Part 23 (1/2)
The inference by Dr. Reed and his a.s.sociates, from the experiments thus far made, was that yellow fever may be; transmitted by mosquitoes of the genus _Culex_, but that in order to convey the infection to a nonimmune individual the insect must be kept for twelve days or longer after it has filled itself with blood from a yellow fever patient in the earlier stages of the disease. In other words, that a certain period of incubation is required in the body of the insect before the germ reaches its salivary glands, and consequently before it is able to inoculate any individual with the germs of yellow fever. This inference, based upon experimental data, received support from other observations, which have been repeatedly made, with reference to the introduction and spread of yellow fever in localities favorable to its propagation. When a case is imported to one of our southern seaport cities, from Havana, Vera Cruz, or some other endemic focus of the disease, an interval of two weeks or more occurs before secondary cases are developed as a result of such importation. In the light of our present knowledge this is readily understood. A certain number of mosquitoes having filled themselves with blood from this first case after an interval of twelve days or more bite nonimmune individuals living in the vicinity, and these individuals after a brief period of incubation fall sick with the disease; being bitten by other mosquitoes they serve to transmit the disease through the ”intermediate host” to still others. Thus the epidemic extends, at first slowly from house to house, then more rapidly, as by geometrical progression.
It will be seen that the essential difference between the successful experiments of the board of which Dr. Reed is president and the unsuccessful experiments of Finlay consists of the length of time during which the mosquitoes were kept after filling themselves with blood from a yellow fever patient. In Finlay's experiments the interval was usually short,--from two to five or six days,--and it will be noted that in the experiments of Reed and his a.s.sociates the result was invariably negative when the insect had been kept less than eight days (7 cases).
Having obtained what they considered satisfactory evidence that yellow fever is transmitted by mosquitoes, Dr. Reed and his a.s.sociates proceeded to extend their experiments for the purpose of establis.h.i.+ng the fact in such a positive manner that the medical profession and the scientific world generally might be convinced of the reliability of the experimental evidence upon which their conclusions were based. These conclusions, which have been fully justified by their subsequent experiments, were stated in their ”Preliminary Note” as follows:
1. Bacillus icteroides (Sanarelli) stands in no causative relation to yellow fever, but, when present, should be considered as a secondary invader in this disease.
2. The mosquito serves as the intermediate host for the parasite of yellow fever.
In ”An Additional Note” read at the Pan-American Medical Congress held in Havana, Cuba, February 4,-7, 1901, a report is made of the further experiments made up to that date. In order that the absolute scientific value of these experiments may be fully appreciated I shall quote quite freely from this report with reference to the methods adopted for the purpose of excluding all sources of infection other than the mosquito inoculation:
In order to exercise perfect control over the movements of those individuals who were to be subjected to experimentation, and to avoid any other possible source of infection, a location was selected in an open and uncultivated field, about one mile from the town of Quemados, Cuba. Here an experimental sanitary station was established under the complete control of the senior member of this board. This station was named Camp Lazear, in honor of our late colleague, Dr. Jesse W. Lazear, Acting a.s.sistant Surgeon U.S.A., who died of yellow fever, while courageously investigating the causation of this disease. The site selected was well drained, freely exposed to sunlight and winds, and from every point of view satisfactory for the purposes intended.
The personnel of this camp consisted of two medical officers, Dr. Roger P. Ames, Acting a.s.sistant Surgeon U.S.A., an immune, in immediate charge; Dr. R. P. Cooke, Acting a.s.sistant Surgeon U.S.A., nonimmune; one acting hospital steward, an immune; nine privates of the hospital corps, one of whom was immune, and one immune ambulance driver.
For the quartering of this detachment, and of such nonimmune individuals as should be received for experimentation, hospital tents, properly floored, were provided. These were placed at a distance of about twenty feet from each other, and numbered 1 to 7 respectively.
Camp Lazear was established November 20, 1900, and from this date was strictly quarantined, no one being permitted to leave or enter camp except the three immune members of the detachment and the members of the board. Supplies were drawn chiefly from Columbia Barracks, and for this purpose a conveyance under the control of an immune acting hospital steward, and having an immune driver, was used.
A few Spanish immigrants recently arrived at the port of Havana were received at Camp Lazear, from time to time, while these observations were being carried out. A nonimmune person, having once left the camp, was not permitted to return to it under any circ.u.mstances whatsoever.
The temperature and pulse of all nonimmune residents were carefully recorded three times a day. Under these circ.u.mstances any infected individual entering the camp could be promptly detected and removed. As a matter of fact, only two persons, not the subject of experimentation, developed any rise of temperature; one, a Spanish immigrant, with probable commencing pulmonary tuberculosis, who was discharged at the end of three days: and the other, a Spanish immigrant, who developed a temperature of 102.6 F. on the afternoon of his fourth day in camp. He was at once removed with his entire bedding and baggage and placed in the receiving ward at Columbia Barracks. His fever, which was marked by daily intermissions for three days, subsided upon the administration of cathartics and enemata. His attack was considered to be due to intestinal irritation. He was not permitted, however, to return to the camp.
No nonimmune resident was subjected to inoculation who had not pa.s.sed in this camp the full period of incubation of yellow fever, with one exception, to be hereinafter mentioned.
For the purpose of experimentation subjects were selected as follows: From Tent No. 2, 2 nonimmunes, and from Tent No. 5, 3 nonimmunes. Later, 1 nonimmune in Tent No. 6 was also designated for inoculation.
It should be borne in mind that at the time when these inoculations were begun, there were only 12 nonimmune residents at Camp Lazear, and that 5 of those were selected for experiment, viz., 2 in Tent No. 2, and 3 in Tent No. 5. Of these we succeeded in infecting 4, viz., 1 in Tent No. 2.
and 3 in Tent No. 5, each of whom developed an attack of yellow fever within the period of incubation of this disease. The one negative result, therefore, was in Case 2--Moran--inoculated with a mosquito on the fifteenth day after the insect had bitten a case of yellow-fever on the third day. Since this mosquito failed to infect Case 4, three days after it had bitten Moran, it follows that the result could not have been otherwise than negative in the latter case. We now know, as the result of our observations, that in the case of an insect kept at room temperature during the cool weather of November, fifteen or even eighteen days would, in all probability, be too short a time to render it capable of producing the disease.
As bearing upon the source of infection, we invite attention to the period of time during which the subjects had been kept under rigid quarantine, prior to successful inoculation, which was as follows: Case 1, fifteen days; Case 3, nine days; Case 4, nineteen days; Case 5, twenty-one days. We further desire to emphasize the fact that this epidemic of yellow fever, which affected 33.33 per cent of the nonimmune residents of Camp Lazear, did not concern the seven nonimmunes occupying Tents Nos, 1, 4, 6 and 7, _but was strictly limited to those individuals who had been bitten by contaminated mosquitoes._
Nothing could point more forcibly to the source of this infection than the order of the occurrence of events at this camp. The precision with which the infection of the individual followed the bite of the mosquito left nothing to be desired in order to fulfill the requirements of a scientific experiment.
In summing up their results at the conclusion of this report the following statement is made:
Out of a total or eighteen nonimmunes whom we have inoculated with contaminated mosquitoes, since we began this line of investigation, eight, or 44.4 per cent, have contracted yellow fever. If we exclude those individuals bitten by mosquitoes that had been kept less than twelve days after contamination, and which were therefore probably incapable of conveying the disease, we have to record eight positive and two negative results--80 per cent.
In a still later report (May, 1901) Dr. Reed says, ”We have thus far succeeded in conveying yellow fever to twelve individuals by means of the bites of contaminated mosquitoes.”
The nonimmune individuals experimented upon were all fully informed as to the nature of the experiment and its probable results and all gave their full consent. Fortunately no one of these brave volunteers in the cause of science and humanity suffered a fatal attack of the disease, although several were very ill and gave great anxiety to the members of the board, who fully appreciated the grave responsibility which rested upon them. That these experiments were justifiable under the circ.u.mstances mentioned is, I believe, beyond question. In no other way could the fact established have been demonstrated, and the knowledge gained is of inestimable value as a guide to reliable measures of prevention. Already it is being applied in Cuba, and without doubt innumerable lives will be saved as a result of these experiments showing the precise method by which yellow fever is contracted by those exposed in an ”infected locality.” Some of these volunteers were enlisted men of the United States Army and some were Spanish immigrants who had recently arrived in Cuba. When taken sick they received the best possible care, and after their recovery they had the advantage of being ”immunes” who had nothing further to fear from the disease which has caused the death of thousands and tens of thousands of Spanish soldiers and immigrants who have come to Cuba under the orders of their government or to seek their fortunes.
The experiments already referred to show in the most conclusive manner that the blood of yellow fever patients contains the infectious agent, or germ, to which the disease is due, and this has been further demonstrated by direct inoculations from man to man. This experiment was made by Dr. Reed at ”Camp Lazear” upon four individuals, who freely consented to it; and in three of the four a typical attack of yellow fever resulted from the blood injection. The blood was taken from a vein at the bend of the elbow on the first or second day of sickness and was injected subcutaneously into the four nonimmune individuals, the amount being in one positive case 2 cc, in one 1.5 cc, and in one O.5 cc. In the case attended with a negative result, a Spanish immigrant, a mosquito inoculation also proved to be without effect, and Dr. Reed supposes that this individual ”probably possesses a natural immunity to yellow fever.” Dr. Reed says with reference to these experiments:
It is important to note that in the three cases in which the injection of the blood brought about an attack of yellow fever, careful culture from the same blood, taken immediately after injection, failed to show the presence of Sanarelli's bacillus.
Having demonstrated the fact that yellow fever is propagated by mosquitoes, Dr. Reed and his a.s.sociates have endeavored to ascertain whether it may also be propagated, as has been commonly supposed, by clothing, bedding, and other articles which have been in use by those sick with this disease. With reference to the experiments made for the solution of this question I cannot do better than to quote _in extensa_ from Dr. Reed's paper read at the Pan-American Medical Congress in Havana.
[This extract from Dr. Reed's paper describes in careful scientific detail the experiments which finally established the fact that the contagion came through mosquitoes, and in no other way. Into a small house, thoroughly air-proof, were brought bedclothes, clothing, and other articles which had been contaminated by yellow fever patients.
Then for twenty days men who were nonimmune to the fever slept in this building, with no evil effects. This experiment was repeated several times. Then in another building similar, except that it was ventilated by mosquito-proof windows, and had been thoroughly disinfected, another volunteer was bitten by mosquitoes which had first bitten patients suffering with yellow fever; and he developed the disease. The last paragraph of the extract is as follows:]