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.
* * * * *
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.