrating the etiology of yellow fever than he had been 

nine years earlier. He had prepared hundreds of cultures, blood smears, and tissue 

sections; studied epidemiologic patterns; and modeled plausible etiologies until 

he was mentally exhausted. A sufficient amount of disease and cadaveric specimens—both of which were lacking in Brazil and Mexico—was required to conduct what he considered a thorough investigation, and, therefore, he would have 

to be in an endemic area during the epidemic season. Havana, Cuba, was the natural 

choice, and Sternberg began working to this end from the moment he returned 

from Mexico.24

By the time he wrote to Raymond in January, he had another strong motivation 

to go to Havana. Dr. Paul Gibier, a French bacteriologist, had gone to Havana in 

November 1887 to verify Freire’s work. After demonstrating to himself that Freire 

was in error, he conducted his own blood studies. Finding no microorganisms in 

the bloodstream, Gibier then looked in the alimentary canal. The intestinal contents of many cases yielded a certain bacillus—later named Bacillus lepina lethalis

by Sternberg—frequently enough to suggest he was on the right etiologic trail. 

Sternberg had closely watched Gibier’s studies. He stated later, in March 1889: 

“The possibility that the infectious agent in yellow fever may have its habitat in the 

alimentary canal, occurred to me several years ago, and I determined, in advance 

of my visit to Havana last spring, to give special attention, to a bacteriological study 

of the intestinal contents.”25 In 1875, Sternberg had clearly stated his belief that the 

yellow fever organism—considered by him at the time to be a fungus—infected 
170 The Life and Science of Surgeon General George Miller Sternberg 

individuals via the gastrointestinal membranes. He concluded in his Report Upon 

the Prevention of Yellow Fever by Inoculation that a thorough search of alimentary 

canal microorganisms was needed, but his investigations in 1879 and 1887 do not 

discuss it in detail, and his reports were not tremendously concerned with pathological findings in the stomach or intestines. The reason for this lies primarily in 

the fact that from 1879 onward he was looking for blood-borne bacteria whose 

major pathological impact was on the liver and kidneys. Although it is impossible 

to know all the things he considered in regard to his work during these extensive 

studies, he may have seen his primacy in the search for a yellow fever agent slipping away to a colleague who—thanks to Sternberg’s previous work—knew where 

not to look for the organism. He received the desired orders to Cuba in the third 

week of April.26

Whether Gibier enthusiastically received Sternberg when he stepped off the 

steamer is unknown, but he gave him cultures of his newly found bacillus. By 

mid-May, Sternberg was convinced Gibier’s organism, while lethal to laboratory 

animals, had nothing to do with human disease. He then scrutinized the gastrointestinal tracts of every yellow fever patient he could find, but obtaining enough 

autopsies was difficult. Between May 12 and June 6, he performed only 10 and 

had to return home because his funding ended. In his official report from 1890, 

he wrote, “My first five autopsies, made in 1888, gave a negative result. In case 6 

[May 23], autopsy 4 hours after death, colonies of two different kinds were obtained in cultures from the blood, liver, and kidney. One of these was my bacillus 

a. ... Again, in cases 7 and 8 the result was negative; but in case 9, in which the 

autopsy was made 5 hours after death, numerous colonies of bacillus a developed 

in my cultures from blood, liver, and kidney.”27 This version of events written more 

than a year later and after many experiments and much contemplation does not 

coincide with what Sternberg reported in his letters home. Interestingly enough, 

he began to see positive results in his search for a gastrointestinal agent of yellow 

fever almost immediately. On May 17, he wrote home in an exuberant mood: “I 

have some good news for you. I believe that at last I have discovered the yellow 

fever germ in the stomach and intestines. I have also obtained it in cultures from 

the kidney and urine. I will not attempt to give you particulars but there are several 

good reasons for believing that the bacillus which I get in my cultures is the long 

sought yellow fever germ...I have only had two autopsies as yet, but they were 

typical cases and both give me the bacillus in question.... It is not found in the 

blood. As I am the first one to cultivate it and to describe its characters I must be 

considered the real discoverer.... I am feeling very well and very cheerful at what I 

believe to be a successful search.”28 Four days later, he wrote home again in the same 

ebullient mood: “I am getting on famously and...believe I have at last discovered 

the yellow fever germ. I have now had three autopsies and find it in every case, not 

in the blood but in the stomach and intestines. It kills rabbits and guinea pigs and 

in a guinea pig which died on the 4th day the characteristic black liquid was in 

the intestines in large quantity... I am feeling very well and very happy at having 

accomplished that which I so long have been trying for.”29 By May 23, Sternberg 
Yellow Fever Investigations 171

had performed six autopsies and found Bacillus a in all stomachs and intestines. 

He told his wife: “The announcement I made to you is fully confirmed and I shall 

publish the discovery very soon. Dr. Gibier who has been here four or five months 

has published the discovery of a different germ and he is wrong. I have not encountered his bacillus in any of my cases....”30 His optimism over Bacillus a faded 

by the end of the first week in June as cultures failed to grow. In a letter home on 

his 50th birthday, he stated, “I can see now that I will not be able to make a definite 

announcement of a discovery. The best I can say is that there is some probability 

that my Bacillus A is the yellow fever germ. I shall have a lot of work to do again 

after my return home.”31 Some probability went to zero in July after he conducted 

an extended series of comparative experiments at Johns Hopkins. Sternberg demonstrated that Bacillus a was identical to the Bacillus coli commune of Escherich, 

a resident of healthy intestines worldwide and what is known as Escherichia coli.

32

In his final report, one sees the steady, methodical, precise researcher. Sternberg 

had had time to conduct further trials, compared the results, pinpointed errors, 

and evaluated the whole objectively in his Baltimore laboratory. In fact, he experimented with Gibier’s Bacillus well into December 1888. Standing in stark, uncharacteristic contrast to this is his rapid rejection of Gibier’s work and the equally rapid 

acceptance of his own. Based on material derived from only three autopsies and 

the deaths of a few laboratory animals, Sternberg consigned Gibier’s Bacillus to the 

trash heap of scientific history and replaced it with Bacillus a. Only 10 autopsies 

were performed during his eight weeks in Havana and, although he did not find 

Gibier’s Bacillus in any of them and found Bacillus a in only three, this confidence 

in such little data defies the proper scientific conservatism that Sternberg always 

touted as prudent in research. Moreover, he was prepared to publish the results 

derived from this meager information immediately. His almost adolescent 

gloating over his colleague’s error and his own discovery is also uncharacteristic. 

It may well represent—just as in his argument with Dr. Mallet in 1881—not only a 

self-styled priority of ownership in regard to yellow fever studies, but also a sense 

that, by virtue of his lengthy research on the subject, the right of discovery was 

reserved for George Sternberg.

In searching for the cause of yellow fever Sternberg, Gibier, Burgess, and their 

Cuban colleagues—Carlos Finlay, Claudio Delgado, Fernandes Malo, and others—

discussed treatment modalities at length. Contemporary active therapy, including 

emetics, purgatives, quinine, and calomel (mercuric chloride), was considered 

unsatisfactory at best by physicians who saw a lot of the disease. These physicians 

tended more and more to advocate expectant or symptomatic treatment. Sternberg 

approached treatment from a more physiological perspective. His remedy consisted of 150 grains of sodium bicarbonate and 0.3 grains of bichloride of mercury 

mixed in a quart of ice-cold water and given in a dose of one and three-quarter 

ounces every hour. Sternberg described the logic of this therapy: “My principal 

object...was to test a decidedly alkaline treatment from the outset of the attack, 

with a view to relieving the gastric distress and acid vomiting which is a prominent 

feature of cases treated by the expectant method, and...to render the highly acid 
172 The Life and Science of Surgeon General George Miller Sternberg 

urine neutral or slightly alkaline, in the hope that secretion would be more abundant and the tendency to suppression diminished.”33 Also, he hoped this would 

prevent “those structural changes which give rise to passive hemorrhage from 

the stomach and suppression of urine—two symptoms which present themselves 

in a majority of the fatal cases.”34 He stated further: “Bichloride of mercury in a 

comparatively small amount was added...not with the idea that it would to any extent destroy the pathogenic microorganisms in the intestine, but as an antiseptic, 

which might be useful in preventing fermentative changes in the stomach, which 

would perhaps be favored by the free administration of an alkali. The idea has also 

occurred to me that the specific germ may possibly find a suitable nidus in the 

acid secretions of the stomach, and in this case the administration of an antiseptic 

in combination with an alkali would be the most rational treatment. Still, I have 

not given much weight to this idea.”35 After Sternberg departed Havana in June, 

12 cases—all confirmed as yellow fever by Dr. Burgess—were treated successfully 

using Sternberg’s therapy at the Garcini Hospital. Eight other cases treated in the 

same hospital by other methods were considered controls and of these five died. 

Sternberg was pleased, but realized the number of cases treated was too small to 

substantiate the value of his method and wanted a thorough trial.36

While Sternberg continued to search for the etiology of yellow fever in cultures 

and tissue preparations during the summer in Baltimore, he also lit a fire under 

Joseph Raymond to find a laboratory assistant for him at the Hoagland Laboratory. Courses were to begin in October and desperation was beginning to set in. 

Although Sternberg told him that anyone—even a student with a short course in 

bacteriology in Welch’s laboratory—would be acceptable, none of the candidates 

had satisfactory credentials. This state of affairs continued until mid-July when 

he found a talented prospect, George T. Kemp, Ph.D., at Johns Hopkins. Kemp 

had studied with H. Newell Martin and William Henry Welch, and the more 

Sternberg talked with him, the more enthusiastic he became that Kemp was the 

best candidate. In a letter to Hoagland in July, Sternberg described Kemp: “He 

is about 27 or 28 and has been a student in different departments of the University for about eight years. I think he is a man who would help us to build up 

the reputation of the Hoagland Laboratory for original scientific work, and who 

might take my place if in a year or two if I find it necessary to resign the honorable position to which you have appointed me...I think you will find him a very 

well qualified and useful man.”37 Kemp interviewed successfully with Hoagland 

and Raymond later in the month and was appointed as associate director of bacteriology and physiology.38

The summer of 1888 marked the 10th anniversary of the devastating yellow 

fever epidemic in the Mississippi Valley. In those 10 years, the United States had 

been virtually free of the scourge. A large share of the credit for this situation was 

given to the southern public health establishment, which had matured during 

the 1880s through the sound leadership of men such as Joseph Holt of Louisiana, 

Wirt Johnson of Mississippi, and Jerome Cochran of Alabama. By 1888, all of 

the southern states except Florida had state boards of health. It was, therefore, 
Yellow Fever Investigations 173

doubly unfortunate for Florida that the next large yellow fever epidemic would 

originate in Jacksonville.39

Sternberg acted on the research opportunity presented by the Jacksonville 

epidemic. On September 5, he received approval from the War Department to 

proceed to Florida. Before he could execute these orders, he became aware—either 

from the newspapers or directly from Cochran—that the Jacksonville outbreak 

had spread to Decatur, Alabama. Sternberg stated he went to Decatur rather than 

Jacksonville because of the higher mortality in the former city and because he 

knew he would get excellent support from his old friend Cochran. He arrived in 

Decatur on the evening of October 3 and “found that yellow fever of a most malignant type was prevailing, and...the mortality had been very great.”40 The town 

would suffer 154 cases and 35 deaths, which was a mortality rate of 23 percent, 

by the first of November. Of the 10 physicians in Decatur, nine became ill and 

five died. The four remaining doctors, B. F. Cross, E. J. Conyngton, W. C. Buckley, 

and E. M. Littlejohn, fought the disease using Sternberg’s new therapy, and Littlejohn assisted him as well in a makeshift laboratory. Sternberg performed his first 

autopsy later that night on a 35-year-old man who had died only an hour earlier. 

Although during the next month he only obtained permission for two more autopsies—none of which provided any positive information—his main purpose in 

Decatur was to answer a question that Gibier had raised in Havana. Assuming 

Gibier’s Bacillus, Bacillus a, or some other bacillus caused the disease, but was 

found only sporadically in post-mortem tissue specimens, was it also reasonable 

to assume that the bacillus was present in the intestines early in the disease and then, 

after performing its mischief, disappeared before death? To answer this question, 

Sternberg collected and cultured a total of 35 fecal specimens, but found nothing.41

The epidemic in Florida and Alabama also provided an excellent opportunity 

to evaluate Sternberg’s treatment on a large scale, and physicians used it in both 

states with excellent results. In Decatur, 64 cases were treated from the beginning 

of their illness with a 6 percent mortality. The control group of 90 individuals not 

treated by this method suffered a mortality of 34 percent. From Jacksonville, a 

mortality of only 4.7 percent was credited to Sternberg’s therapy, and many physicians agreed that the method was remarkable in preventing urine suppression. 

Sternberg proudly reported these glowing statistics in the medical literature, but 

failed to describe his methods convincingly. It was assumed that if the patient 

was treated and survived, he or she did so because of the treatment. Randomized 

double-blind, controlled therapeutic trials were unknown at the time and, while 

confounding was not discussed as such, Sternberg understood the concept. 

He realized that race, age, and gender affected infection and recovery rates, as 

did severity of infection, but ignored other factors, such as nursing care, previous 

health of the patient, and severity of infection, which he knew were important in 

recovery. He had not allowed Freire or Carmona y Valle to use shoddy epidemiologic 

techniques, but Sternberg’s desire to make an impact—if only therapeutically—

on yellow fever seems to have clouded his analytical judgment. Furthermore, 

Sternberg apparently assumed the free flow of urine equated to successful 
174 The Life and Science of Surgeon General George Miller Sternberg 

alkalinization with bicarbonate, but no test for urine acidity was done to verify 

this assumption. He had constructed a rickety therapeutic bridge part way over 

a wide clinical chasm and then made a leap to the other side based on faith in 

his statistical results. Over time the ratio of recoveries to deaths using Sternberg’s 

therapy declined dramatically, and his treatment went away.42

A frost followed by a hard freeze ended the Decatur outbreak. Sternberg arrived 

home in early November. Two weeks later, he delivered his first lecture to 200 

physicians and students gathered in the lecture hall at the Hoagland Laboratory. 

The lecture, which was reported in the Brooklyn Daily Eagle, reviewed bacteriologic science from the time Robert Koch established his research methods and 

techniques. Sternberg said the Germans led the way and made the most progress 

because of the support and encouragement provided by an enlightened government. He was saddened because the United States had contributed so little to 

bacteriology, but closed by stating, “Let us hope that we are entering upon a new 

era. Here in Brooklyn private munificence has provided the means of research 

which the government should have provided long ago. The fault will rest with 

the medical profession if active workers are not found to avail themselves of the 

facilities provided.”43

December was a crowded month for Sternberg. At Johns Hopkins, experiments 

with cultures from Havana and Decatur continued and preparations of tissue sections 

were made and photographed. He refined his lectures and prepared remarks for 

the official dedicatory ceremonies at the Hoagland Laboratory. Opening ceremonies 

for the laboratory commenced at 8:00 pm on December 15 with introductory remarks by Doctors Charles H. Hall, Hoagland, Sternberg, and the Honorable Joshua Van Cott, Sr. Sternberg commented that, with such a finely appointed laboratory, he saw no reason why the Americans could not achieve the glorious deeds 

of the French and Germans, and received warm applause. The guest speaker for 

the evening, Dr. H. Newell Martin, presented a history of laboratory development 

from the era of the Ptolemies in Egypt to the current German models. He said that 

previous scientific research had been government funded and controlled. Martin 

proudly noted—much to Sternberg’s chagrin—that American laboratories were 

not so encumbered and, therefore, worked not for the government, but for the 

good of mankind!44

Experiments conducted through December left Sternberg with no definite yellow 

fever organism. He lobbied once again to go to Cuba during the entire epidemic 

season, and orders dated February 5, 1889 directed him to return to Havana. In 

the last half of February in Brooklyn, he made new photomicrographs of all the 

organisms he had encountered during his laborious investigations of the past 

two years and gathered the bacteriologic equipment necessary for four and a half 

months of study. Hoagland and Raymond—still intent on securing Sternberg as 

a full-time professor of bacteriology—unsuccessfully attempted to lure him with 

financial and professional inducements. Sternberg’s declination has never been 

explained. Probably for all of his irritation with the army concerning its disregard 

for his routine research, Sternberg was dedicated to the Medical Department, and 
Yellow Fever Investigations 175

furthermore, it was his link to government funding for continued yellow fever 

research. Hoagland offered a fine salary, shares of collegiate profits, and research 

facilities in Brooklyn, but he could never support yellow fever research projects on 

the scale to which Sternberg had become accustomed. He arrived in Havana on 

March 16. Through the cooperation of the local Spanish government, Sternberg 

was given free access to both military and civilian hospitals. The auxiliary yellow 

fever commission had become a permanent research organization, and it provided 

continuity for continued Cuban-American research efforts.45

Of all the men on the auxiliary commission, Carlos Finlay was the most tenacious, scientifically courageous, and prescient in yellow fever research. His yellow 

fever studies predated the First Havana Yellow Fever Commission, but after studying 

Sternberg’s 1879 photomicrographs, he formulated a novel hypothesis of yellow 

fever transmission based on the fact that “red blood globules are discharged unbroken in the hemorrhages of yellow fever. This fact taken in connection with 

the circumstance that those hemorrhages are often unattended with any perceptible break in the blood vessels, while...they constitute a most essential clinical 

symptom of the disease, led me to infer that the principal lesion of yellow fever 

should be sought for in the vascular endothelium. The disease is transmissible, it 

attacks but once the same person, and always presents in its phenomena a regular 

order comparable with that observed in the eruptive fevers...yellow fever should 

be considered as a sort of eruptive fever in which the seat of the eruption is the 

vascular endothelium.”46 It occurred to Finlay that, for transmission, infectious 

material from within a blood vessel of a yellow fever patient had to be withdrawn 

and transferred into the interior of a blood vessel of a nonimmune individual. 

Since person-to-person transmission did not occur, this had to be accomplished 

by some intermediate agent capable of tapping into blood vessels silently and 

repeatedly, an ability “the mosquito satisfies most admirably through its bite.”47 For 

the next two years, Finlay studied the habits of Culex cubensis. He noted only the 

female took numerous blood meals very soon after mating or else she died, and 

he theorized the blood was required for the development of fertilized eggs.48 He 

postulated there must be a “transportable substance, which may be an amorphous 

virus, a vegetable or animal germ, a bacterium, etc., but...constitutes something 

tangible which requires it to be conveyed from the sick to the healthy before the 

disease can be propagated.”49 Finlay was convinced the mosquito conveyed this 

substance, but attempts to prove his theory during the summer of 1881 by infecting mosquitoes and inoculating five nonimmunes failed.50

Retrospectively, Finlay was a visionary. However, he was not the first to indict 

the mosquito of complicity in disease transmission. Sir Patrick Manson had 

reported certain developmental stages of Filaria bancrofti occurred in Culex 

mosquitoes in 1878.51 Manson believed, however, that filaria were not transmitted 

by the mosquito’s bite, but, upon the mosquito’s death, escaped into the surrounding 

water. Individuals were infected when they consumed this water. At the time of 

Finlay’s presentation, direct disease transmission from vector to human was too 

large of a leap of faith for many of his contemporaries. The devil was in the details 
176 The Life and Science of Surgeon General George Miller Sternberg 

of his hypothesis and experimentation. Finlay, like Sternberg, was searching for 

an etiologic agent that fit the bacteriologic construct of the era. He assumed the 

mosquito transmitted the disease agent via a contaminated proboscis, the natural 

hypodermic needle it uses to obtain a blood meal, found a contaminating organism, 

and assumed it came from the blood of yellow fever patients. 

Sternberg studied cultures sent by Finlay in the winter of 1887–1888. He had 

seen this organism occasionally in stomach and intestinal contents of yellow fever 

patients and noted it was also a common skin contaminant of patients in Havana, 

Vera Cruz, and Rio de Janeiro. Finlay also assumed the mosquito was competent 

to transmit the infection immediately after charging itself with infected blood. 

The yellow fever virus requires a 9–12 day incubation in the mosquito host before 

the infection can be transmitted. Finlay applied his mosquitoes to his volunteers 

within two to six days after biting a yellow fever victim. He continued these inoculations over the next eight years, but obviously they could never provide sufficient 

statistical significance to prove his theory. He continuously, but unsuccessfully, 

tried to enlist Sternberg’s support for the idea of mosquito transmission. Sternberg 

did not consider “the subject as demanding serious attention for the reason that 

the mosquito does not inject the blood drawn from a yellow fever patient into the 

inoculated individual, but it enters the insect’s stomach, and whatever remains after 

its meal has been digested is passed per anum. When the mosquito introduces its 

proboscis into the individual who is to be inoculated it is for the purpose of withdrawing blood, and it is difficult to see how any inoculation can occur, unless some 

virus has adhered to the exterior of the delicate instrument during the considerable interval which elapses after one full meal before the insect can be induced to 

fill itself again.”52 He found this possibility highly improbable. Furthermore, Ruiz’ 

attempts in Vera Cruz to transmit yellow fever by blood injections had been negative. 

Although Sternberg did not consider these experiments conclusive, neither did he 

have any experimental evidence to show the disease agent was truly in the blood 

of yellow fever victims. Although Finlay and Sternberg appear to have maintained 

an amiable personal and professional relationship, Sternberg’s a priori rejection of 

mosquito transmission, which meant essentially the subject was ignored in American medical circles, rankled Finlay.53

Upon Sternberg’s arrival, the yellow fever season was just beginning, and initially cases were few and sporadic. Therefore, he studied the bacterial flora of Havana’s 

sewers, not because he expected to find anything definitive, but because, as he said, 

“it [was] good preliminary work.”54 He corresponded frequently with Franklin 

Mall, who was studying anaerobic organisms in the Johns Hopkins Laboratory.55

In the second week of April, Sternberg read a letter by Dr. Frank Billings, director 

of the pathological laboratory at Nebraska State University, in the Medical Register 

of Philadelphia, which got his full attention. Billings had been studying pathological sections of tissues taken from six yellow fever patients that had been sent to 

him by Daniel Burgess in Havana; material from two cases had come from autopsies numbers 9 and 10, performed by Sternberg in 1888. The Nebraska physician 

claimed that he had found the organism described by Babes in 1885 “in the blood 
Yellow Fever Investigations 177

in every section and in great numbers, every authority to the contrary” and confidently declared “against all contradiction, that in such a disease as yellow fever, 

where one finds one organism closely and sharply in many sections and all parts 

of these sections,...that that organism is the cause of the disease of which the 

individual died.”56 Billings had to be aware of the authority he was challenging and 

that authority quickly sent a letter to Mall: “Now if this is true it is a matter of great 

importance that I should know it,” Sternberg wrote, “and if it is false the sooner I 

am satisfied of the fact the better for my peace of mind. You have all of my material 

in your hands, & Dr. Billings has given his method. Will you not take the matter up 

at once & give it your best attention & report to me as soon as possible. If Dr. Billings 

can demonstrate microorganisms by the methods he has given you ought to be 

able to do so by the same methods. Please show this letter to Prof Welch & say to 

him that I earnestly hope him to give a little time to this matter, & either to make 

mounts by the methods described or to examine yours & let me know his opinion. 

Certainly the matter is sufficiently important to claim some of his time. I want to 

know the truth about it as soon as possible for if you find what Billings claims to 

find it will have a bearing upon my further experimental work.”57 By mid-May 

Mall’s analysis, presumably with the assistance of Welch and possibly William T. 

Councilman, had allayed Sternberg’s apprehensions enough for him to let the 

issue rest for the summer. Later Sternberg demonstrated the organism Billings had 

identified as Babes bacillus was identical to his Bacillus a (E coli).58

The expected epidemic of yellowjack failed to materialize early. Sternberg complained to Martha that he was “not getting on at all” with his research because he 

had no autopsy material.59 But he added, “it can’t be long before some of the unfortunate Spanish soldiers will fall victims to yellow fever.”60 The first fatal case among 

the soldiery did not occur until April 23. He obtained permission for an autopsy 

of this patient and another five days later. From then until late August, Sternberg 

conducted a total of 30 autopsies and another 18 on persons dead from maladies 

other than yellow fever for comparison. He studied fresh and preserved specimens 

of kidney, liver, stomach, and intestines; prepared aerobic and anaerobic cultures 

of blood, urine, stomach, and intestinal fluids; identified and photographed a large 

number of organisms from these cultures; and injected them into laboratory animals to determine their virulence. His spirits rose and fell as his work proceeded. 

On May 6, he told Martha the discovery of the yellow fever organism would not 

be easy, but was sure that “whether I demonstrate the germ or not my work will 

stand as scientific work of value in this department of research.”61 A week later 

he lamented to her, “so far as I can see, I am no nearer a solution of the main 

question,” and added, “I am doing my work thoroughly and, if I don’t demonstrate 

the specific germ, it won’t be for want of working faithfully by the most approved 

methods, and no one else is likely to make an easy discovery in the field if I have 

to give up in the end.”62 

About this time Sternberg found what he designated as Bacillus X. This organism 

resembled Bacillus a structurally, its virulence in laboratory animals far surpassed 

anything he expected, and it was “the most promising yet.”63 If found in a majority 
178 The Life and Science of Surgeon General George Miller Sternberg 

of autopsies “it may turn out to be the specific microbe I have so long been in 

search of.”64 Experiments over the next 10 weeks continued to bolster his faith in 

the primacy of Bacillus X. “I am feeling more encouraged with reference to my 

Bacillus X,” he wrote home at the end of July, “and I think now I will probably be 

able to announce it as a probable specific agent, even if I can’t claim to have made 

a complete demonstration of it.”65 Twelve days later he determined the source of 

the organism’s rapid lethality. “I am again quite hopeful with reference to my Bacillus X,” he told his wife, “and have proved by experiment that it produces a deadly 

volatile ptomaine. I have collected this in distilled water from culture of Bacillus 

X and injected it into rabbits, which die from such injections in a few hours.”66 His 

optimism was understandably high, but tempered perhaps by memories of his 

impetuous rush to claim the prize from Gibier in 1887, for he added, “You can say 

to my friends who ask you that I have strong hopes...I have discovered the right 

germ but am not yet prepared to announce positively that this is the case.”67

Sternberg sailed for home on August 31. For the next seven months, he pursued 

experiments with Bacillus X in the comfort of the Johns Hopkins Laboratory, had 

Councilman verify old and new slide preparations, and reviewed all his yellow fever 

research over the past three years. His Report on the Etiology and Prevention of 

Yellow Fever, submitted June 21, 1890, was a complete and all-encompassing tour 

de force that defined and described all that was known about the disease both 

from the clinical and research perspectives. Regrettably, Sternberg was unable to 

rule in or out Bacillus X as the specific etiologic agent. After years of difficult, 

painstaking effort, travel, and separation from Martha, he effectively concluded 

his work with two sentences: “The specific infectious agent of yellow fever has not 

been demonstrated. The most approved bacteriological methods fail to demonstrate 

the constant presence of any particular microorganism in the blood and tissues of 

yellow fever cadavers.”68 Sternberg was sorely disappointed and commented that, 

“No one can regret more than I do that the...etiology of yellow fever is not yet 

solved...but I at least have not to reproach myself with want of diligence or failure to embrace every opportunity for pursuing the research. The difficulties have 

proved to be much greater than I anticipated at the outset.”69

Although Sternberg did not discover the long-sought yellow fever organism, he 

took some comfort in at least having been “able to exclude in a definite manner a 

majority of the microorganisms which I have encountered in my culture experiments, as well as those which various other investigators (Freire, Carmona, Finlay, 

Gibier) have supposed to be the specific cause of the disease.”70 In a world where 

fame is gained by making great discoveries and where there are no laurels for second 

place, Sternberg’s yellow fever investigations, like his work with the pneumococcus, have become only a footnote in the annals of medical history. However, his 

summation above was accurate. Using state-of-the art methods and equipment, 

meticulous technique, and reasoning, he eliminated all microorganisms found by 

these methods as candidates for the etiology of yellow fever. It was no small feat 

in 1890 and virtually brought significant yellow fever research to a close until the 

last half of the decade.