at once checking the propagation of the disease.
On the first day of August the board met and after due
deliberation determined to investigate mosquitoes in connection
with the spread of yellow fever. As Dr. Lazear was the only one
of us who had had any experience in mosquito work, Major Reed
thought proper that he should take charge of this part of the
investigation in the beginning, while we, Carroll and I,
continued with the other work on hand, at the same time
gradually becoming familiar with the manipulations necessary in
dealing with the insects.
A visit was now made to Dr. Finlay, who, much elated at the
news that the board was about to investigate his pet theory,
the transmission of yellow fever from man to man by mosquitoes,
very kindly explained to us many points regarding the life of
the one kind he thought most guilty and ended by furnishing us
with a number of eggs which, laid by a female mosquito nearly a
month before, had remained unhatched on the inside of a half
empty bowl of water in his library.
Much to our disappointment and regret, during the first week of
August, Major Reed was recalled to Washington that he might, in
collaboration with Drs. Vaughan and Shakespeare, complete the
report upon "Typhoid Fever in the Army." Thus we were deprived
of his able counsel during the first part of the mosquito
research. Major Reed was detained longer than he expected and
could not return to Cuba until early in October, several days
after Lazear's death.
The mosquito eggs obtained from Dr. Finlay hatched out in due
time; the insects sent to Washington for their exact
classification were declared by Dr. L. O. Howard, entomologist
to the Agricultural Department, to be Culex fasciatus. Later,
they have been called Stegomyia fasciatus and now go under the
name of Stegomyia calopus (Aedes cal.).
Lazear applied some of these mosquitoes to cases of yellow
fever at "Las Animas" Hospital, keeping them in separate glass
tubes properly labeled, and every thing connected with their
bitings was carefully recorded; the original batch soon died
and the work was carried on with subsequent generations from
the same.
The lack of material at Quemados caused us to remove our field
of action to Havana, where cases of yellow fever continued to
appear. We met almost every day at "Las Animas" Hospital, where
Lazear was trying to infect his mosquitoes, or now and then I
performed autopsy upon a case, and Carroll secured sufficient
cultures to last him for several days of bacteriological
investigation.
Considering that, in case our surmise as to the insect's action
should prove to be correct, it was dangerous to introduce
infected mosquitoes amongst a population of 1,400 non-immunes
at Camp Columbia, Dr. Lazear thought best to keep his
presumably infected insects in my laboratory at the Military
Hospital No. 1, from where he carried them back and forth to
the patients who were periodically bitten.
Incidentally, after the mosquitoes fed upon the yellow fever
patients, they were applied, at intervals of two or three days,
to whoever would consent to run the risk of contracting yellow
fever in this way; needless to say, current opinion was against
this probability and as time passed and numerous individuals
who had been bitten by insects which had previously fed upon
yellow fever blood remained unaffected, I must confess that
even the members of the board, who were rather sanguine in
their expectations, became somewhat discouraged and their faith
in success very much shaken.
No secret was made of our attempts to infect mosquitoes; in
fact many local physicians became intensely interested, and
Lazear and his tubes were the subject of much comment on the
part of the Havana doctors, who nearly twenty years before had
watched and laughed at Dr. Finlay, then bent apparently upon
the same quest in which we were now engaged. Dr. Finlay himself
was somewhat chagrined when he learned of our failure to infect
any one with mosquitoes, but, like a true believer, was
inclined to attribute this negative result more to some defect
in our technique than to any flaw in his favorite theory.
Although the board had thought proper to run the same risks, if
any, as those who willingly and knowingly subjected themselves
to the bites of the supposedly infected insects, opportunity
did not offer itself readily, since Major Reed was away in
Washington and Carroll, at Camp Columbia, engrossed in his
bacteriological investigations came to Havana only when an
autopsy was on hand or a particularly interesting case came up
for study. I was considered an immune, a fact that I would not
like to have tested, for though born in the island of Cuba, I
had practically lived all my life away from a yellow fever
zone; it was therefore presumed that I ran no risk in allowing
mosquitoes to bite me, as I frequently did, just to feed them
blood, whether they had previously sucked from yellow fever
cases or not. And so, time passed and several Americans and
Spaniards had subjected themselves in a sporting mood to be
bitten by the infected (?) mosquitoes without causing any
untoward results, when Lazear applied to himself (August 16,
1900) a mosquito which ten days before had fed upon a mild case
of yellow fever in the fifth day of his disease; the fact that
no infection resulted, for Lazear continued in excellent health
for a space of time far beyond the usual period of incubation,
served to discredit the mosquito theory in the opinion of the
investigators to a degree almost beyond redemption, and the
most enthusiastic, Dr. Lazear himself, was almost ready to
"throw up the sponge."
I had as laboratory attendant a young American, a private
belonging to the Hospital Corps of the Army, who more than once
had bared his arm to allow a weak mosquito a fair meal with
which to regain its apparently waning strength; Loud, for that
was his name, derided the idea that such a little beast could
do so much harm as we seemed ready to accuse it of, although he
was familiar with the destruction caused by bacteria, but then,
he used to say, "bacterial work in armies of more than a
million bugs at the same time and no one would be d---- fool
enough to let more than one or two gnats sting him at once."
This state of things, the gradual loss of faith in the danger
which mosquitoes seemed to possess, led Dr. Lazear to relax a
little and become less scrupulous in his care of the insects,
and often, after applying them to patients, if pressed for
time, he would take them away with him to his laboratory at
Columbia Barracks, where, the season being then quite warm,
they could be kept as comfortably as at the Military Hospital
laboratory. Thus it happened that on the twenty-seventh of
August he had spent the whole morning at "Las Animas" Hospital
getting his mosquitoes to take yellow-fever blood: the
procedure was very simple; each insect was contained in a glass
tube covered by a wad of cotton, the same as is done with
bacterial cultures. As the mouth of the tube is turned
downwards, the insect usually flies towards the bottom of the
tube (upwards), then the latter is uncovered rapidly and the
open mouth placed upon the forearm or the abdomen of the
patient; after a few moments the mosquito drops upon the skin
and if hungry will immediately start operations; when full, by
gently shaking the tube, the insect is made to fly upwards
again and the cotton plug replaced without difficulty. It so
happened that this rather tedious work, on the day above
mentioned, lasted until nearly the noon hour, so that Lazear,
instead of leaving the tubes at the Military Hospital, took
them all with him to Camp Columbia: among them was one insect
that for some reason or other had failed to take blood when
offered to it at "Las Animas" Hospital.
This mosquito had been hatched in the laboratory and in due
time fed upon yellow-fever blood from a severe case on August
15, that is, twelve days before, the patient then being in the
second day of his illness; also at three other times, six days,
four days and two days before. Of course, at the time, no
particular attention had been drawn to this insect, except that
it refused to suck blood when tempted that morning.
After luncheon that day, as Carroll and Lazear were in the
laboratory attending to their respective work, the conversation
turning upon the mosquitoes and their apparent harmlessness,
Lazear remarked how one of them had failed to take blood, at
which Carroll thought that he might try to feed it, as
otherwise it was liable to die before next day (the insect
seemed weak and tired); the tube was carefully held first by
Lazear and then by Carroll himself, for a considerable length
of time, upon his forearm, before the mosquito decided to
introduce its proboscis.
This insect was again fed from a yellow fever case at "Las
Animas" Hospital on the twenty-ninth, two days later, Dr.
Carroll being present, though not feeling very well, as it was
afterwards ascertained.
We three left the yellow-fever hospital together that
afternoon; I got down from the doherty-wagon where the road
forks, going on to the Military Hospital, while Carroll and
Lazear continued on their way to Camp Columbia. On the
following day, Lazear telephoned to me in the evening, to say
that Carroll was down with a chill after a sea bath taken at
the beach, a mile and a half from Camp, and that they suspected
he had malaria; we therefore made an appointment to examine his
blood together the following morning.
When I reached Camp Columbia I found that Carroll had been
examining his own blood early that morning, not finding any
malarial parasites; he told me he thought he had "caught cold"
at the beach: his suffused face, blood-shot eyes and general
appearance, in spite of his efforts at gaiety and unconcern,
shocked me beyond words. The possibility of his having yellow
fever did not occur to him just then; when it did, two days
later, he declared he must have caught it at my autopsy room in
the Military Hospital, or at "Las Animas" Hospital, where he
had been two days before taking sick. Although we insisted that
he should go to bed in his quarters, we could only get him to
rest upon a lounge, until the afternoon, when he felt too sick
and had to take to his bed.
Lazear and I were almost panic-stricken when we realized that
Carroll had yellow fever. We searched for all possibilities
that might throw the blame for his infection upon any other
source than the mosquito which bit him four days before;
Lazear, poor fellow, in his desire to exculpate himself, as he
related to me the details of Carroll's mosquito experiment,
repeatedly mentioned the fact that he himself had been bitten
two weeks before without any effect therefrom and finally, what
seemed to relieve his mind to some extent, was the thought that
Carroll offered himself to feed the mosquito and that he held
the tube upon his own arm until the work was consummated.
I have mentioned before that, as Lazear and I, vaguely hoping
to find malarial parasites in Carroll's blood, sat looking into
our microscopes that morning, the idea that the mosquito was
what brought him down gradually took hold of our minds, but as
our colleague had been exposed to infection in other ways, by
visiting the yellow fever hospital "Las Animas," as well as the
infected city of Havana, it was necessary to subject that same
mosquito to another test and hence the inoculation of Private
Dean, which is described in the opening chapter of this
history.
TERMINATION OF THE FIRST SERIES OF MOSQUITO EXPERIMENTS.
DEATH OF LAZEAR.
The month of September, 1900, was fraught with worry and
anxiety: what with Carroll's and Private Dean's attacks of
yellow fever and Major Reed's inability to return, Lazear and I
were well-nigh on the verge of distraction. Private Dean was
not married, but Carroll's wife and children, a thousand miles
away, awaited in the greatest anguish the daily cablegram which
told them the condition of the husband and father, who was
fighting for life, sometimes the victim of the wildest delirium
caused by consuming fever, at others almost about to collapse,
until one day, the worst of the disease being over, the wires
must have thrilled at our announcement, "Carroll out of
danger."
Fortunately both he and Dean made an uninterrupted recovery,
but we were still to undergo the severest trial, a sorrow
compared to which the fearful days of Carroll's sickness lose
all importance and dwindle almost into insignificance.
On the morning of the eighteenth my friend and classmate
Lazear, whom in spite of our short intercourse I had learned to
respect and in every way appreciate most highly, complained
that he was feeling "out of sorts." He remained all day about
the officers' quarters and that night suffered a moderate
chill. I saw him the next day with all the signs of a severe
attack of yellow fever.
Carroll was already walking about, though enfeebled by his late
sickness, and we both plied Lazear with questions as to the
origin of his trouble; I believe we affectionately chided him
for not having taken better care of himself. Lazear assured us
that he had not experimented upon himself, that is, that he had
not been bitten by any of the purposely infected mosquitoes.
After the case of Dean so plainly demonstrated the certainty of
mosquito infection, we had agreed not to tempt fate by trying
any more upon ourselves, and even I determined that no mosquito
should bite me if I could prevent it, since the subject of my
immunity was one that could not be sustained on scientific
grounds; at the same time, we felt that we had been called upon
to accomplish such work as did not justify our taking risks
which then seemed really unnecessary. This we impressed upon
Major Reed when he joined us in October and for this reason he
was never bitten by infected mosquitoes.
Lazear told us, however, that while at "Las Animas" Hospital
the previous Thursday (five days before), as he was holding a
test-tube with a mosquito upon a man's abdomen, some other
insect which was flying about the room rested upon his hand; at
first, he said, he was tempted to frighten it away, but, as it
had settled before he had time to notice it, he decided to let
it fill and then capture it; besides, he did not want to move
in fear of disturbing the insect contained in his tube, which
was feeding voraciously. Before Lazear could prevent it, the
mosquito that bit him on the hand had flown away. He told us in
his lucid moments, that, although Carroll's and Dean's cases
had convinced him of the mosquito's role in transmitting yellow
fever, the fact that no infection had resulted from his own
inoculation the month before had led him to believe himself, to
a certain extent, immune.
How can I describe the agony of suspense which racked our souls
during those six days? It seemed to us as though a life was
being offered in sacrifice for the thousands which it was to
contribute in saving. Across the span of thirteen years the
memory of the last moments comes to me most vividly and
thrilling, when the light of reason left his brain and shut out
of his mind the torturing thought of the loving wife and
daughter far away, and of the unborn child who was to find
itself fatherless on coming to the world.
Tuesday, the twenty-fifth of September saw the end of a life
full of promise; one more name, that of Jesse W. Lazear, was
graven upon the portals of immortality. And we may feel justly
proud for having had it, in any way, associated with our own.
The state of mind in which this calamity left us may better be
imagined than described. The arrival of Major Reed several days
after in a great measure came to relieve the tensity of our
nerves and render us a degree of moral support of which we were
sorely in need.
Lazear's death naturally served to dampen our fruition at the
success of the mosquito experiments, but, this notwithstanding,
when the facts were known we were the subjects of much
congratulation and the question whether the theory had been
definitely demonstrated or not was the theme of conversation
everywhere, about Havana and Camp Columbia particularly. We
fully realized that three cases, two experimental and one
accidental, were not sufficient proof, and that the medical
world was sure to look with doubt upon any opinion based on
such meager evidence; besides, in the case of Carroll, we had
been unable to exclude the possibility of other means of
infection, so that we really had but one case, Dean's, that we
could present as clearly demonstrative and beyond question. In
spite of this, we thought that the results warranted their
presentation in the shape of a "Preliminary Note," and after
all the data were carefully collected from Lazear's records and
those at the Military Hospital, a short paper was prepared
which the Major had the privilege to read at the meeting of the
American Public Health Association, held on October 24, in the
city of Indianapolis.
For this purpose Major Reed went to the States two weeks after
his return to Cuba, and Carroll also took a short leave of
absence so as to fully recuperate, in preparation for the
second series of inoculations which we had arranged to
undertake, after the Indianapolis meeting.
These inoculations, according to our program, were to be made
upon volunteers who should consent to suffer a period of
previous quarantine at some place to be selected in due time,
away from any possibility of yellow fever.
It so happened then that I was left the only member of the
board in Cuba and, under instructions from Major Reed, I began
to breed mosquitoes and infect them, as Lazear used to do,
wherever cases occurred, keeping them at my laboratory in the
Military Hospital No. 1. Major Reed had also asked me to look
about for a proper location wherein to continue the work upon
his return.
ORIGIN AND DEVELOPMENT OF THE MOSQUITO THEORY
The possible agency of insects in the propagation of yellow
fever was thought of by more than one observer, from a very
early period in the history of this disease. For instance,
Rush, of Philadelphia, in 1797, noticed the excessive abundance
of mosquitoes during that awful epidemic. Subsequently, several
others spoke of the coincidence of gnats or mosquitoes and
yellow fever, but without ascribing any direct relation to the
one regarding the other. Of course, man-to-man infection
through the sole intervention of an insect was a thing entirely
inconceivable and therefore unthought of until very recently,
and in truth the discovery, as far as yellow fever is
concerned, was the result of a slow process of evolution of the
fundamental fact, taken in connection with similar findings, in
other diseases.
The earliest direct reference is found in the writings of Dr.
Nott, of Mobile, Ala., who in 1848 suggested that the
dissemination of the yellow fever poison was evidently by means
of some insect "that remained very close to the ground." But
the first who positively pointed to the mosquito as the
spreader of yellow fever, who showed that absence of mosquitoes
precluded the existence of the disease and who prescribed the
ready means to stamp it out, by fumigation and by preventing
the bites of the insects, was Dr. Louis D. Beauperthuy, a
French physician, then located in Venezuela. The writer has an
original copy of his paper, published in 1853, where he fastens
the guilt upon the domestic mosquitoes, believing, in accord
with the prevailing teachings of medical science, that the
mosquitoes infected themselves by contact or feeding upon the
organic matter found in the stagnant waters where they are
hatched, afterwards inoculating the victims by their sting. He
recognized the fact that yellow fever is not contagious and
therefore could not think of the possibility of man-to-man
infection, as we know it to-day. The keenest observer was this
man Beauperthuy, and, even at that benighted time in the
history of tropical medicine, made most interesting studies of
the blood and tissues, employing the microscope and the
chemical reactions in his research. No one believed him, and a
commission appointed to report upon his views said that they
were inadmissible and all but declared him insane.
This field of investigation remained dormant for a
comparatively long period of time. Meanwhile another medical
writer, Dr. Greenville Dowell, mentions in 1876, that "if we
compare the effect of heat and cold on gnats and mosquitoes
with yellow fever, it will be difficult to believe it is of the
same nature, as it is controlled by the same natural laws."
Soon after this, in 1879, the first conclusive proof of the
direct transmission of a disease from man-to-man was presented
by the father of tropical medicine, Sir Patrick Manson, with
regard to filaria, a blood infection that often causes the
repulsive condition known as elephantiasis and which the
mosquito takes from man and after a short time gives over to
another subject. This discovery attracted world-wide attention
and many looked again towards the innumerable species of biting
insects that dwell in the Tropic Zone, as possible carriers of
the obscure diseases which also prevail in those regions.
In 1881, Dr. Carlos Finlay, of Havana, in an exhaustive paper
read before the Royal Academy of Sciences, gave as his opinion
that yellow fever was spread by the bites of mosquitoes
"directly contaminated by stinging a yellow fever patient (or
perhaps by contact with or feeding from his discharge)." This
latter view he held as late as 1900, which, although correct in
the main fact of the transmission of the germ from a patient to
a susceptible person by the mosquito, the modus operandi, as he
conceived it, was entirely erroneous.
Dr. Finlay, unfortunately was unable to produce experimentally
a single case of fever that could withstand the mildest
criticism, so that at the time when the Army Board came to
investigate the causes of yellow fever in Cuba, his theory,
though practically the correct one, had been so much
discredited, in a great measure by his own failures, that the
best-known experts considered it as an ingenious, but wholly
fanciful, one and many thought it a fit subject for humorous
and sarcastic repartee. Finlay also believed, erroneously, that
repeated bites of contaminated insects might protect against
yellow fever and that the mosquitoes were capable of
transmitting the germ to the next generation.
The wonderful discoveries of Theobald Smith, as to the agency
of ticks in spreading Texas fever of cattle, and those of Ross
and the Italian investigators who showed conclusively that
malaria was transmitted by a species of mosquito, brought the
knowledge of these various diseases to the point where the Army
Board took up the investigation of yellow fever.
SECOND AND FINAL SERIES OF MOSQUITO EXPERIMENTS
Major Reed came back to Havana in the early part of November,
Carroll following a week after.
During their absence, I had been applying mosquitoes to yellow
fever patients at "Las Animas" Hospital, keeping them in my
laboratory, as it was done at the beginning of the
investigation; the season being more advanced, now and then a
cold "norther" would blow and my insects suffered very much
thereby, so that I had the greatest trouble in preventing their
untimely death: to this may be added the difficulty met in
feeding them blood, for now that I knew their sting was
dangerous, unto death perhaps, I could not allow any
indiscriminate biting, but had to select for the purpose
individuals who had suffered an attack of the disease and were
therefore immune.
The necessity for an experimental camp became more imperative
as time passed, not only where proper quarantine and isolation
could be established, but also where the insects intended for
the inoculations might receive better care. This entailed
considerable expense.