Ronald Ross Nobel Lecture

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

39

pared for the microscope), and was known to occur in from about 

10 

to 30

minutes after the blood is drawn from the patient; but it was now necessary

to follow it in the mosquito. The insects were killed from one minute to sev-

eral hours after feeding, the stomach being then extracted and its contents ex-

amined in the fresh state. I was obliged to invent the technique for myself; and

my first successful dissection was made on the 13th May. Within a few weeks

I made a fairly complete study of the subject and ascertained an encouraging

fact. In vitro, doubtless owing to the unnatural conditions, only about five per

cent of the crescents give issue to the motile filaments; but I now found that

in the mosquito’s stomach something like sixty per cent of them do so. It was

also noted that the preliminary stages of the process, namely the swelling up

and rounding of the crescents, were much more constantly seen in the blood

ingested by the insect than in vitro. This was of importance because it showed

at least that the insect’s stomach is a more favourable locus for the process than

an ordinary specimen of blood is. I observed also that a considerable percent-

age of the crescents (about one-third) never produced motile filaments at all,*

even after the lapse of several hours and within the insects; and I noticed that

those which refused to emit them had a slightly different appearance to the

others. At the time I thought that they were parasites which had been killed

in some manner during ingestion; but when I repeated the experiments next

year I saw cause to doubt this, and felt some difficulty in explaining why all

the crescents did not emit filaments as they should have done according to

Manson’s hypothesis regarding their nature.

A description of these first results was written in June, but was not published

until the end of the year

24

.

10. Difficulty of the task. New

 methods devised. The fact, then, was established

that the gametocytes are not immediately killed in the mosquito’s stomach

(as might well have happened), but indeed emit their motile filaments more

readily there than in vitro. It was necessary now to seek the destination of the

latter in the insect’s tissues; and here the true magnitude of the task to which

I had set myself became manifest. Manson had been able to follow the migra-

tions of the filaria embryos with comparative ease because they are large or-

ganisms readily distinguishable from the fluids or tissues which surround

them. But the motile filaments are exceedingly delicate bodies, the move-

ments of which are very difficult to follow even with the highest powers of a

* It was easy to distinguish those which had produced the filaments by their collapsed

condition afterwards.

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40

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good microscope and in the clear spaces of an ordinary preparation of blood.

But the blood in a mosquito’s stomach shortly becomes a thick grumous mass

in which it is impossible even to see the filaments unless they are in active

movement. Moreover, even this assistance was denied me; for I speedily ascer-

tained that within a few minutes of their escape they seemed to lose their

movements. At least they constantly disappeared as if by magic; and in spite

of all artifices I failed to ascertain what had become of them.* In fact to trace

them further, to follow the migrations of these well-nigh invisible bodies

through the masses of cells of which so large an animal as a mosquito is com-

posed was indeed an impossible task with the means which I possessed.

Hence, though Manson then and later constantly advised me in his letters to

adhere to the plan of following the motile filaments, I determined to abandon

the quest and to emply other methods; and he himself failed to obtain any

results with the insects which I sent to him from time to time. It was most

fortunate that I came to this decision so early, because events have proved that

the motile filaments migrate nowhere, and do not enter the mosquito’s tissues

at all.

The first method which I now adopted and which ultimately led to success

was the following. By hypothesis, the motile filaments after reaching the par-

ticular cells of the mosquito for which we thought they were destined, should

grow in them into some unknown but larger form. It was impossible to pre-

dict what this form would be. Manson conjectured that it would very likely

be some intracellular form similar to the intracorpuscular stages of the organ-

ism in the human blood - fixed perhaps in the stomach cells or blood cells of

the insect. Personally, however, while I thought this view possible, I had no

full faith in it. It seemed to me that the mosquito stage of the parasite might

be anything, so long as it was of a protozoal character.

The protean changes of many of the parasitic worms warned us that nature

was capable of ordering any extraordinary transformations in the interest of

parasites; and as no case was yet known of a protozoon capable of wandering

from one species of host to another, I had no guide as to what might happen

with the organisms which I was studyin g, and conjectured that for all we

could say, the motile filaments might develop into almost any form - amoe-

boid, coccidiform, gregarinoid, or even infusorial, small or large. What was

nearly certain, however, was that they were likely to grow in size after a few

* It might now be possible, though still difficult, to follow them by staining them either

in dehaemoglobinized blood or in section; but the Romanowsky reaction was not known

to me at that time.

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