Ronald Ross Nobel Lecture

32

    1 9 0 2   R . R O S S

me to Dr. Manson (now Sir Patrick Manson). Manson, to whom the parasite

had been previously demonstrated in England, now in his turn showed it to

me; and also made me acquainted with the invaluable and illuminating mon-

ographs of Mannaberg, and of Marchiafava and Bignami. I now collected my

studies in the form of an essay (unpublished) in which I discussed the position

of the malarial problem at the time, and which was accorded the Parkes Me-

morial Prize for 1895. In November 1894, Manson communicated to me his

hypothesis, just formed by him, that the mosquito is the intermediary host

of the malaria parasite, as he had proved it to be of Filaria nocturna. I was

immediately and powerfully struck with this hypothesis, and at once deter-

mined to give it close experimental examination on my return to India. At

the same time I remembered that the same hypothesis had been mentioned by

Laveran, and I told Manson of the fact. It was not until 1899, after the solution

of the problem, that Nuttall informed me of the earlier theories of King and

Koch enunciating the same view. Consequently, I have always thought it

proper to state that my own work on that part of the malarial problem which

flowed from the mosquito theory was based on the hypothesis of Manson and

Laveran. But I do not wish by this admission to underrate those of King and

Koch; and I shall now enter upon a short digression in order to examine all

these very interesting hypotheses together.

6. The theories of King, Laveran, Koch, and Manson. 

As already mentioned, when

the malaria parasite was discovered everyone who remembered the old tel-

luric and miasmatic hypothesis thought that it must live a saprophytic exist-

ence in marshes; and up to 1894 Grassi’s Amoeba guttula was looked upon as

being possibly the free form of the organism in water. Another interpretation

of the connection between malarial fever and stagnant water had, however,

been noted as early as 1883 in a remarkable paper by King

2

. He advanced the

view that the malarial poison is carried from the marsh to the human being

by the bites of mosquitoes which breed in marshes; and he gave with great

dexterity no less than 

19 

reasons in favour of this position - reasons based en-

tirely on epidemiological considerations such as the frequency of infection in

warm moist climates, in the evening, in the lower stories of houses, etc. He

refers to a previous enunciation of this conjecture in papers by Crawford in

1807 and Nott in 1847, now apparently lost; and he quotes Manson’s filaria-

mosquito work as a reinforcement of his views; but he is evidently ignorant

of Laveran’s discovery, which was then slowly fighting its way into recogni-

tion. A fuller account of his excellent paper is given in Nuttall’s history

65,66

.

---

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

33

Laveran’s conjecture was first given briefly in 1884

3

, evidently independ-

ently of King. Seven years later he mooted the same idea, still very briefly and

without giving many reasons

11

. The similar conjecture of Koch was not pub-

lished at all; but in a letter to me he says that the mosquito theory occurred

to him during his first visit to India in the winter of 1883-1884, and that

R. Pfeiffer mentioned the matter publicly in 1892 (see Koch’s letter in sec-

tion 23).

As already stated Manson did not arrive at his hypothesis until near the end

of 1894, when he drew attention to it (after mentioning it to me) in a short

article

22

. He based it, not upon the epidemiological considerations of King,

but upon a very powerful parasitological argument of his own which was as

follows. The work of Laveran, Golgi, Marchiafava, Celli and others had clear-

Fig. 1. Gametocytes producing motile filaments; the tertian parasite (1-3); the quartian

parasite (4-6); the aestivo-autumnal parasite (7-12). From Manson’s paper, p. 644.

26

---

34

    1 9 0 2   R . R O SS

ly established that the general life-cycle of the parasites within the vertebrate

host consists of a process of schizogony or asexual spore formation, by means

of which the organisms proliferate indefinitely in the blood. But in addition

to the sporocytes existing for this purpose, all observers from the time of La-

veran had observed certain large cells, which, while they were evidently ma-

ture as regards size, did not produce spores and appeared to have no function

within the body. Laveran showed, however, that a few minutes after blood

containing these cells was withdrawn from the circulation they underwent a

singular change - that is, they gave issue to a number of long, actively motile

filaments, capable of separating themselves entirely from the parent cell, and

progressing independently among the blood corpuscles. There had already

been a long discussion about these forms. Grassi, followed by Bignami and

many other Italians, considered them to be forms of degeneration, and held

that the motile filaments were products of a kind of death agony in vitro. The

reason given for this view was that the motile filaments contain no chromatin

(which is not true); but in my opinion these observers had not considered

them with sufficient attention, or they could not have thought them to be

dying bodies. On the other hand Laveran, Danilewsky and Mannaberg, who

had studied them closely, came to the opposite conclusion that they constitute

in some way the highest stage of the parasite; and Mannaberg even conjected

that they may be concerned in the passage from the intracorporeal to the ex-

tracorporeal stage of the organisms - though he did not indicate the route by

which he thought the passage was made. Manson’s speculation broke in at

this point. He accepted Mannaberg’s position; and noted also the general law

that parasites must attain some means of passing (at least by their progeny)

from the already-infected individual into a fresh individual; that the parasites

of malaria being contained within the closed cavity of the circulation cannot

escape from it except by the intervention of some external agency (e.g. a

suctorial insect); that the position as regards these parasites was indeed the

same as that of the filaria embryos which he had shown require the interven-

tion of a mosquito to escape from the infected host; and that the epidemio-

logical laws of malarial fever suggest a possible connection with the same in-

sect. Hence it flashed upon him that the motile filaments mentioned above are

really flagellate spores, which, when the parent cells are ingested by the mos-

quito, escape and enter the insect’s tissues, developing in them into some form

analogous to that of the organisms in the human blood.

Manson continued the speculation to a further point, especially in a later

publication

26

. It will be remembered by those who have studied his works

---