Ronald Ross Nobel Lecture

    R E S E A R C H E S   O N   M A L A R I A

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days’ residence in the mosquito - to become more visible, and, if they were to

pass into the water as we thought they would do, to take a definite form of

resistance which ought to be easily recognizable. My new method then was to

give up the attempt to follow the newly escaped and almost invisible motile

filaments, and to dissect the mosquitoes, not at once, but after the lapse of

some days, during which time the motile filaments should by hypothesis de-

velop into something more tangible. I proposed then to feed the mosquitoes

as before on cases with crescents in the blood; to keep them alive for some

days; and then search their tissues for any parasites which might occur in them.

The parasites found, it would be easy to determine whether or not they are

derived from the motile filaments, simply by ascertaining whether or not they

also occur in mosquitoes of the same kind fed on healthy blood. Throughout

the investigation it was of course necessary to employ only what I called in

bacteriological parlance "sterile mosquitoes", that is mosquitoes freshly hatch-

ed from the larvae in captivity and therefore not contaminated by previous

feedings.

Such was the procedure now adopted; but the difficulties involved even in

it were very great. As the situation of the sought-for parasites could not be

indicated with any certainty, it became necessary to search for them through

all the tissues of each insect examined - to scrutinize by a powerful micro-

scope, one by one, all the minute cells composing the huge aggregate of which

the insect consists.* To investigate a single insect thoroughly in this manner

required at least two hours’ exhausting and blinding work. Added to this dif-

ficulty, I had no clue as to the form and appearance of the object which I was

seeking for; nor was I even sure that the kind of insect under examination was

amenable to the infection at all. I was looking for a thing of which I did not

know the appearance in a medium which I did not know contained it. In short

it was a mere blind groping for some clue which I trusted fortune would give

in the end. As an instance of the difficulty of such work I may mention that

neither the organisms of yellow fever, which is now known to exist in a par-

ticular kind of mosquito, nor the Pyrosoma of Texas cattle-fever, which is

known to exist in a tick, have yet been found in these animals, though long

searched for by competent observers. Nevertheless, I am confident that, hope-

less as the method may appear, it was the only one capable of solving this

difficult problem.

At the outset of the investigation it was necessary for me to become thor-

oughly acquainted with the normal histology of the mosquito - for which I

* Under a magnification of a thousand diameters a mosquito appears as large as a horse.

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had again to trust to my own observation; in spite of all efforts no literature

on the subject could be obtained by me. It was also necessary to note and study

the ordinary parasites of these insects - of which I found a number during the

ensuing years. Indeed, at the commencement of the work I found one which

required careful working out. It was a pseudo-navicella occurring in the mal-

pighian tubes of the brindled mosquitoes (Stegomyia). After a little study it

was ascertained that pseudo-navicellae have no connection with the parasites

of malaria, being the sporocysts of a species of gregarine. Next year Manson

published an account of these interesting organisms taken from my letters to

him

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. I refer to them also in my publication at the end of the year

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.

The second method alluded to above was based on the following considera-

tions. According to Manson’s more advanced hypothesis, the motile fila-

ments, after living some days in the mosquito, would probably pass from it

into the water, on the surface of which we then supposed it usually died after

laying its eggs. Such water then ought to be infective to human beings, either

when ingested, or perhaps when inhaled as a vapour. It would be easy to test

this speculation by experiment. I caused a number of mosquitoes, both of the

brindled and grey varieties, to feed on a selected patient, and then kept them

in large jars containing water at the bottom, until they died one by one. The

water was then exposed to sunlight and otherwise allowed to remain in the

condition of marsh water. Different batches of fed mosquitoes were intro-

duced into the jars from time to time so as to make sure that the water should

indeed contain the parasites which by hypothesis should escape from the in-

sects. In May 1895 I gave draughts of this water to three natives who volun-

teered themselves for the experiment. All of them declared that they had not

suffered from fever for years.* Strangely enough one of the men developed a

mild but marked attack of fever in eleven days, the parasite being found in his

blood. I was naturally much pleased with the success of the experiment and

began to hope that the mode of infection had been found; but the failure of

many subsequent attempts of the same kind forced me later to reject any defi-

nite conclusion on the point (section 11).**

11. Bangalore (1895-1897). Progress of

 work. Possessing abundance of material

* The experiment was justifiable owing to the slight degree of illness usually produced

by malarial fever in natives when properly treated.

** Owing to the interest of Surgeon Major Owen, the Maharajah of Patiala had at this

time offered the government of the Punjab to employ me at his own expense to study ma-

laria in his dominions. The government of the Punjab, however, refused the offer.

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