Ronald Ross Nobel Lecture

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

45

test this view immediately by experiment; and early in August I made a small

series of observations which were published in the same paper

30

.

A number of mosquitoes all bred from larvae in captivity, and of all the

kinds which I could collect (many specimens of brindled and grey mosqui-

toes) were fed upon several patients with numerous parasites in their blood.

One of these patients had all three kinds of parasites in him; and I specially

employed this case, as well as many varieties of mosquitoes, in order to in-

crease the chances of one at least of the species of mosquitoes present being

appropriate for one at least of the species of parasites. After feeding, the insects

were kept alive for one or two days and were then applied in considerable

numbers on two occasions to Mr. Appia, Assistant Surgeon of the Bowring

Civil Hospital at Bangalore, who courageously volunteered for the experi-

ment. Mr. Appia had suffered from malarial fever some years previously, but

not since then; so that if he should be attacked by fever shortly after the ex-

periment, it would be strong evidence, if not proof, in favour of the inocula-

tion theory. He remained, however, absolutely free from fever. He was then

bitten by five mosquitoes which had been partially fed immediately before on a

case of crescents - on the supposition that the insects may carry the infection

mechanically, as the tsetse fly carries nagana; but the result was again negative.

Lastly two other individuals were bitten by mosquitoes fed from three to five

days previously; still without effect. I judged then, either that infection is not

produced in this way, or that the proper species of mosquitoes had not been

employed, or that they had not been kept for the proper period after feeding;

and I proposed to return to the subject again. It should be noted that these

experiments of mine were made quite independently, and before I had heard

of the theories of King and Bignami - as indeed was stated in another publica-

tion of mine at the end the year

32

.

In July 1896 Bignami’s criticism of Manson’s hypothesis, referred to in sec-

tion 6, appeared in Italy

29

. I heard nothing about it whatever, until I received

Manson’s letter of the 12th October, which was accompanied by a translation

of the critique. Bignami’s paper was not a profound one, and consisted only of

a copious and dexterous rendering of ideas which were new only to those who

had not already fully considered the subject. His objection to Manson’s theory

was based principally on Grassi’s loose speculation that the motile filaments

are the result of the death of the parasites in vitro. As this was a vital point in

the chain of reasoning I now set to work to examine the subject experiment-

ally, and was soon able to show that the escape of the filaments depends on

certain proper conditions, and not at all on the death of the parasites. Thus

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they escape more readily when the specific gravity of the blood is altered,

either by the abstraction of water by partial evaporation or, as Marshall prov-

ed, by the addition of a little water. On the other hand they do not escape at

all, even when the parent cells perish, so long as the blood is kept scrupulously

unchanged. In order to prove this, I drew the blood from the finger into a

small mass of Vaseline placed upon the skin, and then mounted the whole for

the microscope in such a manner as to prevent the blood coming even into

momentary contact with the air. The result was that not a single crescent

emitted motile filaments or even underwent the preliminary change of spher-

utilization, although it was evident they all died after a time.* This experiment

completely disposed of the death-agony theory of the Italians. Previously to

this, however, Sacharoff had shown that contrary to Grassi’s statements, the

filaments do contain chromatin; but I could not procure a copy of his work

32

.

I should add that after long observation of the filaments I could never bring

myself to believe that they are merely the result of the spasmodic movements

of dying protoplasm; and this tale was in fact never anything but a gratuitous

assumption.

These researches were published later

32,33

, and were confirmed by Manson

and Rees in London

37

.

The conditions required by the crescents for emitting filaments were now

clearly seen to be those obtaining in the mosquito’s stomach, where the blood

is rapidly altered by abstraction of water; and I therefore continued my work

without further reference to Bignami’s objection.

His view that infection may be caused by inoculation had already been con-

sidered and experimented on by me, as just mentioned. But it should be under-

stood that Bignami’s hypothesis (which was the same as that given long pre-

viously and much more strongly by King) was very different from mine.

King and Bignami thought that mosquitoes bring the poison from marshes to

man; this speculation had not occurred to me until I read Bignami’s paper in

October, and then it did not appeal to me at all, because it was self-evident

that the connection between malaria and marshes could be sufficiently ex-

plained by the fact that mosquitoes breed in stagnant water. My speculation

was that mosquitoes become infected from men (according to Manson’s in-

* If the preparation was opened and the blood momentarily exposed to the air within

some hours after abstraction from the patient, the crescents could be seen at once to re-

sume their functions. But if this experiment was delayed about 24 hours, the crescents no

longer reacted, and indeed showed clear evidence of death by their vacuolization and

other structural changes.

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