CHAPTER I. Yellow Fever and the Discoveries of Its Transmission

YELLOW FEVER AND THE DISCOVERIES OF ITS TRANSMISSION

Yellow fever for two hundred years before the Spanish-American War caused great loss of life and much destruction of wealth. Every few years portions of the United States would become infected with this disease. In the earlier part of this period the disease was more or less local. As the Mississippi valley became more thickly populated, the extent of the disease and the injury caused became very much augmented. The epidemic of 1878 was probably the deadliest and most extensive epidemic of yellow fever which ever affected the United States. In this epidemic over thirteen thousand people in the Mississippi valley alone lost their lives, and the loss of wealth is estimated at considerably more than one hundred millions of dollars.

It is very difficult to convey to a reader any idea of the conditions which exist during an epidemic of yellow fever. All business is entirely paralyzed, the quarantines not allowing any communication between the affected districts and those not affected. In an epidemic of any extent this means hundreds of local quarantines. Some idea of the condition of affairs can be obtained by picturing what would occur in any community if all the income of that community should entirely cease for six months. And this was the condition of business all over the Mississippi valley every time yellow fever gained entrance.

The population originally feared yellow fever on account of the poverty, suffering and business depression always caused by the quarantines which had to be enforced to prevent its spread, and in time people came to associate this idea of dread with yellow fever itself. When this disease was announced in a town, everybody left who could. The sick were frequently left without care, and often a great deal of cruelty and cowardice was shown. If a person escaped from an infected region and became sick with the disease, or sick from any other cause, he was generally treated as if he were a leper, and would often be left to starve or die on the roadside.

It requires continuously warm weather for the yellow-fever mosquito to breed in sufficient numbers to propagate yellow fever; therefore, this disease never became endemic in the United States. I mean by endemic, existing all the year round and over a number of years. The frosts of winter, wherever they occur, either destroy all the yellow-fever mosquitoes, or reduce their number below the point at which yellow fever could be propagated.

It was known in the United States that yellow fever was always brought somewhere from the littoral of either the Gulf of Mexico, or the Caribbean Sea, and the city of Havana, located on the northern coast of the island of Cuba, was known to be the center of this endemic area.

Yellow fever in 1898 was looked upon as the example of a filth disease, par excellence, and it was thought that if Havana were put in a proper state of cleanliness, it might cease to be the great point of infection for the United States. It was known that yellow fever had existed in the city of Havana continuously for one hundred and fifty years. It is interesting to note that the endemic infection of Havana occurred in 1762, when Havana was besieged and captured by American troops. I say American troops, because the expedition was largely composed of men from the present United States, then colonies of Great Britain. It is also interesting to note that this infection was supposed to have been brought by a vessel from Vera Cruz.

Yellow fever peculiarly affects shipping, and time and again ships in the harbor of Havana have had every living soul of their crew die from this disease, and these vessels would have to lie there for months until another crew could be obtained.

When we went to Havana in 1898 we knew no more of the sanitation of yellow fever than we had known a century before. The army which went to Santiago suffered as severely from yellow fever and other tropical diseases as any military expedition into the tropics had suffered before that time, and its death rate, had it remained, would have been just as high as was that of the French army of similar size, which was exterminated in the island of Haiti just one hundred years before.

A very deep impression was made upon me by the condition of our army at the end of two months’ campaigning in this tropical region. It was utterly used up and of no value whatever as a fighting machine. Fully four-fifths of the men were having fever. This small army of sixteen thousand men was as fine a body of soldiers when they landed at Siboney as could probably be gotten together, but after two months’ campaigning in this tropical jungle, and after several weeks of fever from which no one was free, their stamina and morale were completely gone. After the surrender of the Spanish garrison there was a complete let-down on our side. Everybody wanted to go home. No one could see any need of staying in Cuba, and every individual was perfectly certain that he would die if he remained there a month longer. Officers and men became nervous and hysterical. I commanded the base hospital at Siboney, and it was my disagreeable duty to select from day to day those who would have to remain. Many times every day the poor fellows, officers and men, would break down and cry when told that they could not leave on the next ship. I could form some idea of what it must have been among the French at Haiti when they knew that they could not get away, but had to stay and die.

Being immune to yellow fever, I made application to go with the troops that took possession of Havana. We arrived there in December, 1898. The military authorities concluded that this was the opportunity which the United States had been awaiting for the past two hundred years. Thinking that yellow fever was a filth disease, they believed that if we could get Havana clean enough, we could free it from yellow fever. It was felt that if we could eliminate Havana as a focus of infection, the United States would cease to be subject to epidemics. This meant so much to the United States, financially and otherwise, that the authorities determined to make all other efforts secondary to this sanitary effort.

The city was cleaned as well as it was possible to cleanse it. This remark applies as well to the private premises as to the public highways. Energetic and capable Army officers were placed at the head of various municipal departments, and these departments were thoroughly organized and made as efficient as possible. By the middle of the year 1900 all the city governments were perfectly organized, and were accomplishing all that it was possible for them to accomplish. I believe that Havana was cleaner than any other city had ever been up to that time.

The health regulations of the Sanitary Department, such as the isolation and care of yellow-fever patients, were thoroughly and carefully carried out. But in spite of all this work and care, yellow fever had been steadily growing worse ever since we had taken possession of the city, and in 1900 there were a greater number of cases than there had been for several years. The Cubans twitted us with the fact that all our cleaning up and expenditure not only had not bettered things, but had even made them worse. They called attention to the fact that the very cleanest and best kept portions of the city were by far the worst sufferers from yellow fever, and the evidence was so staringly before our eyes that we had to acknowledge the truth of what they said.

The health authorities were at their wits’ end. We evidently could not get rid of Havana as a focus of infection by any method we then knew.

A few years before this period, an Italian savant had announced in Brazil that he had discovered the organism which caused yellow fever. This organism was known as the bacillus icteroides of Sanarelli, and it was quite generally accepted that Sanarelli had proved this to be the causative agent in yellow fever.

Drs. Reed and Carroll had proved that the bacillus icteroides of Sanarelli was identical with the hog-cholera bacillus. They made this demonstration while comparing the bacillus X of Sternberg with the bacillus icteroides of Sanarelli. The work was carried on by them during the years 1897 and 1898, at the laboratory of the Army Medical Museum in Washington. The investigation was undertaken at the request of General Sternberg.

In 1899 our Public Health Service published the report of a board of medical officers who had been sent to Havana to investigate Sanarelli’s organism. This report made a great impression. Surgeon-General Wyman, in his letter transmitting the report says:

The findings of this Commission, verifying the discovery made by Sanarelli, and making still further advances than did Sanarelli himself by determining the specificity of the bacillus icteroides, and that the primary infection of yellow fever is received through the respiratory tract, in other words, verifying one discovery and making others of almost equal importance, at the same time eliminating incorrect theories, must be considered a notable achievement in medical science and one of the greatest practical value to the people of the United States and other countries infected, or liable to be infected by yellow fever.

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In view of the widespread interest which the report will excite and the practical deductions to be drawn therefrom, I have respectfully to request authority to have the same printed.

The findings of this Commission were:

First. That the microörganism discovered by Professor Giuseppi Sanarelli, of the University of Bologna, Italy, and by him named “bacillus icteroides” is the cause of yellow fever.

Second. That yellow fever is naturally infectious to certain animals, the degree varying with the species; that in some of the rodents local infection is very quickly followed by blood infection, and that, while in dogs and rabbits there is no evidence of this subsequent invasion of the blood, monkeys react to the infection the same as man.

Third. That infection takes place by way of the respiratory tract, the primary colonization in this tract giving rise to the earlier manifestations of the disease.

Fourth. That in many cases, probably a majority, the primary infection, or colonization, in the lungs is followed by a “secondary infection,” or a secondary colonization in the blood of the patient. This secondary infection may be complicated by the coinstantaneous passage of other organisms into the blood, or this complication may arise during the last hours of life.

Fifth. There is no evidence to support the theory advanced by Professor Sanarelli that this disease is primarily a septicemia, inasmuch as cases do occur in which the bacillus icteroides cannot be found in the blood, or organs in which it might be deposited therefrom.

Sixth. That there exists no casual relationship between the bacillus X of Sternberg and this highly infectious disease; and that this bacillus X is frequently found in the intestinal contents of normal animals and of man, as well as in the urine and the bronchial secretion.

Seventh. That, so far as your Commission is aware, the bacillus icteroides has never been found in any body other than of one infected with yellow fever; and that whatever may be the cultural similarities between this and other microörganisms, it is characterized by a specificity which is distinctive.

Eighth. That the bacillus icteroides is very susceptible to the influences injurious to bacterial life, and that its ready control by the processes of disinfection, chemical and mechanical, is assured.

Ninth. That the bacillus icteroides produces in vitro as well as in vita a train of the most marked potency; and that, from our present knowledge, there exists a reasonable possibility of the ultimate production of an antiserum more potent than that of Professor Sanarelli.

About the same time an officer of the Public Health Service, Dr. H. R. Carter, was making in Mississippi his epoch-marking observations upon the extrinsic incubation of yellow fever. Measured by the results produced, this was one of the most important papers ever written. Yet as high an authority as the Surgeon-General of the Public Health Service expected the greatest results to flow from the conclusions reached by this Board, and did not notice the report from his subordinate concerning the extrinsic incubation of yellow fever. The conclusions of his Board turned out to be all wrong and useless as to results. The report of Carter turned out to be pure gold, and was one of the great steps in establishing the true method of the transmission of yellow fever. I do not say this in criticism. It is almost impossible for contemporaries to judge the true value of discoveries, or to give the proper position to the men of their own time who make these discoveries.

General George M. Sternberg, the then Surgeon-General of the Army, was one of the leading bacteriologists of the profession, and was also one of the best known authorities on yellow fever. He doubted the findings of this Board, and obtained authority from the Secretary of War to appoint a board of Army medical officers to investigate this same subject. He appointed on this now famous and immortal board Reed, Lazear, Carroll and Agramonte. They came to Havana, and spent several months in investigating Sanarelli’s organism. They proved beyond peradventure that it had no causative relation to yellow fever, and identified it as a well-recognized organism.

It is an interesting historical fact that one of the yellow-fever patients in whom the Board of Public Health Service found Sanarelli’s organism was a patient of mine. He was a soldier, Private Patrick Smith, Eighth Infantry, a non-immune living in an infected part of Havana, so that I thought that he ought to be reported as a suspect. The case continued nine days, long enough to convince me clinically that the disease was not yellow fever. The symptoms in a case of yellow fever dying on the ninth day are always so well marked that the diagnosis should not be in doubt. But the Board found Sanarelli’s organism, and being themselves convinced that this was the organism of yellow fever, they believed the case to be that disease. It shows the necessity in scientific matters of being on one’s guard, and of approaching investigation with an open mind.

The Army Board having satisfied themselves that Sanarelli’s organism bore no relation to yellow fever, but was simply the ordinary hog-cholera bacillus, turned their attention to other matters, though they were always working in relation to yellow fever. They spent a great deal of time in examining the intestinal flora in cases of recognized yellow fever, but could find nothing that seemed to have any relation to this disease in a causative sense.

Being at that time the health officer of the city of Havana, and in that capacity having charge of all cases of yellow fever which occurred in the city. I necessarily came in contact with this Board a great deal, and with its various members. I was naturally much interested in the work, and kept in very close touch with it. The Sanitary Department of Havana had a commission of medical men to whom all cases of yellow fever were referred for diagnosis. I was a member of this Commission, and Dr. Carlos Finlay, Dr. Antonio Albertini and Dr. John Guiteras were the other members. Each of us had had a very large practical experience with yellow fever. It is likely, therefore, that our Commission was as accurate in its diagnosis of this disease as it was possible for fallible doctors to be. Most of Dr. Reed’s experimental cases were seen and passed upon by this Commission. Dr. Reed requested us to do so, in order that the diagnosis of his cases might be upon the same footing as the diagnosis of the other cases occurring in the city of Havana.

Dr. Carlos Finlay, of Havana, the physician just mentioned as being a member of our Commission, had ever since the year 1881 been investigating, thinking of and writing about the relation of the mosquito to yellow fever. He had convinced himself that this insect was the means whereby the disease was conveyed from person to person. Others before Dr. Finlay’s time had referred to the possibility of this being the case, notably Dr. J. C. Nott, of Mobile, Alabama. In March, 1848, he published in the New Orleans Medical Journal an article in which he maintained that the spread of yellow fever could not be explained by the assumption of a diffusible miasm in the atmosphere. But Dr. Finlay had given more attention to this subject than anyone who had gone before him. He had written upon it constantly from the year 1881. His argument from the then known facts with regard to yellow fever, showing from these facts that it was probably the mosquito that conveyed this disease, was most beautiful and logical. But a still more beautiful piece of reasoning was the induction that it was the stegomyia mosquito, out of the six or seven hundred species of mosquitoes, that conveyed yellow fever.

Dr. Finlay, in the twenty years before we went to Havana, had done a great deal of experimenting on the human subject with regard to yellow fever. But he had not been successful in transmitting the disease. He had no means of knowing that it took the mosquito twelve days from the time when she swallowed the blood of a yellow-fever patient to become herself infectious. Not knowing this fact, it was perfectly natural for Dr. Finlay to use his mosquitoes upon his experimental cases within the first four or five days after they had bitten a yellow-fever patient. At any rate, in a large number of experimental bitings of the human subject he did not have a single case in which the evidence was conclusive that yellow fever had been conveyed by the mosquito. Reed says of Finlay: “To Dr. Carlos Finlay, of Havana, must be given, however, full credit for the theory of the propagation of yellow fever by means of the mosquito, which he proposed in a paper read before the Royal Academy in that city at its session on the 14th day of August, 1881.”

The Reed Board, after many months of inconclusive work in other directions, turned their attention to Dr. Finlay’s mosquito theory. Dr. Reed discussed the matter with Dr. Finlay a good deal before he commenced his mosquito work, and was thoroughly familiar with Dr. Finlay’s arguments and ideas on the subject. Indeed, we all knew Dr. Finlay well, but were rather inclined to make light of his ideas, and none more so than I. He and I met every day on the yellow-fever Commission above referred to, and it is probable that every day for more than a year we had more or less discussion on this subject.

Dr. Finlay is a most lovable man in character and personality, and no one could be constantly thrown with him as I was daily for several years without becoming warmly attached to him and forming the highest estimate of his scientific honesty and straightforwardness. Being very familiar with yellow fever, both historically and clinically, I was constantly bringing to his notice instances in the past which could not be accounted for on the mosquito theory. He, with the greatest ingenuity, was equally ready to explain how the mosquito theory could be turned so as to meet just this condition.

Dr. Finlay is still living in retirement and comfortable old age in the city of Havana. When the American forces were withdrawn from Cuba in 1902, Dr. Finlay succeeded me as health officer under the Cuban Government. He has since been retired on a pension by that Government. I called on him in Havana several years ago, and found him enjoying his more than eighty years of age, and the honors that were being heaped upon him. He is one of the few great men who has had his work recognized during his lifetime.

Dr. Reed got from Dr. Finlay the eggs from which he raised the mosquitoes used in his experimental work. Dr. Finlay says on page 1 of his “Agreement between the History of Yellow Fever and Its Transmission by the Culex Mosquito”: “The experiments made by Drs. Reed, Carroll, Agramonte and Lazear were started in June, 1900, with a brood hatched from eggs of the identical insect which at Dr. Lazear’s request I had handed to him. All the successful experiments have hitherto been made with that particular mosquito.”

Dr. Reed says in his paper, “The Etiology of Yellow Fever, Preliminary Note”: “We here desire to express our sincere thanks to Dr. Finlay who accorded us a most courteous interview and has gladly placed at our disposal his several publications relating to yellow fever, during the past nineteen years; and also for ova of the species of mosquito with which he had made his several inoculations. An important observation to be here recorded is that according to Finlay’s statement, thirty days prior to our visit, these ova had been deposited by a female just at the edge of the water in a small basin, whose contents had been allowed to slightly evaporate; so that these ova were at the time of our visit, entirely above contact with the water. Notwithstanding this long interval after deposition, they were promptly converted into the larval stage, after a short period, by raising the level of the water in the basin. With the mosquitoes thus obtained we had been able to conduct our experiments. Specimens of this mosquito forwarded to Mr. L. O. Howard, Entomologist, Department of Agriculture, Washington, D. C., were kindly identified as culex fasciatus—Fabr.”