however, that the fable refers merely to the drainage of the
swamps for agricultural purposes. In Italy there was a vast
and very old system of soil-drainage by cuniculi^ probably
constructed by the Etruscans ; and some have suggested that
this drainage was carried out against malaria, and that it
enabled the ancients to build villas at spots now deadly.
Here, again, the object of the drainage was more probably
agricultural. I should like to believe that it was a sanitary
drainage, but find difficulty in doing so. Drainage against
malaria must obviously be an urban and not a rural measure.
The cost of draining all the country round Rome merely for
sanitary purposes would have depleted the sanitary budget
even of the logical ancients. Mr Jones's view appears the more
probable ā namely that the disease was possibly introduced
at the time of the first foreign expansions, both in Greece and
Italy, and that it gradually became intensified owing to the
^ See also F. Genovese [1909].
i] ANCIENT TIMES 5
causes described in sections 30 (20). North [1896] ascribes the
intensification to rural depopulation ā due to wars or to
economical changes. I think it more probable that the malaria
produced, or helped to produce, the rural depopulation ; and
we now have the living picture of the process before our eyes
in Mauritius. Possibly also the disease has always had a
tendency to eliminate or repel the fair strain of blood from
the north, leaving the darker southern strains predominant.
But the effect in Italy was probably less than in Greece,
owing to the much smaller proportion of malarious area in
the former.
Of course the Roman writers, both medical and non-medical,
were acquainted with the leading facts about paludism
mentioned above. The erudite Varro (116-28 B.C.) says in
his Renan Riisticamm, " Animadvertendum etiam si quo erunt
loca palustria, et propter easdem causas, et quod crescunt
animalia quaedam minuta, quae non possunt oculi consequi,
et per aera intus in corpus, per os ac nares perveniunt atque
difficiles efficiunt morbos" ā that in marshes there are animals
too small to be seen, but which enter the mouth and nostrils
and cause troublesome diseases. Other famous passages are
from Columella (about the first century B.C.), who says that
bogs breed insects armed with stings, and pestilent swimming
and creeping things, from which come obscure diseases. Here
we have malaria connected not only with the marsh, but
with insects or germs bred in the marsh. Cicero and Seneca
say that paludism depopulated certain districts. Mr Robert
Gladstone and Mr Jones have kindly called my attention to
several passages referring to mosquito nets, called conopeuni by
the Romans, after the Greeks (our word canopy). Herodotus
first noted with surprise the use of them in Egypt ; and they
are referred to later in Varro {^De Re Riistica 2, 10, 8), Horace
{Epodes, 9, 16), Propertius (3, 11, 45), Juvenal (6, 80), and
Paulus Silentiarius {A7tihologia Palatind). Horace says, "And
among the military standards, oh, shame ! the sun sees a
6 HISTORY [Sect.
mosquito curtain ; " and Propertius calls these nets foeda (foul
or disgraceful). Evidently the ancients felt towards them as
do many of our own more manly colonists who prefer annoy-
ance and even sickness to disgrace ! But Paulus Silentiarius
thought that they were useful for a post-prandial siesta in order
to save the slaves the trouble of using a fly-flapper. Varro
said that women, lately confined, spent a number of days in
them ; and Juvenal said that they were used to cover the
cradles of the rich and noble.
On the 6th February 1905, Sir Henry Blake, Governor
of Ceylon, called the attention of the Ceylon Branch of the
Royal Asiatic Society to the fact that certain ancient Sinhalese
writers, who lived certainly more than 1400 years ago, had
connected fever with mosquitos. The original authority
appears to be Susruta, in the chapter on Insects which forms
the last chapter of his book on Poisons. He says that there
are five kinds of mosquitos, one of which " produces the same
symptoms as deadly insects." J. Jolly, however, discussed the
subject [1905], and thinks that Susruta was merely referring
to the irritation caused by the bites. He attributed malaria,
J. Jolly says, to derangement of the humours. Personally, so
far as I can judge, I doubt whether these writers ever really
connected malaria, even in imagination, with the insects.^
2, Early Modern Times. ā Little was added to our know-
ledge during the next thousand years ; but about 1640 the
inestimable boon of Cinchona bark was introduced into Europe.
The Countess d'El Cinchon, wife of the Viceroy of Peru, had
been cured of fever by means of it in that country, where
it had been discovered by the Indians near Loxa (?) ; and she
was wise enough to send it home to Europe. The use of it,
after many checks, gradually spread ; and in 1820 Pelletier
^ I can ascertain little about malaria in early days in America ; but according to a
suggestive paper by O. Effertz, the disease was probably introduced there from
Europe, just as the converse happened with syphilis [1909].
2] EARLY MODERN TIMES 7
and Caventou extracted the alkaloid quinine from it. But
the discovery of this specific has not only proved to be a
blessing for the treatment of untold millions of human beings,
but also enabled Morton [1697] and Torti [1753] to separate
the malarial fevers, which are cured by it, from those upon
which it has no influence, and by this means to differentiate
and study the symptoms of the former. Morton also recalled
the old hypothesis of the marsh ; and this was amplified by
Lancisi, who repeated the views of Varro and Columella in
greater detail in his book De noxiis paluduni effluviis. He
stated that fevers disappear after drainage, and attributed
the poison either to inorganic or organic emanations from the
marsh. He studied mosquitos, and even suggested inoculation
by them as a possible means of infection ā though he also
thought that their larvae foul drinking water [17 17].
It is now apparent that the world had been gradually
becoming aware during centuries of the paludic nature of
malarial fever, not by direct experiment or even by investiga-
tion, but by a kind of subconscious experience based on public
observations. In Italy especially, where of all civilised countries
the disease was most prevalent, this process was most apparent
ā so much so that, as North describes [1896], the peasantry
can often tell at sight which localities are likely to be
" malarious." More than this, by similar general observation,
the good effect of assainment of marshes had become equally
notorious there. Thus, as early as 1667, Doni wrote a work
called De Restituenda Sahibj'itate Agri Romani ; and references
to a succession of works carried out on this principle, which
I now call the principle of Mosquito Reduction, are given by
Celli [1901]. At the same time efforts were made by many
observers, such as Morton, Lancisi, Lind, Pringle, to explain
the paludic connection ; and these resulted in the formation
of the hypothesis of the pahidic miasma. This was supposed
to be some kind of infecting emanation from stagnant water,
either chemical, or as Lancisi suggested, organic ; but in no
8 HISTORY [Sect.
cases, apparently, were experiments made to test the point.
Later, when it was observed that malaria may sometimes occur
where there is no marsh, the hypothesis of the paludic miasma
was extended to that of the telluric miasma, according to which
the poison exists not only in marshes but anywhere in suitable
soil, from which it rises at night or when the soil is disturbed.
This speculation, for it is nothing more, is not quite dead even
yet, though the observation which originated it is easily ex-
plained otherwise. The word " malaria " {maV aria or bad air)
is derived from it.
3. Discovery of the Parasites. ā Last century, however,
pathological science was no longer content with mere guesses
at the truth, but began to demand strict microscopical and
experimental evidence. Applied to paludism, this method gave
an early reward. In 1847, H. Meckel discovered innumerable
black granules in the blood of an insane patient ; and the
discovery was subsequently confirmed and amplified by Dlauhy,
Virchow, Heschl, Planer and Arnstein ā the granules now being
known under the name of the paludic pigmejit, or melanin, or
haematozoin (Sambon).^ For a long time they were thought
to be due to a chemical action of the paludic miasma on the
red cells of the blood.
About the same time many laborious attempts were made
to discover some animal or vegetable organism which lives in
marshes and produces paludism. As long ago as 1846 Rasori
(cited by S. Calandruccio) made an extraordinary prediction on
this subject. " For many years," he said, " I have held the
opinion that the intermittent fevers are produced by parasites
that cause the successive paroxysms of fever by their repro-
duction, which occurs periodically more or less rapidly according
to their species " ā and this has proved to be exactly true.
Many writers attributed the disease to various marsh-growing
vegetables. In 1862 Salisbury in particular, after considerable
^ I suggest the name Plasmodin, which is still more exact.
3] DISCOVERY OF THE PARASITES 9
study, blamed a kind of Pabnella; and after 1878, a number
of Italian workers, Lanzi and Terrigi, Edwin Klebs and C.
Tommasi-Crudeli, thought that they had actually incriminated
certain fungi or bacteria, which they said swarm in malarious
places, occur in the blood, produce spores before each paroxysm
of fever, and cause similar infection in animals. These findings
were even confirmed by Marchiafava and other Italians ; but
have now been completely discredited.
In 1878, however, A. Laveran commenced his studies of the
subject at Bone in Algeria, by following up the granules of
pigment, already referred to, in the blood of living patients.
He was struck by the fact that they were frequently contained
within cells possessing active amoeboid movements ; and, finally,
on the 6th November 1880, at Constantine, he detected the
microgametes issuing from the male cell. Though at the time
he did not know the nature of this phenomenon, it convinced
him that he was dealing with a living parasite of the human
red corpuscles. In fact the black granules are merely the
excrementitious matter produced by the parasites from the
substance of the red cells, and contained within their bodies,
or released in the tissues of the host.^
About the same time C. Gerhardt proved that healthy
persons can be infected by the inoculation of blood of patients
suffering from paludism [1884]. His experiments were after-
wards verified by many workers, and demonstrate (apart from
the microscopical discovery of the parasites) that the disease
is not due to any gaseous emanation from marshes, but is a
true infection by some living virus.
In 1886 and subsequently, C. Golgi, who v/as favourably
situated in Pavia for the work, showed clearly that the parasites
1 Recently R. Blanchard (Archi. de Parasitologic, vol. vii. 1903) would have us
believe that one P. F. H. Klencke had discovered the parasite of malaria before
Laveran ; but it is perfectly obvious from Klencke's drawings, given by Blanchard,
that his "parasites" are merely the usual artifacts found in fresh blood. Klencke,
moreover, was not studying malaria at all, but "vertigo." Medical literature is full of
such simulacra.
lo HISTORY [Sect.
reproduce by simultaneous sporulation ; that the febrile paroxysm
in the patient commences at the moment when these spores are
liberated (just as Rasori had divined) ; and that the parasites
of quartan and mild tertian fever are morphologically different
[1886]. A little later, Canalis, and Marchiafava and Celli dis-
covered similar facts regarding the malignant parasites, and
showed that they differ from the quartan and mild tertian
parasites ; and Marchiafava and Bignami suggested that they
are of two varieties, the malignant tertian and the quotidian.
In 1885 Danilewsky discovered similar parasites in birds and
several other animals ; and subsequently Marchiafava, Celli,
Bignami, Mannaberg and others, made many careful studies of
the parasites, and of their effects in human beings ; Romanowsky
found the proper way to stain them ; and many observers
verified these researches in various parts of the world ā the
literature amounting to some hundreds of publications,
4. Speculations regfardin^ the Mode of Infection.ā But the
question now arose ā an all-important question in connection
with the prevention of the disease ā How do these parasites
manage to effect an entry into the blood of men and animals ?
Most observers, remembering that the disease often abounds in
the neighbourhood of marshes, assumed at once that Laveran's
parasites must be capable of living in a changed form in stagnant
water ; and some actually sought them there. Thus Grassi and
Calandruccio suggested that a free living amoeba is really the
external stage of the organism. On the other hand, experiments
to infect healthy persons by water from marshes, made by
Marchiafava and Celli [1885], Marino [1890], and especially
Agenore Zeri [1890] failed entirely. Zeri gave marsh water
to nine persons to drink in doses from r5 to 3 litres a day for a
number of days. To another five persons he gave the water
by clyster ; and to sixteen by spray inhalation ā yet no paludism
followed. Like all negative results, his are not absolutely con-
clusive ā since the failure may have been due to some unforeseen
4] DISCOVERY OF METAXENY ii
condition absent from the experiments ; but his paper is too
important to have been forgotten as much as it has been.
Before describing my own Indian researches which com-
menced at this point, it is necessary to survey our general
parasitological knowledge, together with the state of thought
regarding malaria, at the time. Discoveries concerning
Laveran's bodies, which are animal and not vegetable organisms,
have a line of descent from previous discoveries concerning
animal parasitology, and not directly from bacteriology.
Many of the large animal parasites of man and animals have
been known to us from antiquity, but until the beginning of
the eighteenth century, were supposed, like other low forms of
life, to be created in each host by " spontaneous generation."
Even long after Redi (1668) proved that this hypothesis did
not hold for certain insects, it was still supposed to apply to the
parasites. Gradually, however, large numbers of the latter were
discovered, and Pallas put forward the view that they originate,
like other animals, from eggs, which escape from an infected
person or animals, and are by chance swallowed by another
host. Such a history is, in fact, quite correct for many parasites ;
but in 1790 Abildgaard made the remarkable discovery, by
experiment, that the parasites, called Bothriocephalus solidus
and Ligula, inhabit for a part of their lives certain fish, and
reach maturity only in certain water-fowl which happen to
swallow the infected fish. This appears to have been the first
found instance of the wonderful process of metaxeny,^ or change
of host. The idea was lost sight of for years until Eschricht in
1 84 1, and Steenstrup in his famous work on the alternation of
generations of Trematodes (1842), recalled it. It was finally
established for Cestodes by F. Kiichenmeister, physician to the
Duke of Saxe Meiningen, in 1851-1853, by means of direct
experimental feeding methods first used by him. Metaxenous
^ I use this word on the authority of De Bary, who employs the incorrect form
metoxenous in the above sense ā see his book on Fungi, Mycetozoa, and Bacteria.
Trans. Clarendon Press, Oxford, 1887, p. 387.
12 HISTORY [Sect.
parasites are those which spend part of their life in one kind
of animal, and the rest of it in another ā generally the early
part of their existence in one host, and the mature sexual part
of it in another host which preys upon the first one, as in the
rabbit and the dog, the mouse and the cat, swine and men, and
so on. Moreover, he proved that the eggs or young of the
mature parasites are able to pass back again into individuals
of the first species of host, from which they are again trans-
ferred to the second species of host ā and so on, ad infinitum.
This great discovery, which may almost be called the basis
of modern parasitology, was rapidly verified by Kiichenmeister
and Leukart for many parasites. At first it was applied to
those of the higher animals; but before 1858 Leukart dis-
covered that the Nematode worm, Cucullanus elegans of the
perch develops in the little aquatic Arthropod called Cyclops,
or the Water Flea. Next, perceiving the resemblance of this
worm to the famous Filaria medinensis, or Guinea Worm of
man, he suggested in the same year (1858) to the young
Russian naturalist and traveller, Fedschenko, that the latter
parasite may also pass a stage of its life in a Cyclops. The
Guinea Worm lives under the human skin, and emits its young
through an ulcer which it produces in the integument ā the
young next finding their way into water. A few months later
Fedschenko proved by experiments in Turkestan that Leukart
was right. He watched the development of the embryos in the
Cyclops ; but did not complete the cycle by infecting men from
the latter. He supposed, however, that men become infected
by accidentally swallowing infected Cyclops in drinking water.^
^ For an account of this discovery see R. Leukart, Die Menschlichen Parasiten,
1876, vol. ii. p. 704. As it is an extremely important discovery, I have been at
considerable pains to ascertain the exact dates. It will scarcely be believed, but
Leukart's complete works are difficult to obtain in this country. I am indebted to
Dr R. T. Leiper for having studied the question. The facts appear to be as follows :
In 1858 Leukart (when at Naples) suggested the idea to Fedschenko, who was then
about to proceed to the East ; but did so as a secret (?). In 1865 and 1866 Leukart
first published his account of the development of Cttcullanus in Cyclops, but merely
hints at the idea that F. medtnensis has a similar development, without mentioning
Cyclops as the possible second host. In 1869 Fedschenko seems to have returned from
4] TRANSMISSION OF FILARIAE 13
In 1868 another important case was discovered by Leukart
and Melnikoff in Leukart's laboratory. They found that the
yowngoi Dipylidimn caniniuvi {Taenia cucumerina), sl parasite of
dogs and cats, develops in the dog-louse ^ ā this being, I believe,
the first case in which a parasite of a mammal was found to
be transferable by any kind of vermin which feeds on that
mammal. The great credit due to Leukart in connection with
these discoveries has been much overlooked of late.
Filaria bancrofti^ a human parasite, was discovered in the
adult form by Bancroft in 1876, though its embryos had been
found by Demarquay in 1863 in chylous fluid, and by Lewis
in blood in 1872. In the Lancet, 12th January 1878, Cobbold
mentions a suggestion of Bancroft, dated the 20th April 1877,
that the worm (which is closely allied to F. medinenszs, and
indeed to Cucullanus) might be carried by mosquitos. In
1877, P. Manson, in Amoy, China, came to the same conclusion,
and on examining a number of mosquitos fed on a Chinaman
whose blood contained the embryos, discovered that these
develop in the tissues of the insects just as the embryos of
F. medinensis develop in Cyclops? This was the first time that
metaxeny was found to occur with any parasite between man
and mosquitos ; but Manson did not observe the development
of the embryos to a stage much more advanced than that
observed by Fedschenko in the Cyclops. He thought also that
mosquitos die on the surface of water a few days after feeding
on blood ; and that the partially developed embryos then
liberate themselves from the dead insects, and, after swimming
free in the water, are swallowed by human beings. But he
did not prove this; and indeed, in 1900, G. C. Low and S. P.
James, acting on the evident suggestions of my work on
Turkestan and to have published his paper in Russian, describing the development of
F. medinensis in Cyclops. The last, then, must be taken as the date of publication of
the discovery. Dr A. Jacobi, Leukart's biographer, can give me no further information.
^ R. Leukart, Die Menschlichen Parasilen, 1876, vol, ii. p. 704.
" P. Manson, Filaria sanguinis hominis a7id Certain New Forms of Parasitic
Diseases. London, 1883.
14 HISTORY [Sect.
malaria, made observations which lead us to think that the
embryos return to human beings through the insect's proboscis.
By his detailed studies, however, Manson has built up most of
our present knowledge on the subject of filarial disease in man.
It should be noted here that all these examples of metaxeny
apply only to the higher parasites, the Helminths or Worms,
and that in some of the cases, including those of Fedschenko
and Manson, the life-cycle had been by no means completely
ascertained ā so much so that many doubted whether the
observed development of the embryos in Cyclops and Culex
could be looked upon as a genuine stage of metaxeny. But
the bodies discovered by Laveran belong to a much lower, in
fact to the lowest, class of animals ā the Unicellular ones.
Though many organisms of this class ā amoebas, gregarines,
coccids, trypanosomes ā have been discovered in various animals,
yet up to 1889 not one of them had been proved to be
metaxenous. During this year, however, a remarkable dis-
covery was made by Theobald Smith and F. L. Kilborne in
America in connection with the disease called Texas cattle-
fever. For a long time the farmers had thought that it is
caused by certain cattle-ticks. Smith and Kilborne now showed
that the disease is due to minute parasites of the red corpuscles,
akin to the parasites of malaria but not belonging to the same
group, called Piroplasma bigeminuni ; and that they are
inoculated in some way into healthy cattle by the bites of
young ticks born from a parent tick which has fed upon a
diseased ox. This fact was conclusively proved by direct
experiment, and suggested that these Piroplasmae, which are
unicellular animals, might also be metaxenous like so many of
the higher parasites. But the observers failed in following out
microscopically the life-history of the Piroplasma in the ticks,
and therefore did not actually prove any alternate generation
in them.i
^ T. Smith and F. L. Kilborne, Investigations into the Nature, Causation and
Prevention of Texas or Southern Cattle Fever. Government Printing Office.
Washington, 1893.
4] VARIOUS HYPOTHESES 15
Meantime, however, there had been many vague conjectures
to the effect that several diseases may be produced by biting
vermin. Thus, as just mentioned, American farmers had long
thought that Texas cattle-fever is carried by cattle-ticks. Many
travellers also related that African natives ascribed a peculiar
sickness to the bites of another kind of tick ; and others said
that the deadly nagana of cattle in parts of Africa is probably
due to the bites of the tsetse fly. And similar speculations
connecting both yellow fever and malaria with mosquitos had
long been rife. Generally derided at the time, these views were
speedily forgotten ; and it is only of late that many of them
have been resuscitated and discussed as instructive relics of
the past. It will, I think, interest the reader to follow the
gradual development of our knowledge of this important subject.
I have already mentioned the curious utterances of Varro,
Columella, the ancient Sinhalese books, and of Lancisi, regard-
ing insects and fever. Nuttall [1899, p. 75] gives statements
by Lustig, Rubner, Koch and myself, to the effect that the
peasantry in Italy, Tyrol, East Africa, and Assam seemed to
have vague ideas of the same kind. Dr R. H. Kennan informs
me that he has found an old ordinance of Freetown, Sierra
Leone, dated 1812, in which the inhabitants (mostly freed
slaves) are enjoined to keep the road in front of their plots in
good condition in order to prevent the formation of " stagnant
pools which generate disease and mosquitos over the town."
In 18^, Dr Josiah Nott, of Mobile, Alabama, appears to have
stated that both yellow fever and malaria may be transmitted
by mosquitos, and refers to the speculation as having been
already advanced as regards malaria. In 1854, however, Louis-