270 



NATURE 



[November 5, 1914 



remembered that Laveran had said the same thing ; 

 but I was not aware of King's paper, or of the 

 remarkable researches on Piroplasma by Smith and 

 Kilborne. 



In 1895 I attacked the work experimentally at 

 Secunderabad in India, and determined first to adopt 

 the mosquito speculation as a working hypothesis, 

 and then to study other hypotheses if it failed — though 

 I was much impressed by the former. The whole 

 history of my work has been full)' given in my Nobel 

 Lecture, published in England by the Journal of the 

 Royal Army Medical Corps (1905); and I need mention 

 here only the salient points. For more than two 

 years I caused mosquitoes of the genera Culex and 

 Stegomyia to feed on patients containing malaria 

 '■ crescents," which were the proper forms for trans- 

 mission according to Manson. But my failure was 

 complete, and indeed it was impossible to follow what 

 he thought were flagellated spores in the insect's 

 tissues. 



I then adopted another technique, which was to 

 compare insects of the same species which had been 

 fed on malarial blood with those which had not been 

 so fed, and to see if I could find any particular para- 

 sites in the former after they had been kept alive for 

 some days. Many hundreds of insects were studied 

 completely in this manner, and more than a thousand 

 incompletely ; but my failure was still complete. I 

 obtained, however, a close practical experience of the 

 insect's tissues, and learnt much about some common 

 parasites which they possess. I also endeavoured to 

 infect healthy persons by means of water in which 

 presumably infected mosquitoes had been allowed to 

 die, as Manson thought that such water would infect ; 

 and, lastly, I worked at a hypothesis of mine, that 

 infected mosquitoes might carr}- infection by their 

 bites, and Mr. Appia, assistant-surgeon of my hospital 

 at Bangalore, kindly submitted to be bitten by many 

 such insects in 1896. The result still remained quite 

 negative. We now know the reason : the species of 

 insect with which I was working were the wrong 

 .species. In 1907, however, I observed another variety, 

 which I called dappled-winged mosquitoes, and which 

 everyone now knows were Anophelines. I first saw 

 these in an intensely malarious quarter near Ootaca- 

 mund, where I myself acquired malaria during my 

 investigations. A few months later I obtained eight 

 of these insects in Secunderabad, and employed them 

 for my usual experiments. Six of them died or gave 

 bad dissections. 



On August 20, 1897, I '^^'as so fortunate 

 as to find in the tissues of one of these 

 insects, four days after it had been fed upon 

 a case of malaria, certain bodies which I had 

 never observed in mosquitoes before. These contained 

 the characteristic pigment of the malaria parasite. 

 Next day, August 21, I found the same bodies in the 

 last mosquito of my batch of eight — only they were 

 now larger and more definite. To those who had not 

 worked at the subject, such evidence might appear 

 slight indeed; to me, after years of toil and thought, 

 the evidence was immensely strong. A little later I 

 found the same bodies in two more mosquitoes, and 

 knew that I was on the right track ; I felt that the 

 two unknown quantities of this complex equation had 

 been simultaneously found — the species of mosquito 

 which carries malaria, and the position which the 

 parasites take in its tissues, namely, the wall of the 

 intestine. 



Now, after seventeen years, I may perhaps be 

 allowed to mention this point in order to encourage 

 those students who, as I was then, are toiling after 

 the unknown. But I at least obtained success, not 

 only by labour but also by supreme good fortune ; 

 and I believe that but for this good fortune on these 



NO. 2349, VOL. 94] 



dates, we should still have remained ignorant of the 

 manner in which malaria is conveyed, and might have 

 remained ignorant of it for the next century. Un- 

 fortunately my work was now interrupted for nearly 

 six months, just at a point when I expected to unravel 

 the whole history of the malaria parasites in a few 

 weeks ; and it was not until March of next year that 

 I was able to take up the thread again in Calcutta. 

 For manv reasons I was then unable to work at the 

 human parasites, but commenced the study of the 

 malaria parasites of birds, which are closely similar 

 to the former. In a very short time 1 was able to 

 demonstrate the presence in mosquitoes of pigmented 

 bodies derived from the allied parasites. These bodies 

 were found to grow regularly during one week after 

 the insects had" been fed, to reach maturity, and to 

 produce a number of elongated spores. Now came an 

 intensely exciting moment. What happens to these 

 spores? According to Manson 's hypothesis, they 

 ought to liberate themselves in the water in which 

 the insects died ; but I had now shown that the insects 

 did not die after two or three days, as he supposed, 

 but may live for weeks. I attempted to follow the 

 spores in all directions through the insect's tissues, 

 into the lower intestine, and even into the egg. On 

 Julv 4, 1898, however, I observed the fact that the 

 spores enter the insect's salivary or poison glands. 



The full truth was now immediately disclosed, and 

 proved to be far more wonderful than any of us had 

 ever dreamed of. The parasites are not only taken 

 from man by the mosquitoes, as Manson had supposed, 

 and are not only put into man by the mosquitoes, as 

 King had supposed, but both hypotheses are true, and 

 the insect carries the parasites directly from man to 

 man. Here then was merely another case of the great 

 law of metaxeny, which, however, was now proved for 

 the first time to hold good for protozoal parasites. 

 The malaria, like many larger parasites, require two 

 hosts for their life-cycle. 



These researches mapped out step by step every 

 detail of the transformation, and gave us a much 

 greater logical certainty than could be obtained by 

 isolated infection experiments. Nevertheless, such ex- 

 periments were attempted immediately, and in July 

 and August I infected twenty-two out of twenty-eight 

 healthy birds by the means of the bites of infected 

 Culex— thus completing the whole story in detail. 

 True, that was done with birds' malaria, and I had 

 only seen the first steps of the process with regard to 

 human malaria ; but, any zoologist will know that 

 with such closely allied species, the life-cycle of one 

 is sure to be almost exactly similar to the life-history 

 of the other — as proved to be the case here. My work 

 was now interrupted again, and for nearly a whole 

 vear ; and it was not until August, 1899, that I was 

 able to show directly that the human parasites have 

 exactlv the same development. Meantime, however, 

 Koch and Daniels had confirmed my work on birds' 

 malaria; and certain Italian workers repeated it with 

 regard to the human parasites, even to causing infec- 

 tion in healthy human beings (November, 1898), three 

 months after mv similar work with birds. 



A verv important discovery had been meantime made 

 quite independently by ISIacCallum and Opie in 

 America (1897). who showed that the bodies which 

 !\Ianson had thought were flagellated spores, were 

 really sperms. Thus the large pigmented cells which 

 I had found in mosquitoes at the same date were really 

 fertilised macrogametes. This gave a much more cor- 

 rect zoological interpretation to my phenomena ; but 

 did not otherwise disturb the history which I had 

 ascertained. 



This then was the result obtained. Let me sum- 

 marise it briefly. From the time of the Romans, we 

 were aware that the malarial fevers are connected 



