Researches on malaria Nobel Lecture, December, 12, 1902

first

44

. I 

 

have already shown in sections 11

 

and 12 how useless it is to attempt

to identify the malaria-bearing species by its preponderance in malarious

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

99

places; and it has now been demonstrated that even in Italy there is no such rela-

tion between the disease and its agent. Anopheles abound where there is no

malaria - even round Liverpool. Needless to say then, two out of the three

species isolated by Grassi have nothing to do with the disease. He was right

regarding the third, A. claviger; but it is quite reasonable to suppose that he

detached this simply from my description of the dappled-winged mosquitoes.

As a matter of fact all these epidemiological efforts of Grassi, though interest-

ing in a small way, were nothing but a series of vague speculations.*

Meantime Bignami, after four year’s inaction, had returned to his old meth-

od of attempting to infect men by the bites of mosquitoes brought from mala-

rious places. His results are minutely recorded in his paper

48

. He set to work in

August - that is, after Manson had proclaimed at the British Medical Associa-

tion that I had succeeded in infecting birds by the bites of mosquitoes

43

. Big-

nami’s task was now vastly simplified; with the guidance of my work he

collected his mosquitoes from infected houses; whereas if he had continued to

act in accordance with his own theory he would have collected them from

marshes - which would have led to constant failure (section 13). He claimed

his first success early in November, but still could not say which of the various

kinds of mosquitoes employed by him had produced the result.**

Up to November therefore the Italians had failed either to find the guilty

species of mosquito or to demonstrate the life-cycle of the parasite in the in-

sects. At this point Charles’s series of eight letters addressed from Rome to me

(dated from the 4th November to the 14th January) commence. They have

been printed by me with his consent; and show clearly (what however can be

also demonstrated from their own writings) that the Italians were then inti-

mately acquainted with my work; that they had received my report

42 

giving

full details of technique: and that they had detected the genus of my grey mos-

quitoes (from specimens sent by Manson) and of my dappled-winged mos-

quitoes (from my description). In his letter of the 8th November, 1898, Man-

* The writers of some zoological text-books, who have evidently had little personal ex-

perience of the disease, seem to have actually believed that Grassi determined the "Ano-

pheles 

malariferi" by these efforts. That is not the case. In an early work

54

 I said that they

were made independently of Manson and myself; but this was written before I

 

studied

the Italian work with close attention; and since then I have withdrawn the statement

72

.

** That human malaria is conveyed by the bites of mosquitoes had of course been proved

- practically to a certainty - by my infection of numerous birds three months previously.

Bignami’s experiment was merely a formality of which the success could already be fore-

told with confidence. The statement, frequently made, that he was the first to give exper-

imental demonstration of this fact may be set aside without comment.

100 

  1 9 0 2  R.R OS S

son records having sent some of my preparations to Charles and Bignami (on

or before that date); and Charles in his letter of the 25th November records

showing one of these to Grassi (on or before that date). It is possible, however,

that the Italians had seen my preparations long before this, as numbers of them

had been sent to Manson and Laveran in the spring and summer; and they may

also have seen those of Koch, who had cultivated Proteosoma in Rome in Sep-

tember.

Bignami, Bastianelli, and Grassi had now evidently determined to resort to

the correct method for determining the guilty species of mosquito, and imi-

tated exactly the experiment by which I had ascertained the second host of

Proteosoma 

in the previous March. The experiment was recorded by them on

the 28th November

51

. They fed six Culex pipiens, one Anopheles nigripes and

four Anopheles claviger on some cases of crescents, and at last found my pig-

mented cells in two of the last species. They do not record the exact date on

which this observation was made, but from Charles’s letters it would appear

to have been on the 25th November or later.

This, if correct, was the first definite demonstration of the guilty species of

mosquito in Italy. It was made fifteen months after my original demonstration

of the same parasite in the same genus of mosquitoes in Secunderabad on the

20th August, 1897

38

, and nearly four months after Manson had announced the

whole life-cycle of Proteosoma at the British Medical Association

43

. The Italian

experiment was, however, of doubtful correctness, because the authors do not

state that the mosquitoes used by them had been bred from the larvae

51

. At the

same time they actually impute to me the very fault which they themselves

were committing, and do so contrary to the printed evidence of my own

words.*

In their next paper

53

they claim to have found the various developmental

stages of the aestivo-autumnal parasites in A. claviger caught in houses and

stables, or fed on patients in hospital. Here again, examination of the publica-

tion shows that none of the insects employed seem to have been bred from the

larvae; and, what is still more important, the number of insects on which the

observations were made is not exactly given. For all we know, the whole

paper may have been written on the strength of only a very few positive re-

sults; and this is the more possible because it describes a life-cycle which is an

* They say that my experiment was doubtful because my mosquitoes may have previ-

ously bitten other animals

51

. Now it is clearly stated in my publications* that the insects

used by me had been bred in "bottles from the larvae"; and from the whole tenor of my

researches it was evident that such was the case.

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

101

exact repetition of that of Proteosoma. The authors give no precise differential

experiments in order to prove the connection between the pigmented cells

seen by them and the haematozoa. For this proof they rely upon my Proteosoma

report

42

, to which, however, they scarcely refer. Although their paper gives

to the ignorant the impression of being original, it is in reality merely a re-

script of mine.

Meanwhile Bignami and Bastianelli had been continuing their attempts to

infect men by A. claviger taken from houses; and claimed a second positive re-

sult early in December. In this case, however, by good fortune, the infection

proved to be a mild tertian one. Some months later, these two authors pub-

lished a paper

56 

recording the development of this parasite also in Anopheles.

This was the first, and, indeed, only important Italian result which had not

been previously indicated by me; I had made no observation connecting the

tertian parasite also with the dappled-winged mosquitoes.

Subsequently the same authors and Grassi claimed to have demonstrated

the development of the parasites in Anopheles nigripes, A. bifurcatus, and A. su-

perpictus.

They also claimed to have shown that the members of the old genus Culex

do not carry malaria; but this had long previously been abundantly proved by

me in India, at least with regard to the aestivo-autumnal parasite; and the fact

is that Grassi had only identified my grey mosquitoes, which I had shown to

be negative to this parasite. Their first drawings of the parasites in mosquitoes

were not published until the spring.*

In my first reference to the Italian work I accepted it with some reserve; but

after a careful examination of their writings made in 1900 I felt much more

scepticism. Their work during the winter of 1898-1899 is evidently hasty and

deficient in exact details regarding the various observations; and the general

tenor of their historical passages is so inaccurate as to inspire grave doubts re-

garding the whole literature. I think that at that time they found my pigment-

ed cells in a few, possibly a very few, A. claviger and that Bignami and Bastia-

nelli also showed that the tertian parasite develops in the same insects; but

beyond this it is impossible to speak with confidence. Many of their details

also are derived from me.

My work was completed in the autumn of 1899 at Sierra Leone (section

22) and was published immediately

6 0

. Many of the details are incorporated in

* For an independent account of all these researches the detailed history of Nuttall

65 

and

especially his critique on the priority question

74

, should be consulted.

See also

72,73,76

.

102 

    1 9 0 2   R.R O S S

Grassi’s book published in June next year

69

. This work, which is dedicated to

Manson, is principally a compilation of the researches of others - the historical

passages being quite inaccurate. At the bottom of page 31 of the first edition,

the author says, "Giova infine far risaltare the io arrivai agli Anopheles mala-

riferi independentemente da Ross, le cui ricerche sui parassiti malarici degli

uccelli furono pubblicate quasi contemporaneamente alla mia prima Nota

preliminare." He and his colleagues found the "Anopheles malariferi" in Italy

by detecting the genus of my dappled-winged mosquitoes; but they did not

incriminate it with certainty until the end of November, five months after

Manson published my work on the malaria of birds

41

. Grassi’s "first prelimi-

nary note"

44 

was published more than three months after this paper of Man-

son’s, and, moreover, refers to my work as a well-known matter even then. I

found the "Anopheles malariferi" in two species of mosquito in India fifteen

months 

before Bastianelli, Bignami, and Grassi found it in Italy. Speaking

quite strictly and accurately it is the principal merit of Grassi to have discov-

ered, not the "Anopheles malariferi", but its correct entomological name.*

Excepting the discovery of the host of the tertian and perhaps the quartan

parasites, the Italian work was simply a local affair, done, like the work of my

colleagues and myself in Sierra Leone and of other observers in many parts of

the world, on the basis of my Indian researches culminating in July 1898 (sec-

tion 17).

Of the sixteen and more species of Anopheles which have now been definite-

ly connected with malaria, only three or four were incriminated by the Ital-

ians; it is therefore quite incorrect to attribute the determination of this rela-

tion to them - much more to attribute it, as some have done, to Grassi alone.

The connection between Anopheles and malaria has been determined by the

united efforts of many observers in many parts of the world.

*Early in 1903 this writer published a pamphlet purporting to be a translation of impor-

tant papers on the subject (Documenti riguardanti la storia della scoperta del mode di transmis-

sione della malaria umana; 

Milano). It contains no bibliography nor accurate history of the

events; and omits most of the principal publications of my work. It purports to give in

full my paper recording the original discovery of the pigmented cells

38

; but on exam-

ining this copy I find that the drawings of the cells given by Manson, and the remarks of

Manson, Bland Sutton, and Thin (all of which, of course, absolutely establish the genu-

ineness of the discovery) are omitted without the smallest explanation. The author then

proceeds to claim the discovery for himself. This work also is dedicated to Manson - a fact

which may lead many to believe in its accuracy; but Manson has publicly stated that it

was dedicated to him without his permission (Lancet and British Medical ]ournal, 28th

March, 1903).

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103

(3) Certainly not less important than the Italian work has been that of the

Malaria Commission of the Royal Society, consisting of Drs. Daniels, Steph-

ens, and Christophers. After confirming my results in Calcutta as mentioned

in section 20, Dr. Daniels proceeded to British Central Africa, where he met

Drs. Christophers and Stephens, who had proceeded there after a month’s stay

in Italy in the autumn. These observers had great trouble at first in obtaining

suitable cases for experiment, but finally succeeded in doing so. Daniels con-

firmed our results in Sierra Leone, and added many useful and interesting de-

tails. Stephens and Christophers afterwards followed us in Sierra Leone and

elsewhere in West Africa, and then proceeded to India.

The researches of all these gentlemen are given in the admirable reports to

the Malaria Committee of the Royal Society

7 1

. These researches have had the

effect of completely consolidating previous work on the subject. The authors

have shown no less than eight species of Anopheles to be amenable to the ma-

laria infection, and that Culices and Stegomyiae are always refractory; they

have demonstrated many of the habits of these insects in various parts of the

world; and, besides, have given us much invaluable information regarding

the pathology of the disease, especially of blackwater fever. Stephens and

Christophers also found independently the great law of Koch regarding the

prevalence of malaria amongst native children in the tropics.

The perusal of the writings of these gentlemen and of many other observers

will convince any one that it is impossible to do justice to them in the form of a

brief review; it is scarcely even fair to attempt to describe such laborious

work in a few words; and I shall therefore now draw this lecture to a close

with the remark, that I hope soon to deal with all these investigations in a

manner which is due to them. But I should like to conclude with the names of

a few of those who have more recently added valuable information to our

store of knowledge regarding the mosquito theory of malaria - particularly

Ziemann, Manson, T. Manson, the members of the numerous expeditions of

the Liverpool School of Tropical Medicine (Drs. Fielding-Ould, Annett,

Dutton, Elliott, Logan Taylor), Fernside, James, Low, Sambon, Van der

Scheer, Van Berlekom, Celli, Nuttall, Shipley, Ruge, Howard, Theobald,

Schaudinn, and Sir William MacGregor. I omit to refer to their works, and

those of many others, only because it is impossible to do so properly within

the limits of this work.

It would not be right, however, to conclude without referring to those most

conspicuous examples of the success of anti-malaria measures for the improve-

ment of public health - the cases of Havana and Ismailia. A campaign against

104

   1 9 0 2  R .RO S S

yellow fever and malaria was commenced at Havana early in 1901; and Colo-

nel and Assistant Surgeon General Gorgas of the United States Army, who

was in charge of the work, has recently reported as follows on the success of it,

in a lecture delivered on May 22nd at the New York Post Graduate Clinical

Society.

"The results of these combined measures were very marked. Mosquitoes

entirely disappeared from many parts of the city, and were decreased every-

where. On the first inspection made in January, 1901, 26,000 collections of

fresh water were found in the city, containing mosquito larvae, this exclusive

of the cess-pools. In January 1902, the consolidated inspection reports cover-

ing the same area, showed less than 300; but the most striking evidence was its

results on yellow fever. It must be borne in mind that yellow fever had been

constantly in Havana since 1760, that it was not, as it had been in our North

American cities, some years present and some years absent, but steadily every

year and every month and every day, in all that time. The deaths from yellow

fever had been since 1889, about as follows: 303 (1890); 364 (1891); 352

(1892); 482 (1893); 388 (1894); 549 (1895); 1355 (1896); 743 (1897); 127

(1898); 118 (1899); 301 (1900)     

 ; in 

1901, the first year of our mosquito work

5, and since September 1901, not a single case.

The work with regard to malaria is not quite so striking, and this necessarily

follows from the nature of the disease. But I think the results, as shown by the

Table 2. Statistics of malaria at Ismailia.*

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105

sanitary reports, are very hopeful, with regard to malaria, and indicate that in

the course of time, malaria can be also eradicated. In 1900, the year before mos-

quito work, the deaths from malaria were 344; in 1901, the first year of mos-

quito work, they had fallen to 151; in 1902, the second year of mosquito

work, they had dropped to 90, and, for the first four months of 1903, 16."

At the end of 1902, the Suez Canal Company asked me to go to Ismailia on

the Suez Canal, in order to advise regarding the best measures to take against

the malaria which had long been prevalent in that town. I advised active oper-

ations against the mosquitoes; and this advice was followed with great ener-

gy and success. The table of statistics (Table 2), kindly supplied by Prince

D’Arenberg, the President of the Company, speaks for itself.

Not only, however, from this place do we hear of reduction of sickness and

mortality. Undoubtedly the whole West Coast of Africa is much improved,

and good accounts continue to flow in from Lagos, the Gold Coast, British

Central Africa, Hongkong, and further India; and it is to be hoped that within

a few years malaria will, as Sir William MacGregor says, have lost its terrors,

at least for Europeans who are called upon to serve in the tropics.

This list of works, chronologically arranged, includes chiefly my own writings, many of

which are omitted in bibliographies, and such others as are referred to in the text.

1. Manson, On the Development of Filaria Sanguinis Hominis and on the Mosquito Consid-

ered as a Nurse, 

Linnean Society, 1878. Also Trans. Pathol. Soc., 32 (1881).

2. King, "Insects and disease, mosquitoes and malaria.", Popular Sci. Monthly, Sep.

(1883).

3. Laveran, Traité des Fièvres Palustres, Paris, 1884, p. 457.

4. Celli and Marchiafava, Fortschr. Med., (1885).

5. Macloskie, "The poison apparatus of the mosquito.", Am. Naturalist, 1888.

6. Lewis, Physiological and Pathological Researches, Lewis Mem. Comm., London, 1888,

p. 638.

7. Agenore, "Acqua potabile e malaria.", Atti Accad. Med. Roma, 5 (1890).

8. Marino, "Dell’ acqua dei luoghi malarici.", Riforma Med., (1890).

9. Grassi and Feletti, Several papers, Zentr. Bakteriol., 

9 

(1891).

10. Grassi and Feletti, "Contribuzione allo studio dei parassiti malarici.", Atti Accad. Gioe-

nia

 Sci. Nat. Catania, 5, Ser. 4a.

11. Laveran, Du Paludisme et de son  Hématozoaire, Paris, 1891, p. 147.

12. Ross, "Fever with intestinal lesions.", Trans. South Indian Branch, Brit. Med. Assoc.,

1892.

13. Ross, "Cases of febricula with abdominal tenderness.", Indian Med. Gaz., (1892) 166.

106

    1 9 0 2   R.R OS S

14. Ross, "Entero-septic fevers.", Indian Med. Gaz., (1892) 230.

15. Ross, "A study of Indian fevers.", Indian Med. Gaz., (1892) 290.

16. Ross, "Some observations on haematozoic theories of malaria.", Med. Reporter (after-

wards Indian Lancet), 

(1893) 65.

17. Ross, "Nodulated and vacuolated corpuscles.", Indian Med. Record, (1893) 213.

18. Ross, "Solution of corpuscles mistaken for parasites.", Indian Med. Record, (1893) 310.

19. Smith and Kilborne, Investigations into  the Nature, Causation and Prevention of  Texas or

Southern Cattle Fever, 

Bull. No. 1, Bur. Animal Ind., U.S. Dept. Agr., 1893. Also see

Zentr. Bakteriol., 

(1893).

20. Ross, "Third element of the blood and the malaria parasite.", Indian Med. Gaz., Jan.

(1894) 5.

21. Ross, 

"A 

list of natural appearances in the blood which have been mistaken for forms

of the malaria parasite.", Indian Med. Gaz., Dec. (1894) 441.

22. Manson, "On the nature and significance of the crescentic and flagellated bodies in

malarial blood.", Brit. Med. J., Dec. 8 (1894).

23. Sacharoff, "Über die selbständige Bewegung der Chromosomen bei Malaria Parasi-

ten." Zentr. Bakteriol., (1895).

24. Ross, "Observations on the crescent-sphere flagella metamorphosis of the malarial

parasite within the mosquito.", Trans. South Indian Branch, Brit. Med. Assoc., Dec.

(1895). Also Indian Lancet, (1896) 227, 259.

25. Ross, "Observations on malaria parasites made in Secunderabad, Deccan.", Brit.