CHAPTER II. The Experiments of the Reed Board

THE EXPERIMENTS OF THE REED BOARD

After consultation, the Reed Board determined to experiment to see whether the mosquito really did convey yellow fever. But it was necessary to have a good deal of money and sufficient authority before starting in. The Board had come to Cuba for entirely different investigations, and had not been supplied with sufficient funds for these experiments. Fortunately for the cause of science and of humanity, we had as Governor-General of Cuba at that time General Leonard Wood, of the United States Army. General Wood had been educated as a physician, and had a very proper idea of the great advantages which would accrue to the world if we could establish the fact that yellow fever was conveyed by the mosquito, and his medical training made him a very competent judge as to the steps necessary to establish such fact.

General Wood during the whole course of the investigations took the greatest interest in the experiments, and assisted the Board in every way he could. Dr. Reed outlined to General Wood the course he expected to pursue, and General Wood was so convinced by Dr. Reed’s argument that he authorized the expenditure from Cuban funds of a sufficient sum and gave Dr. Reed ample powers as to the method of expenditure.

The Board then went to work in earnest along lines which seemed calculated to develop the facts in the matter. They started a laboratory at Camp Columbia, the American military station a short distance out of Havana. Here they bred their mosquitoes from eggs procured from Dr. Finlay, and here the first three experimental cases occurred. The first case was severe; the second case was that of Dr. Carroll, a member of the Board, and was well marked, and Dr. Lazear, another member of the Board, died of the disease. Dr. Lazear visited Las Animas Hospital and was bitten by the mosquito on September 13, 1900; was taken sick September 18th and died September 25th. Previously on August 16th, he had been experimentally bitten by a mosquito which had ten days before bitten a yellow-fever patient in the fifth day of the disease. We know now that ten days is too short a time for incubation in the mosquito, and the fifth day a period too late for the yellow-fever patient to be infectious.

Dr. Carroll was intentionally bitten. Dr. Lazear told me after he was taken sick, and a day or two before he died, that he recalled being bitten by a stegomyia three or four days before he was taken sick, and while he was at work at Las Animas, our yellow-fever hospital in Havana. He said that he had noticed the mosquito enough to recognize that it was a stegomyia, and had allowed it to fill and fly away without disturbing it. These three cases satisfied the Board that the stegomyia mosquito was the means of conveying yellow fever, but they determined that they would make such a demonstration of the matter that there could be no doubt in the mind of any reasonable person as to what had been proved.

With this idea in view they selected a spot a mile or more from the military camp, which was well isolated and had no habitations near it. They agreed that if they established an experimental station here and kept their patients in such a way that there was no possibility of their getting out and contracting the disease elsewhere, then the results obtained in this station would be due to measures taken there. They already had their stegomyia mosquitoes which they had reared from the eggs procured from Dr. Finlay. These mosquitoes they took to the hospitals in Havana, and allowed them to bite people sick with yellow fever. In the course of time the Board found that the mosquito to become infected with this disease must bite the sick human being within the first three days of his disease. This was a singular and unexpected phenomenon, and is explained in this way. The mosquito injects the yellow-fever parasite into the blood of the human being; these parasites at once commence ejecting toxins into the blood in which they are circulating; these toxins irritate the human cells with which the poisoned blood comes in contact and they begin to throw into the blood circulation antitoxins. By the end of the third day these antitoxins have become so concentrated in the blood that they always kill the yellow-fever parasite, and after the third day no yellow-fever parasites remain in the human body.

Yellow fever is a very fatal disease, and on the average kills the patient on the sixth or seventh day. Why then does death occur in yellow fever if on the average the patient lives to the sixth or seventh day, and yet always by the end of the third day the yellow-fever parasites have been routed and destroyed in the great battle which has taken place between them and the body cells?

Dr. Reed established this fact by finding that mosquitoes which had bitten a patient more than three days after the patient had developed yellow fever, did not convey the disease to the non-immune when he attempted to infect these non-immunes with such mosquitoes. On the other hand, he found that he was almost always able to give these non-immunes yellow fever when he used mosquitoes which had bitten the man sick with yellow fever within the first three days of his symptoms.

We have followed Dr. Reed now up to the point of his having infected mosquitoes and being ready to transmit the disease to non-immune human beings. A human being, in order that he may be liable to yellow fever, must be non-immune, and by immune I mean a person who either has had yellow fever, or has lived ten or more years in a locality where yellow fever prevails. An attack of yellow fever gives a great immunity to the disease, probably just as much as occurs in the case of smallpox. In practice, it is counted as absolute. In over two thousand cases of yellow fever which I have treated personally or seen in consultation, I have never seen a single case with a second attack, in which I saw the same individual in the first attack. I have seen several, however, who believed that they had had a previous attack, and I myself believe that I saw them in their second attack. I have by no means seen a quarter as many cases of smallpox as I have of yellow fever, yet I have seen more cases of second attacks of smallpox than I have of yellow fever. I feel confident, therefore, in stating that yellow fever gives fully as great immunity as does smallpox.

It is well known that in a yellow-fever endemic center such as was Havana during the nineteenth century native Havanese are not liable to yellow fever. They look upon their immunity as being absolute, and in my experience of fourteen years of life in such endemic centers I am inclined to accept their belief. The immunity of the native is explained by saying that he has probably had yellow fever in childhood when the disease was very mild, and that, at the time, it was overlooked and not recognized. This is the best explanation that, so far as I know, can be made of the facts in the case.

Certain it is that one of these endemic centers from which yellow fever has been banished for a number of years may have yellow fever as badly as a city in which it has never been endemic. Eighty years ago a native of Mobile, Alabama, or Pensacola, Florida, looked upon himself as being as immune to yellow fever as did the Havanese twenty years ago. But at the present time the native of either of these cities is just as liable to yellow fever as is the man from New York. This is explained by the fact that eighty years ago they had yellow fever so frequently in Mobile and Pensacola that all the natives had this disease in childhood. Within the last fifty years they have had it so infrequently that very few now living in those cities have had this disease.

Another phase of the same condition is seen in Ecuador. Guayaquil, the port of Ecuador, is located on Guayas River at sea level, not more than three degrees from the equator. Here yellow fever always prevails, and the native of Guayaquil is not liable to the disease and never has it. Quito, the capital of Ecuador, is situated about two hundred miles away, right on the equator, and on the great Andean plateau ten thousand feet above sea level. The stegomyia cannot breed at Quito, so that yellow fever has never occurred there. The native of Quito, therefore, has no immunity to yellow fever, and of this he is well aware. Guayaquil is the only seaport of Ecuador, and everyone leaving the country has to leave through this port. Hundreds of the natives of Quito have died of yellow fever contracted by passing through Guayaquil. The man from Quito dreads Guayaquil a great deal more than did the American in the early days fear Panama.

Dr. Reed, therefore, to make his experiments of any value, had to get human beings who had neither suffered from yellow fever itself, nor had lived long enough in an endemic center to acquire immunity. Havana for a number of years had received a considerable Spanish immigration. At the time to which I refer, it amounted to about twenty thousand a year. These immigrants believed that they were going to have yellow fever, and though they knew that a considerable number of them must succumb during the process, they were anxious to have the disease and be done with it. There was a very general belief among the Spaniards in Havana that a person with what they called “thin blood” as contra-distinguished from a robust, plethoric, full-blooded person, was much more likely to recover from yellow fever. They tried, therefore, with their newly arrived friends, relatives and dependents from Spain to bring about this condition of their blood. They kept them confined in a darkened room and fed them on a very limited diet, and certainly succeeded in rapidly reducing the strong, florid, robust Gallego to a very marked condition of anemia and debility. The Spaniard believed that he thus saved many lives. I was convinced that he thus killed a good many of his friends and dependents.

The newly arrived Spaniard, as soon as he had had yellow fever and could present a certificate of immunity, could command double the wages that he could get before he had the disease. So that when Dr. Reed proposed to some of these men that they should go out to his camp, have a mild case of yellow fever, be well cared for and when recovered be given by him a certificate of immunity, he found no difficulty in getting volunteers, and when, in addition to that, he promised each man who had the disease a bonus of two hundred and fifty dollars, the service became exceedingly popular.

Dr. Reed had prepared, as I have above mentioned, a very comfortable camp at an isolated point near Camp Columbia, well separated from all other dwellings. This camp was kept under military guard, so that no one could come and go without Dr. Reed’s knowledge. Here he placed his non-immune volunteer Spaniards whom he had gotten from Havana, and kept them under observation for two weeks, taking their temperatures every day so as to be sure that they had not contracted yellow fever before they went out to the camp.

At this point he made another important discovery in the mode of yellow-fever propagation. He found that the mosquito herself had to wait from ten to fifteen days after she had bitten a man sick with yellow fever before she herself conveyed the disease. He found that the mosquito for the first week or ten days after she had bitten the yellow-fever patient was entirely harmless though she fed freely on non-immunes. But after the twelfth or fourteenth day she would give the disease to every non-immune whom she bit. I have often seen the non-immune doctors and nurses at Las Animas Hospital put their hands in the jars where infected mosquitoes were kept during the first seven days of their infection and allow them to draw their fill of blood, for the purpose of feeding them, but they would not think of doing this after the seventh or eighth day. Two of these nurses afterwards contracted yellow fever from allowing mosquitoes to bite them after the twelfth day, and one of them, Miss Mass, died from the disease so contracted.

Dr. Carlos Finlay, in his many experiments on the human being, was unaware of these two facts with regard to the transmission of yellow fever: first, that the mosquito could only become infected by biting a human being within the first three days of his disease; and second, that she could only become infectious, that is, transmit the disease, when some twelve or fourteen days had passed since she had bitten the sick man. Dr. Finlay put a great many of his mosquitoes to the sick man after the third day, and in no case did he apply his mosquito to the non-immune twelve or fourteen days after she had bitten the infected person.

Dr. Henry R. Carter had published a paper on certain observations of his made during the epidemic of 1898 in the neighborhood of Jackson, Mississippi. It had long been known to men practically familiar with yellow fever that, in general, when you took a patient suffering from yellow fever into a house where yellow fever had not before existed, the people in that house did not at once develop the fever. We explained this by stating that it was due to the fact that the germs of yellow fever went from the patient to favorable grounds for development about the house, and there underwent some development which enabled them to produce the disease in non-immune man. We thought that the dirtier and more unhygienic were the conditions of the house, the more favorable were the conditions for the further development of the germs. Dr. Carter recorded a number of cases where the houses were isolated and the conditions favorable for making the observations, and found that the average time from the introduction of a yellow-fever patient into a house until the first case of yellow fever was contracted in that house, was about seventeen days. These observations were published to the world.

Dr. Reed was greatly impressed by this publication of Dr. Carter’s. He reasoned that if it were the mosquito which transmitted the disease, this period of extrinsic incubation must be due to a period of incubation in the mosquito. He says:

We were also much impressed by the valuable observations made at Orwood and Taylor, Mississippi, during the year 1898 by Surgeon Henry R. Carter, U. S. Marine Hospital Service, “A Note on the Interval between Infecting and Secondary Cases of Yellow Fever, etc.” (Reprint from New Orleans Medical Journal, May, 1900.) We do not believe that sufficient importance has been accorded these painstaking and valuable data. We observe that the members of the yellow-fever commission of the Liverpool School of Tropical Medicine, Doctors Surham and Meyers, to whom we had the pleasure of submitting Carter’s observations, have been equally impressed by their importance. (British Medical Journal, Sept. 8, 1900, pp. 656-70.)

The circumstances under which Carter worked were favorable for recording with considerable accuracy the interval between the time of arrival of infecting cases in isolated farmhouses and the occurrence of secondary cases in these houses. According to Carter, “the period from the first (infecting) case to the first group of cases infected at these houses, is generally from two to three weeks.”

The house having now become infected, susceptible individuals thereafter visiting the houses for a few hours, fall sick with the disease in the usual period of incubation, one to seven days.

Other observations made by us since our arrival confirmed Carter’s conclusions, thus pointing, as it seemed to us, to the presence of an intermediate host, such as the mosquito, which having taken the parasite into the stomach, soon after the entrance of the patient into the non-infected house, was able, after a certain interval, to reconvey the infecting agent to other individuals, thereby converting a non-infected house into an “infected” house. This interval would appear to be from nine to sixteen days (allowing for the period of incubation) which agrees fairly closely with the time required for the passage of the malarial parasite from the stomach of the mosquito to its salivary glands.

In view of the foregoing observations we concluded to test the theory of Finlay on human beings.

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Dr. Reed had, however, been working for some time before he came to these conclusions. His first nine cases bitten between August 11 and August 25, were all unsuccessful. The next two, bitten on August 27 and 31, were positive and were well-marked cases of yellow fever.

But Dr. Reed’s work was now brought to a stand-still. He found that all his Spaniards were deserting, and that he could get no more for love or money to come to the camp. The work from being much sought had become very unpopular. For some time he was unable to find any good reason for this. The story told in Havana was that the American soldiers, who were doing the guard duty for the camp, had found an old lime kiln in the lower part of the grounds. In this kiln they had placed a lot of bleached old bones, and here they would take the newly arrived Spaniard and darkly insinuate that these were the bones of their predecessors in Dr. Reed’s camp, and that if they did not leave before they were bitten by Dr. Reed’s mosquitoes, their bones would soon be bleaching in the same place. It was useless for Dr. Reed to argue and explain. This ocular evidence was too strong for any argument by word of mouth, and Dr. Reed had to give it up.

Our soldiers had seen that the disease was very mild; that the patients while they were in camp had the very best of high living and a mighty good time, and when they left, were presented with a gratification of two hundred and fifty dollars in shining gold coin. They concluded that this was too good for Gallegos, and belonged of right to natural-born Americans. When the Spaniards had decamped, our men came forward and volunteered. Dr. Reed accepted them, and the work went forward.